Addiction Medicine

How many providers does it take to depersonalize a patient? Nine? 1. A psychiatrist for transcranial magnetic stimulation (TMS). 2. A psychiatrist for ketamine. 3. A psychiatrist who specializes in substance use disorder medication. 4. A psychiatrist for the rest of the psychotropic medication. 5. An alternative medicine provider who prescribes supplements. 6. A therapist for depression who uses cognitive-behavioral therapy. 7. A therapist for posttraumatic stress disorder who uses eye movement desensitization and reprocessing. 8. An addiction counselor. 9. An equine therapist.

This doesn’t include other providers and professionals who likely contribute to one’s mental well-being, including yoga instructors and personal trainers. In addition, any one of those psychiatrists may have one or more nurse practitioners who routinely step in to attend to appointments.

In our uncertain and lonely times, the value of human contact and interaction has become exponentially more precious. I long to see my patients in my private practice office. I am now much more aware of their grounding effect on my life, and I suspect I had a similar grounding effect on theirs. Few things provide me more comfort than sitting on my lounge chair with a curious gaze waiting for the patient to start the visit. I often wonder what makes a patient choose to go see a private practice physician. Yet a common reason offered is, “Wait! You do everything? Therapy and meds if I need them? You’ll see me every week?”

While I am realistic about the need and use of split-care, I have never been enamored with the concept. I think that few medical students choose psychiatry with the goal of referring all psychotherapeutic needs and intervention to “allied mental health providers” as my prior managed care organization liked to refer to psychologists, social workers, marriage and family therapists, and other counselors. I remember particularly as a chief resident being bombarded by complaints of therapists complaining about psychiatry residents. All of their patients’ symptoms allegedly required medication adjustment and residents were supposedly dismissing them. In return, residents would complain that the therapists did not address the psychological manifestations of the patient’s ailments. Herein lies my problem with split-care, it encourages psychotherapy to be about medication management, and medication management to be about psychotherapy.

However, this is not an article against split-treatment. Psychiatrists, for a variety of reasons, are not suited to perform psychotherapy in most management care models. The main reason being that psychiatrists’ time is too expensive to justify the expense, and psychiatrists are (for the most part), the only ones able to prescribe medications for which the wait-list is already long enough. This article is about the absurd levels at which we have fragmented care of certain patients. Split-treatment is relevant in that its negative side effects, we are almost all familiar with, exemplify the problem of the fragmentation of modern psychiatry. In many ways this fragmentation of care is similar to polypharmacy – the premise for each psychotropic intervention may be sound, but the end result is often incoherent.

My main concern with the fragmentation of modern psychiatry stems from my belief that the most important facet of our work is our relationship with our patients. It is the duty we owe them, the attention we give them, the unique nature of interactions. Who among the nine providers is responsible for writing a discharge summary? Who is responsible for calling an emergency contact in a critical situation? Who communicates with the new provider when someone is taken off an insurance panel? Who makes the patient feel cared for? I am often confronted by this situation when TMS or ketamine providers say, “I just give the procedure/medication that was ordered by the referring psychiatrist.” This response disturbs me in that I could not imagine myself being so hands off in the care of a patient. There is an implication of projected immunity and lack of responsibility that bothers me.

But my concerns are also practical. From my forensic experience, I am well aware that the larger the number of providers treating a patient, the larger the number of inconsistent diagnoses, the more likely medication reconciliations are not kept up to date or incorrect, and the more likely intervention recommendations are contrary to one another. A disengaged ketamine provider may not realize that the patient was more recently enrolled in a substance use disorder program, a potential contraindication for ketamine, if not well-abreast of the patient’s continued evolution. A disengaged therapist may not realize that a patient appears unmotivated because of an increasing dose of medication rather than poor effort. A substance use disorder psychiatric specialist may be at odds with a substance use disorder counselor who worries about the message of treating psychiatric symptoms with chemical substances if they don’t communicate.

As with polypharmacy, “polydoctoring” has negative effects. While the field of psychiatry’s advancing knowledge may encourage providers to specialize, patients still desire and benefit from an intimate and close relationship with one provider who is warm, concerned, and hopeful. Those traits can theoretically be provided by anyone and there is not something inherently wrong with having more than one provider. However, psychiatry would be wise to recognize this concerning trend, especially at a time when we all feel lonely, disconnected, and depersonalized.
 

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com.

How many providers does it take to depersonalize a patient? Nine? 1. A psychiatrist for transcranial magnetic stimulation (TMS). 2. A psychiatrist for ketamine. 3. A psychiatrist who specializes in substance use disorder medication. 4. A psychiatrist for the rest of the psychotropic medication. 5. An alternative medicine provider who prescribes supplements. 6. A therapist for depression who uses cognitive-behavioral therapy. 7. A therapist for posttraumatic stress disorder who uses eye movement desensitization and reprocessing. 8. An addiction counselor. 9. An equine therapist.

This doesn’t include other providers and professionals who likely contribute to one’s mental well-being, including yoga instructors and personal trainers. In addition, any one of those psychiatrists may have one or more nurse practitioners who routinely step in to attend to appointments.

In our uncertain and lonely times, the value of human contact and interaction has become exponentially more precious. I long to see my patients in my private practice office. I am now much more aware of their grounding effect on my life, and I suspect I had a similar grounding effect on theirs. Few things provide me more comfort than sitting on my lounge chair with a curious gaze waiting for the patient to start the visit. I often wonder what makes a patient choose to go see a private practice physician. Yet a common reason offered is, “Wait! You do everything? Therapy and meds if I need them? You’ll see me every week?”

While I am realistic about the need and use of split-care, I have never been enamored with the concept. I think that few medical students choose psychiatry with the goal of referring all psychotherapeutic needs and intervention to “allied mental health providers” as my prior managed care organization liked to refer to psychologists, social workers, marriage and family therapists, and other counselors. I remember particularly as a chief resident being bombarded by complaints of therapists complaining about psychiatry residents. All of their patients’ symptoms allegedly required medication adjustment and residents were supposedly dismissing them. In return, residents would complain that the therapists did not address the psychological manifestations of the patient’s ailments. Herein lies my problem with split-care, it encourages psychotherapy to be about medication management, and medication management to be about psychotherapy.

However, this is not an article against split-treatment. Psychiatrists, for a variety of reasons, are not suited to perform psychotherapy in most management care models. The main reason being that psychiatrists’ time is too expensive to justify the expense, and psychiatrists are (for the most part), the only ones able to prescribe medications for which the wait-list is already long enough. This article is about the absurd levels at which we have fragmented care of certain patients. Split-treatment is relevant in that its negative side effects, we are almost all familiar with, exemplify the problem of the fragmentation of modern psychiatry. In many ways this fragmentation of care is similar to polypharmacy – the premise for each psychotropic intervention may be sound, but the end result is often incoherent.

My main concern with the fragmentation of modern psychiatry stems from my belief that the most important facet of our work is our relationship with our patients. It is the duty we owe them, the attention we give them, the unique nature of interactions. Who among the nine providers is responsible for writing a discharge summary? Who is responsible for calling an emergency contact in a critical situation? Who communicates with the new provider when someone is taken off an insurance panel? Who makes the patient feel cared for? I am often confronted by this situation when TMS or ketamine providers say, “I just give the procedure/medication that was ordered by the referring psychiatrist.” This response disturbs me in that I could not imagine myself being so hands off in the care of a patient. There is an implication of projected immunity and lack of responsibility that bothers me.

But my concerns are also practical. From my forensic experience, I am well aware that the larger the number of providers treating a patient, the larger the number of inconsistent diagnoses, the more likely medication reconciliations are not kept up to date or incorrect, and the more likely intervention recommendations are contrary to one another. A disengaged ketamine provider may not realize that the patient was more recently enrolled in a substance use disorder program, a potential contraindication for ketamine, if not well-abreast of the patient’s continued evolution. A disengaged therapist may not realize that a patient appears unmotivated because of an increasing dose of medication rather than poor effort. A substance use disorder psychiatric specialist may be at odds with a substance use disorder counselor who worries about the message of treating psychiatric symptoms with chemical substances if they don’t communicate.

As with polypharmacy, “polydoctoring” has negative effects. While the field of psychiatry’s advancing knowledge may encourage providers to specialize, patients still desire and benefit from an intimate and close relationship with one provider who is warm, concerned, and hopeful. Those traits can theoretically be provided by anyone and there is not something inherently wrong with having more than one provider. However, psychiatry would be wise to recognize this concerning trend, especially at a time when we all feel lonely, disconnected, and depersonalized.
 

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com.

How many providers does it take to depersonalize a patient? Nine? 1. A psychiatrist for transcranial magnetic stimulation (TMS). 2. A psychiatrist for ketamine. 3. A psychiatrist who specializes in substance use disorder medication. 4. A psychiatrist for the rest of the psychotropic medication. 5. An alternative medicine provider who prescribes supplements. 6. A therapist for depression who uses cognitive-behavioral therapy. 7. A therapist for posttraumatic stress disorder who uses eye movement desensitization and reprocessing. 8. An addiction counselor. 9. An equine therapist.

This doesn’t include other providers and professionals who likely contribute to one’s mental well-being, including yoga instructors and personal trainers. In addition, any one of those psychiatrists may have one or more nurse practitioners who routinely step in to attend to appointments.

In our uncertain and lonely times, the value of human contact and interaction has become exponentially more precious. I long to see my patients in my private practice office. I am now much more aware of their grounding effect on my life, and I suspect I had a similar grounding effect on theirs. Few things provide me more comfort than sitting on my lounge chair with a curious gaze waiting for the patient to start the visit. I often wonder what makes a patient choose to go see a private practice physician. Yet a common reason offered is, “Wait! You do everything? Therapy and meds if I need them? You’ll see me every week?”

While I am realistic about the need and use of split-care, I have never been enamored with the concept. I think that few medical students choose psychiatry with the goal of referring all psychotherapeutic needs and intervention to “allied mental health providers” as my prior managed care organization liked to refer to psychologists, social workers, marriage and family therapists, and other counselors. I remember particularly as a chief resident being bombarded by complaints of therapists complaining about psychiatry residents. All of their patients’ symptoms allegedly required medication adjustment and residents were supposedly dismissing them. In return, residents would complain that the therapists did not address the psychological manifestations of the patient’s ailments. Herein lies my problem with split-care, it encourages psychotherapy to be about medication management, and medication management to be about psychotherapy.

However, this is not an article against split-treatment. Psychiatrists, for a variety of reasons, are not suited to perform psychotherapy in most management care models. The main reason being that psychiatrists’ time is too expensive to justify the expense, and psychiatrists are (for the most part), the only ones able to prescribe medications for which the wait-list is already long enough. This article is about the absurd levels at which we have fragmented care of certain patients. Split-treatment is relevant in that its negative side effects, we are almost all familiar with, exemplify the problem of the fragmentation of modern psychiatry. In many ways this fragmentation of care is similar to polypharmacy – the premise for each psychotropic intervention may be sound, but the end result is often incoherent.

My main concern with the fragmentation of modern psychiatry stems from my belief that the most important facet of our work is our relationship with our patients. It is the duty we owe them, the attention we give them, the unique nature of interactions. Who among the nine providers is responsible for writing a discharge summary? Who is responsible for calling an emergency contact in a critical situation? Who communicates with the new provider when someone is taken off an insurance panel? Who makes the patient feel cared for? I am often confronted by this situation when TMS or ketamine providers say, “I just give the procedure/medication that was ordered by the referring psychiatrist.” This response disturbs me in that I could not imagine myself being so hands off in the care of a patient. There is an implication of projected immunity and lack of responsibility that bothers me.

But my concerns are also practical. From my forensic experience, I am well aware that the larger the number of providers treating a patient, the larger the number of inconsistent diagnoses, the more likely medication reconciliations are not kept up to date or incorrect, and the more likely intervention recommendations are contrary to one another. A disengaged ketamine provider may not realize that the patient was more recently enrolled in a substance use disorder program, a potential contraindication for ketamine, if not well-abreast of the patient’s continued evolution. A disengaged therapist may not realize that a patient appears unmotivated because of an increasing dose of medication rather than poor effort. A substance use disorder psychiatric specialist may be at odds with a substance use disorder counselor who worries about the message of treating psychiatric symptoms with chemical substances if they don’t communicate.

As with polypharmacy, “polydoctoring” has negative effects. While the field of psychiatry’s advancing knowledge may encourage providers to specialize, patients still desire and benefit from an intimate and close relationship with one provider who is warm, concerned, and hopeful. Those traits can theoretically be provided by anyone and there is not something inherently wrong with having more than one provider. However, psychiatry would be wise to recognize this concerning trend, especially at a time when we all feel lonely, disconnected, and depersonalized.
 

Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com.

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Heavy alcohol use in adolescence is linked to disruptions in white-matter integrity, new research suggests.

Highwaystarz-Photography/Thinkstock

In a case-control study of more than 400 participants, the association was more pronounced in younger adolescents and in the anterior and middle corpus callosum, which serve the interhemispheric integration of frontal networking and communication.

The results provide clinicians with yet another reason to ask adolescents about their alcohol use, said investigator Adolf Pfefferbaum, MD, Center for Health Sciences, SRI International, Menlo Park, Calif., and professor emeritus at Stanford (Calif.) University.

However, when questioning adolescents about their alcohol use, “sometimes it’s better to ask: ‘How much alcohol do you drink?’ ” instead of just asking if they drink, Dr. Pfefferbaum said in an interview. That’s because they may be more willing to answer the first question honestly.

It’s also important for clinicians to nonjudgmentally tell teens there is evidence “that heavy drinking is bad for their brain,” he added.

The findings were published online Dec. 30, 2020, in JAMA Psychiatry.
 

Fractional anisotropy

Adolescence is a critical period of physiological and social maturation accompanied by significant structural, functional, and neurochemical brain changes, the investigators noted.

Diffusion tensor imaging (DTI) produces a measure called fractional anisotropy (FA), which characterizes some of these brain changes by measuring molecular water diffusion in the brain.

“FA is a measure of the integrity of brain white matter; so, the part of the brain that connects neurons with each other,” Dr. Pfefferbaum said. He added that FA decreases in diseases such as multiple sclerosis (MS), reflecting “some kind of pathology.”

Affected fiber systems include the corpus callosum, superior longitudinal fasciculus, internal and external capsule, brain stem, and cortical projection fibers. Disruption of these neural systems may degrade neural signal transmission and affect certain cognitive functions, possibly resulting in enhanced impulsivity, poor inhibitory control, and restricted working memory capacity, the researchers wrote.

FA follows an inverted U-shaped pattern. “The natural trajectory is to increase from infancy up to middle adolescence and then, as we get older, from about age 25 to 30 years, starts to go down. Our brains are starting to show signs of aging a bit by then,” said Dr. Pfefferbaum.

The current analysis assessed 451 adolescents (228 boys and 223 girls) from the NCANDA study, for whom researchers had four years of longitudinal DTI data. All were aged 12- 21 years at baseline.

The NCANDA cohort was recruited across five U.S. sites. Participants are assessed yearly on psychobiologic measures, including brain maturation. The cohort, which did not have any significant substance abuse upon entry, is balanced in terms of gender and ethnicity.

The investigators quantified the developmental change of white-matter (WM) integrity within each individual as the slope of FA over visits. They also examined altered developmental trajectories associated with drinking onset during adolescence and the differential alcohol associations by age with specific regional WM fiber tracts.

Researchers assessed drinking on a scale of 1-4, based on the youth-adjusted Cahalan score. The scale considers quantity and frequency to classify drinking levels based on past-year self-reported patterns.
 

Altered trajectory

Results showed that 291 participants (37.2%) remained at no to low drinking levels (youth-adjusted Cahalan score, 0) throughout the time points examined, and 160 (20.5%) were classified as heavy drinkers for at least two consecutive visits (youth-adjusted Cahalan score >1).

Among the no to low drinkers, 48.4% were boys with a mean age of 16.5 years and 51.2% were girls with a mean age of 16.5 years. About two thirds of the group (66%) were White.

Among heavy drinkers, 53.8% were boys with a mean age of 20.1 years and 46.3% were girls with a mean age of 20.5 years. In this group, 88.8% were White.

The investigators did not analyze moderate drinkers or those who initiated heavy drinking for only one visit.

The findings also showed that heavy drinkers exhibited significant reduction of whole-brain FA. The slopes of the 78 heavy drinkers were significantly more negative than the 78 matched no to low drinkers (mean, –0.0013 vs. 0.0001; P = .008).

“The concept of the slopes is really important here because it’s the trajectory that seems to be the most sensitive measure,” Dr. Pfefferbaum said. “Probably what’s happening is the exposure to alcohol is interfering with the normal myelination and normal development of the adolescent’s white matter.”

The no to low drinkers had relatively stable FA measures across all visits.

A reduction in FA was significantly linked to heavy drinking. An analysis of 63 youth who transitioned from being a no to low drinker to a heavy drinker showed that before the transition, they had significantly increased FA over visits (95% CI of slope, 0.0011-0.0024; P < .001). In addition, their corresponding slopes were not different from other no to low drinkers of the same age range.

However, this group’s FA declined significantly after they reported heavy drinking, resulting in slopes significantly below zero (95% CI of slope, –0.0036 to –0.0014; P < .001) and that were lower than the no to low participants of the same age range.

The findings of this unique before-and-after assessment “bring us one step closer to causality,” and further illustrates that heavy drinking in adolescence affects WM integrity, Dr. Pfefferbaum said.
 

Potential markers

None of the slope measures correlated with number of visits or use of tobacco or cannabis. The association of alcohol with the slope measures was more apparent in the younger cohort (<19 years).

“The effects were seen more readily in younger adolescents because they are the ones who are still progressing along this normal developmental trajectory,” Dr. Pfefferbaum noted. “In a sense, the younger you are when you’re exposed to alcohol, probably the more vulnerable you are.”

Previous studies have suggested that damage in WM tracts is associated with heightened neural reactivity to alcohol cues in adults with alcohol use disorder. Given this evidence, the greater WM degradation at younger versus older ages might help explain why adolescents who initiate early drinking are more likely to develop addiction later in life, the investigators wrote.

Of the five major fiber tracts, only the commissural fibers (corpus callosum) showed a significant association with alcohol. The researchers noted that WM volume shrinkage and callosal demyelination are two of the most prominent markers in adult alcoholism and are potential markers in adolescent alcohol abuse.

Upon further extending the analysis to the four subregions of the corpus callosum, the investigators found that only the anterior and middle callosal regions (genu and body) showed significant age-alcohol interactions.

This could be a result of the timing of fiber myelination in these regions of the brain, compared with others, Dr. Pfefferbaum said.

He noted that these fibers connect the left and right part of the anterior regions of the brain, especially the frontal lobes, which are particularly vulnerable to the effects of alcohol. “It may well be that we have this interaction of the developmental time and the sensitivity of the frontal parts of the brain.”
 

Cognitive effects?

Although the researchers did not find any sex effects, Dr. Pfefferbaum stressed that this doesn’t mean they do not exist. “We just may not have the power to see them,” he said.

The study did not look specifically at binge drinkers, defined as consuming five drinks in 2 hours for men and four drinks in 2 hours for women. Dr. Pfefferbaum noted that it is difficult to get “good quantification” of binge drinking. “We don’t have a fine enough grain analysis to separate that out,” he said.

Asked whether the altered FA trajectory in heavy drinkers affects cognition, Dr. Pfefferbaum said “those studies are still in progress,” with results hopefully available within about a year.

Dr. Pfefferbaum said he and his colleagues are continuing to follow these adolescents and hope to see if the altered FA trajectory in heavy drinkers returns to normal, adding: “The real question now is: If they stop heavy drinking, will they get back on track?”

This study is believed to be the first to suggest in vivo differential vulnerability in WM microstructure with respect to age, the authors note.

In addition to asking teens about their alcohol use, the clinician’s role should be to “counsel and refer,” said Dr. Pfefferbaum. He also suggested accessing resources from the National Institute on Alcohol Abuse and Alcoholism.
 

Important data, but several limitations

In an interview, Oscar G. Bukstein, MD, MPH, medical director of outpatient psychiatry service at Boston Children’s Hospital, and professor of psychiatry at Harvard Medical School, also in Boston, said the findings provide further evidence that alcohol affects the maturing brain.

This study, and others that have examined cannabis use, “show that you have a dynamically growing brain with certain sections, particularly in this case the anterior and middle corpus callosum, that mature later [and] that are more likely to be affected by early alcohol use,” said Dr. Bukstein, who was not involved with the research.

He stressed the importance of determining the mechanism involved and noted some study limitations. For example, the DTI technology used may “already be out of date,” he said.

Using older technology may have prevented finding an impact of heavy drinking on parts of the brain other than the anterior and middle corpus callosum, Dr. Bukstein noted.

Newer technology might provide “a finer-grain nonlinear voxel-wise analysis,” although using more updated scanning techniques may not have detected additional differences in study groups, he added.

Dr. Bukstein also noted that there were limitations: The study did not have “gradations,” but only looked at heavy drinking and no to low drinking. “You’d like to find out about kids who are somewhere in the middle.” It also didn’t determine a “cutoff” where deleterious effects of alcohol on the brain begin, Dr. Bukstein added.

Additionally, the study didn’t look at brain development outcomes in children with conditions such as depression and ADHD that are known to lead to substance use – something a larger study may have been able to do, he said.

Dr. Bukstein noted that a newer and much larger study, the Adolescent Brain Cognitive Development study, has begun assessing kids for risk factors such as substance use, starting at age 10 years.

The study was funded by grants from NIAAA and by the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and the Stanford Institute for Human-Centered Artificial Intelligence–AWS Cloud Credits for Research. Dr. Pfefferbaum reported receiving an NIAAA grant during the conduct of the study. Dr. Bukstein disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the midst of an opioid overdose public health crisis, the US Department of Health and Human Services developed a 5-point strategy to combat this problem. One aspect of this strategy is improved pain management.¹ There is high demand for pain management services with a limited number of health care professionals appropriately trained to deliver care.² Pharmacists are integral members of the interdisciplinary pain team and meet this demand.

Background

For almost 50 years, pharmacists at the US Department of Veterans Affairs (VA) have been functioning as advanced practice providers (APP).³ Clinical pharmacy specialists (CPS) provide comprehensive medication management (CMM) and have a scope of practice (SOP). The SOP serves as the collaborating agreement and outlines the clinical duties permitted in delivering patient care. In addition, the SOP may indicate specific practice areas and are standardized across VA (Table 1).^4,5 Pharmacists apply for a SOP and must prove their competency in the practice area and provide documentation of their education, training, experience, knowledge, and skills.^5,6 Residency and/or board certification are not required though helpful. A pharmacist’s SOP is reviewed and approved by the facility executive committee.⁵ Pharmacists with a SOP undergo professional practice evaluation twice a year. Prescribing controlled substances is permissible in the SOP if approved by the facility and allowed by the state of licensure. According to the US Drug Enforcement Agency (DEA) as of February 10, 2020, 8 states (California, Washington, Idaho, Massachusetts, Montana, New Mexico, North Carolina, and Ohio) allow pharmacists to prescribe controlled substances.⁷

The VA developed the Pharmacists Achieve Results with Medications Documentation (PhARMD) tool that allows clinical pharmacists to document specific interventions made during clinical care and is included in their progress note. Data from fiscal year 2017 demonstrates that 136,041 pain management interventions were made by pharmacists across VA. The majority of these interventions were implemented by a CPS working autonomously as an APP.⁸

Several articles discuss the pharmacists role in the opioid crisis, although no outcomes data were provided. Chisholm-Burns and colleagues listed multiple potential ways that pharmacists can intervene, including managing pain in primary care clinic settings by using collaborative drug therapy agreements (CDTAs), using opioid exit plans and discharge planning in collaboration with other health care providers (HCPs), or making recommendations to the prescribers before writing prescriptions.⁹ Compton and colleagues similarly reviewed pharmacist roles in the opioid crisis. However, their focus was on dispensing pharmacists that provided education to patients about storage and disposal of opioids, identified opioid misuse, provided opioid overdose education and naloxone, and checked prescription drug monitoring programs (PDMPs).¹⁰ Missing from these articles was the role of the clinical pharmacist working as an APP delivering direct patient care and prescribing controlled substances.

Hammer and colleagues discussed the role of an oncology CPS with controlled substance prescriptive authority in pain management at an outpatient cancer center in Washington state.¹¹ Under a CDTA, pharmacists could prescribe medications, including controlled substances if they obtain DEA registration. The pharmacist completed a comprehensive in-person assessment. The attending physician conducted a physical examination. Then the pharmacist presented the patient and proposed regimen to the interprofessional team to determine a final plan. Ultimately, the pharmacist wrote any controlled substance prescriptions. The patient followed up every 1 to 4 weeks by telephone with a nurse, and in-person assessments occurred at least every 6 months. No outcomes data were provided.¹¹

Dole and colleagues reviewed the role of a pharmacist who had controlled substance prescriptive authority in a pain management clinic. The pharmacist provider saw up to 18 patients a day and then managed refill requests for 3 hours a day. The main outcome was change in visual analog scale (VAS) pain scores. Findings showed that reductions in VAS pain scores were statistically significant (P < .01). The pharmacist processed about 150 refills with an unclear number of controlled substances requests a day based on a medication-refill protocol. This was felt to improve access to physicians for acute needs, improve consistency in refills, and capture patients in need of follow-up. Additionally, the clinic saved $455,238 after 1 year.¹²

Study Aims

A review of the literature indicated sparse data on the impact of a pharmacist on opioid tapering, opioid dose, and opioid risk mitigation when the pharmacist is prescribing controlled substances. The purpose of this retrospective review was to characterize the controlled substance prescribing practices by the pharmacy pain clinic. The aim was to examine the pharmacist impact on morphine milligram equivalent (MME) and compliance with opioid risk mitigation strategies.

Methods

This project was a retrospective, single-center, chart review. The project was reviewed and approved by the University of Missouri-Columbia Institutional Review Board used by the Harry S. Truman Memorial Veterans’ Hospital (HSTMVH) as a quality improvement project. The author applied for controlled substance registration through the DEA and was issued registration April 30, 2018. The State of Ohio Board of Pharmacy was contacted as required by Ohio Administrative Code. The author's updated SOP to allow controlled substance prescribing was approved July 23, 2018. The CPS functions as an APP within an interdisciplinary pain management team that includes physicians, occupational and physical therapists, complementary and integrative health, and a psychologist. The reason for Pharmacy Pain Consult is required and it is primarily submitted through the electronic health record. The consult is reviewed for appropriateness and once approved is scheduled by support staff. Once the patient is stabilized, the patient is discharged back to their primary care provider (PCP) or referring provider for continued care. Patients were considered stabilized when their patient-specific goals were met, which varied from use of the lowest effective opioid dose to taper to discontinuation of opioids with no further medication changes needed. The taper strategy for each patient was individualized. Patients were generally tapered on their existing opioid medication unless they were new to the VA and on nonformulary medications or experiencing a significant adverse reaction. Numerous references are available through VA to assist with opioid tapering.^13,14 The CPS is able to refer patients to other services, including behavioral health for substance use disorder treatment and medication-assisted treatment if concerns were identified.

Initial data were collected from the Veterans Integrated Service Network (VISN) 15 Corporate Data Warehouse by the VISN pharmacy analytics program manager. The original report included patients prescribed a Schedule II to V controlled substance by the author from July 1, 2018 to January 31, 2020. Chart review was conducted on each patient to obtain additional data. At the time of consult and discharge the following data were collected: opioid medication; MME; use of opioid risk mitigation strategies, such as urine drug screens (UDS), informed consent, opioid overdose education and naloxone distribution program (OEND), risk assessment via stratification tool for opioid risk mitigation (STORM), PDMP checks; and nonopioid medication number and classes.

Patients were included in the review if they were prescribed an opioid Schedule II or III controlled substance between July 1, 2018 and January 31, 2020. Patient were excluded if they were prescribed an opioid Schedule II or III controlled substance primarily as coverage for another prescriber. Patients prescribed only pregabalin, tramadol, or a benzodiazepine also were excluded.

The primary endpoint was change in MME from baseline to discharge from clinic. Secondary endpoints included change in opioid risk mitigation strategies and change in opioid medications prescribed from baseline to discharge.

Descriptive statistics were used to analyze parts of the data. A 2-sided t test was used to compare baseline and discharge MME. The Fisher exact test was used to compare nominal data of opioid risk mitigation strategies.

Calculation of MME was performed using the conversion factors provided by the Centers Disease Control and Prevention (CDC) for opioid guideline.¹⁵ For buprenorphine, tapentadol, and levorphanol conversion ratios were obtained from other sources. The conversion ratios used, included 75:1 for oral morphine to transdermal buprenorphine, 1:3.3 for oral morphine to oral tapentadol, and 1:7.5 for oral levorphanol to oral morphine.^16,17 The Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) was used to write the manuscript.¹⁸

Results

Seventy-five patients were included in this review. The average age of patients was 66 years; and 12% were female (n = 9) (Table 2). The largest number of consults came from PCPs (44%, n = 33) and the pain clinic (43%, n = 32). Nearly half (48%) of the consultations were for opioid tapering (n = 36), followed by 37% for opioid optimization or monitoring (n = 28), and 19% for nonopioid optimization (n = 14). The most common primary diagnoses at consultation were for chronic low back pain (56%), chronic neck pain (20%), and osteoarthritis (16%).

The average MME at time of consult was 93 MME compared with 31 MME at discharge which was statisticially significant (P < .01) (Figure 1). The mean percent change in MME was 46%, including methadone and 42% excluding methadone. There was a 26% change in UDS, 28% change in informed consent, 85% change in PDMP, 194% change in naloxone, and 357% change in STORM reviews from baseline to discharge with all demonstrating statistical significance (P < .01) (Figure 2). At discharge, the most common opioid prescribed was morphine SA (short acting) (n = 10, 13%, 44 average MME) and oxycodone/acetaminophen (n = 10, 13%, 28 average MME) (Table 3).

The average number of days from consult to initial visit was 23 days (Table 4). Face-to-face was the primary means of initial visit with 92% (n = 69) of visits, but phone was the primary mode of follow-up with 73% of visits (n = 55). The average number of follow-up visits was 7, representing 176 average days of time in the Pharmacy Pain Clinic. Consultation to the behavioral health performance program was the most common referral (n = 13, 17%).

Discussion

There was a statistically significant decrease of the mean MME between the time of consult and the time of discharge. There also were statistically significant changes in use of opioid risk mitigation strategies. Since methadone has a high MME, the mean reduction of MME was calculated with methadone (46%) and without methadone (42%). These data are consistent with other published studies examining opioid tapers in the VA population. Harden and colleagues calculated a 46% mean reduction in MME over 12 months for 72 veterans from opioid tapers implemented by PCPs, pain service, or pharmacist-run clinics.¹⁹

There is controversy about equianalgesic doses and no established universal equianalgesic conversion calculator or dose. Numerous equianalgesic opioid dose calculators are available, but for this analysis the CDC MME conversion factors were used (available at: https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf). Previous literature compared existing calculators and found significant variances in calculated doses for methadone and fentanyl conversions.²⁰ Additionally, there have been concerns expressed with the safety of the CDC opioid calculator specifically surrounding the conversions for methadone and tapentadol.²¹ In the end, I chose the CDC calculator because it is established, readily available, and consistent.

Pharmacists in pain management can address access issues.^2,3,11,12 The average length of time from consult to initial visit was 23 days. Often patients may have seen a HCP who implemented a change at the time of consult and wanted the patient to be seen 1 month later. Many patients at the HSTMVH live far from the facility, making in-person visits difficult. A majority of the follow-up visits were conducted by telephone. Patients were offered all modalities available for follow-up, including telephone, in-person, or telemedicine, but patients most often picked telephone. Patients averaged 7 follow-up visits before discharge. This number of visits would have taken time from other health care team members who could have been addressing other veterans. Patients were seen in clinic for 176 days on average, which supports and follows recommendations for a slow, incremental taper.

The opioid medications prescribed changed over time in the clinic. Methadone prescriptions dropped from 20 to 6 at consult to discharge, and fentanyl prescriptions fell from 7 to 2, respectively. The CDC guideline suggests use of long-acting products with more predictable pharmacokinetics (eg, morphine SA or oxycodone SA) rather than fentanyl or methadone.¹⁵ Notably, the use of buprenorphine products with FDA approval for pain indications increased from consult to discharge. Many of the patients in this study had pulmonary comorbidities, placing them at higher risk for adverse outcomes. Buprenorphine is a partial μ-opioid receptor agonist with a ceiling on respiratory depression so is potentially less risky in those with pulmonary comorbidities.

The biggest changes in opioid risk mitigation occurred in PDMP, OEND program, and STORM reviews. An 85% increase in PDMP reviews occurred with referral to the clinic. Missouri is the only state without a state-run PDMP. However, the St. Louis County PDMP was developed based on city or county participation and encompasses 85% of the population of Missouri and 94% of HCPs in Missouri as of August 29, 2019.²² Because there is no state-level PDMP, a review of the St. Louis County PDMP was not required during the review period. Nevertheless, the Pharmacy Pain Clinic uses the St. Louis County PDMP at the initial visit and regularly during care. VA policy requires a specific note title be used to document each check of the PDMP.²³

There was a 194% increase in patients receiving naloxone with consultation to the Pharmacy Pain Clinic. Due to low coprescribing of naloxone for patients prescribed chronic opioid therapy, The author led an interdisciplinary team analysis of health care failure mode effects during the study period. This led to a process change with coprescribing of naloxone at refill in the primary care clinic.

The Comprehensive Addiction and Recovery Act of 2016 mandated that the VA review STORM on new start of opioids or patient identified as “very high-opioid prescription risk” category by an interdisciplinary opioid risk review team.²⁴ Thus many of the patients referred to clinic didn’t require STORM reviews since they were not new opioid starts or identified as high risk. However, in the standard review of all new patients to the Pharmacy Pain Clinic, a STORM review is conducted and documented to assess the patient’s level of risk.

Only 5 patients were started on opioid medications during the study period. This is consistent with both CDC and the joint VA/US Department of Defense opioid prescribing guidelines that recommend against initiation of opioids for chronic nonmalignant pain.^13,15 Two of the patients were prescribed tramadol for ineffective pain control at time of consult. Furthermore, 4 of the 5 patients were started on a short-acting opioid, which was supported by guidelines.^13,15 One patient was initiated on buprenorphine patches due to comorbid chronic kidney disease. The VA does not limit the quantity of new opioid prescriptions, although some states and private insurance plans are implementing limitations. Guidelines also recommend against exceeding 90 MME due to risk. The average MME in this project at discharge was 25 MME. Use of opioid risk mitigation for the new opioid starts was reasonable. The reason for the missing PDMP report is unknown based on chart review and atypical according to clinic practice.

Recently, efforts to expand pharmacist training and positions in pain management at VA facilities have been undertaken. In 2016, there were just 11 American Society of Health-System Pharmacists-accredited pharmacy postgraduate year 2 pain and palliative care residency programs, which has expanded to 26 sites in 2020.^2,3,25 In addition, the Clinical Pharmacy Practice Office and the VA Office of Rural Health have helped to hire 33 new pain management pharmacists.³

The role of pharmacists in prescribing controlled substances is limited mainly due to the small number of states that extend this authority.⁷ At the VA, a pharmacist can practice using any state of licensure. Therefore, a pharmacist working at a VA in a state that does not authorize controlled substance prescribing could obtain a license in a state that does permit it. However, the main barrier to obtaining other state licensures is the cost. At the time the author obtained controlled substance prescriptive authority, little direction was available on the process for advanced practice pharmacists at the VA. Since then, guidance has been developed to ease this process. Educational endeavors at VA have been implemented with the intent to increase the number of pharmacists with controlled substance prescriptive authority.

Barriers to pharmacists providing pain care extend beyond limited controlled substance prescriptive authority. Often pharmacists are still viewed in their traditional and operational role.^9,10 Other health care team members and patients may not be aware or familiar with the training, knowledge, and skills of pharmacist's and their suitability as an APP.^26,27 Most states permit pharmacists in establishing CDTA but not all. Additionally, some states recognize pharmacists as HCPs but many more do not. Furthermore, the Social Security Act does not include pharmacists as HCPs. This makes it challenging, though not impossible, for pharmacists to bill for their services.³

Strengths and Limitations

There were numerous strengths of the project. First, this addressed an unmet need in the literature with limited data discussing pharmacist prescribing controlled substances for pain management. There was 1 data reviewer who made the data collection process consistent. Since this retrospectively reviewed controlled substance prescribing in clinic, it captured real-world practice compared with that of experimental models. There were also several limitations in the project. The person collecting the data was also the person who conducted the clinic. The study was conducted retrospectively and based on documented information in the medical record. The population reviewed was primarily male and older, which fits the VA patient population but has less generalizability to other patient populations. This project was conducted at a single VA facility so may not be generalizable to other VA sites. It is unknown whether patients were again prescribed opioids if they left the VA for the community or another VA facility. The pain diagnoses or locations of pain were categorized to main groups and reliant on the referring provider. Another major weakness was the lack of comparison of pain scores or validated objective measure of function at baseline and at discharge. This consideration would be important for future work.

Conclusions

Pharmacists functioning as APP are key members of the pain management team. A review of a pharmacy-run pain clinic demonstrated statistically significant reduction in MME and improvement in opioid risk mitigation from consult to discharge. Patients enrolled in the pharmacy-managed clinic also had improvements in adherence to opioid risk mitigation strategies. Future attention should be focused on further expanding training and positions for pharmacists as APP in pain management.

Acknowledgments

The author thanks Chris Sedgwick for his assistance with data capture.

In the midst of an opioid overdose public health crisis, the US Department of Health and Human Services developed a 5-point strategy to combat this problem. One aspect of this strategy is improved pain management.¹ There is high demand for pain management services with a limited number of health care professionals appropriately trained to deliver care.² Pharmacists are integral members of the interdisciplinary pain team and meet this demand.

Background

For almost 50 years, pharmacists at the US Department of Veterans Affairs (VA) have been functioning as advanced practice providers (APP).³ Clinical pharmacy specialists (CPS) provide comprehensive medication management (CMM) and have a scope of practice (SOP). The SOP serves as the collaborating agreement and outlines the clinical duties permitted in delivering patient care. In addition, the SOP may indicate specific practice areas and are standardized across VA (Table 1).^4,5 Pharmacists apply for a SOP and must prove their competency in the practice area and provide documentation of their education, training, experience, knowledge, and skills.^5,6 Residency and/or board certification are not required though helpful. A pharmacist’s SOP is reviewed and approved by the facility executive committee.⁵ Pharmacists with a SOP undergo professional practice evaluation twice a year. Prescribing controlled substances is permissible in the SOP if approved by the facility and allowed by the state of licensure. According to the US Drug Enforcement Agency (DEA) as of February 10, 2020, 8 states (California, Washington, Idaho, Massachusetts, Montana, New Mexico, North Carolina, and Ohio) allow pharmacists to prescribe controlled substances.⁷

The VA developed the Pharmacists Achieve Results with Medications Documentation (PhARMD) tool that allows clinical pharmacists to document specific interventions made during clinical care and is included in their progress note. Data from fiscal year 2017 demonstrates that 136,041 pain management interventions were made by pharmacists across VA. The majority of these interventions were implemented by a CPS working autonomously as an APP.⁸

Several articles discuss the pharmacists role in the opioid crisis, although no outcomes data were provided. Chisholm-Burns and colleagues listed multiple potential ways that pharmacists can intervene, including managing pain in primary care clinic settings by using collaborative drug therapy agreements (CDTAs), using opioid exit plans and discharge planning in collaboration with other health care providers (HCPs), or making recommendations to the prescribers before writing prescriptions.⁹ Compton and colleagues similarly reviewed pharmacist roles in the opioid crisis. However, their focus was on dispensing pharmacists that provided education to patients about storage and disposal of opioids, identified opioid misuse, provided opioid overdose education and naloxone, and checked prescription drug monitoring programs (PDMPs).¹⁰ Missing from these articles was the role of the clinical pharmacist working as an APP delivering direct patient care and prescribing controlled substances.

Hammer and colleagues discussed the role of an oncology CPS with controlled substance prescriptive authority in pain management at an outpatient cancer center in Washington state.¹¹ Under a CDTA, pharmacists could prescribe medications, including controlled substances if they obtain DEA registration. The pharmacist completed a comprehensive in-person assessment. The attending physician conducted a physical examination. Then the pharmacist presented the patient and proposed regimen to the interprofessional team to determine a final plan. Ultimately, the pharmacist wrote any controlled substance prescriptions. The patient followed up every 1 to 4 weeks by telephone with a nurse, and in-person assessments occurred at least every 6 months. No outcomes data were provided.¹¹

Dole and colleagues reviewed the role of a pharmacist who had controlled substance prescriptive authority in a pain management clinic. The pharmacist provider saw up to 18 patients a day and then managed refill requests for 3 hours a day. The main outcome was change in visual analog scale (VAS) pain scores. Findings showed that reductions in VAS pain scores were statistically significant (P < .01). The pharmacist processed about 150 refills with an unclear number of controlled substances requests a day based on a medication-refill protocol. This was felt to improve access to physicians for acute needs, improve consistency in refills, and capture patients in need of follow-up. Additionally, the clinic saved $455,238 after 1 year.¹²

Study Aims

A review of the literature indicated sparse data on the impact of a pharmacist on opioid tapering, opioid dose, and opioid risk mitigation when the pharmacist is prescribing controlled substances. The purpose of this retrospective review was to characterize the controlled substance prescribing practices by the pharmacy pain clinic. The aim was to examine the pharmacist impact on morphine milligram equivalent (MME) and compliance with opioid risk mitigation strategies.

Methods

This project was a retrospective, single-center, chart review. The project was reviewed and approved by the University of Missouri-Columbia Institutional Review Board used by the Harry S. Truman Memorial Veterans’ Hospital (HSTMVH) as a quality improvement project. The author applied for controlled substance registration through the DEA and was issued registration April 30, 2018. The State of Ohio Board of Pharmacy was contacted as required by Ohio Administrative Code. The author's updated SOP to allow controlled substance prescribing was approved July 23, 2018. The CPS functions as an APP within an interdisciplinary pain management team that includes physicians, occupational and physical therapists, complementary and integrative health, and a psychologist. The reason for Pharmacy Pain Consult is required and it is primarily submitted through the electronic health record. The consult is reviewed for appropriateness and once approved is scheduled by support staff. Once the patient is stabilized, the patient is discharged back to their primary care provider (PCP) or referring provider for continued care. Patients were considered stabilized when their patient-specific goals were met, which varied from use of the lowest effective opioid dose to taper to discontinuation of opioids with no further medication changes needed. The taper strategy for each patient was individualized. Patients were generally tapered on their existing opioid medication unless they were new to the VA and on nonformulary medications or experiencing a significant adverse reaction. Numerous references are available through VA to assist with opioid tapering.^13,14 The CPS is able to refer patients to other services, including behavioral health for substance use disorder treatment and medication-assisted treatment if concerns were identified.

Initial data were collected from the Veterans Integrated Service Network (VISN) 15 Corporate Data Warehouse by the VISN pharmacy analytics program manager. The original report included patients prescribed a Schedule II to V controlled substance by the author from July 1, 2018 to January 31, 2020. Chart review was conducted on each patient to obtain additional data. At the time of consult and discharge the following data were collected: opioid medication; MME; use of opioid risk mitigation strategies, such as urine drug screens (UDS), informed consent, opioid overdose education and naloxone distribution program (OEND), risk assessment via stratification tool for opioid risk mitigation (STORM), PDMP checks; and nonopioid medication number and classes.

Patients were included in the review if they were prescribed an opioid Schedule II or III controlled substance between July 1, 2018 and January 31, 2020. Patient were excluded if they were prescribed an opioid Schedule II or III controlled substance primarily as coverage for another prescriber. Patients prescribed only pregabalin, tramadol, or a benzodiazepine also were excluded.

The primary endpoint was change in MME from baseline to discharge from clinic. Secondary endpoints included change in opioid risk mitigation strategies and change in opioid medications prescribed from baseline to discharge.

Descriptive statistics were used to analyze parts of the data. A 2-sided t test was used to compare baseline and discharge MME. The Fisher exact test was used to compare nominal data of opioid risk mitigation strategies.

Calculation of MME was performed using the conversion factors provided by the Centers Disease Control and Prevention (CDC) for opioid guideline.¹⁵ For buprenorphine, tapentadol, and levorphanol conversion ratios were obtained from other sources. The conversion ratios used, included 75:1 for oral morphine to transdermal buprenorphine, 1:3.3 for oral morphine to oral tapentadol, and 1:7.5 for oral levorphanol to oral morphine.^16,17 The Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) was used to write the manuscript.¹⁸

Results

Seventy-five patients were included in this review. The average age of patients was 66 years; and 12% were female (n = 9) (Table 2). The largest number of consults came from PCPs (44%, n = 33) and the pain clinic (43%, n = 32). Nearly half (48%) of the consultations were for opioid tapering (n = 36), followed by 37% for opioid optimization or monitoring (n = 28), and 19% for nonopioid optimization (n = 14). The most common primary diagnoses at consultation were for chronic low back pain (56%), chronic neck pain (20%), and osteoarthritis (16%).

The average MME at time of consult was 93 MME compared with 31 MME at discharge which was statisticially significant (P < .01) (Figure 1). The mean percent change in MME was 46%, including methadone and 42% excluding methadone. There was a 26% change in UDS, 28% change in informed consent, 85% change in PDMP, 194% change in naloxone, and 357% change in STORM reviews from baseline to discharge with all demonstrating statistical significance (P < .01) (Figure 2). At discharge, the most common opioid prescribed was morphine SA (short acting) (n = 10, 13%, 44 average MME) and oxycodone/acetaminophen (n = 10, 13%, 28 average MME) (Table 3).

The average number of days from consult to initial visit was 23 days (Table 4). Face-to-face was the primary means of initial visit with 92% (n = 69) of visits, but phone was the primary mode of follow-up with 73% of visits (n = 55). The average number of follow-up visits was 7, representing 176 average days of time in the Pharmacy Pain Clinic. Consultation to the behavioral health performance program was the most common referral (n = 13, 17%).

Discussion

There was a statistically significant decrease of the mean MME between the time of consult and the time of discharge. There also were statistically significant changes in use of opioid risk mitigation strategies. Since methadone has a high MME, the mean reduction of MME was calculated with methadone (46%) and without methadone (42%). These data are consistent with other published studies examining opioid tapers in the VA population. Harden and colleagues calculated a 46% mean reduction in MME over 12 months for 72 veterans from opioid tapers implemented by PCPs, pain service, or pharmacist-run clinics.¹⁹

There is controversy about equianalgesic doses and no established universal equianalgesic conversion calculator or dose. Numerous equianalgesic opioid dose calculators are available, but for this analysis the CDC MME conversion factors were used (available at: https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf). Previous literature compared existing calculators and found significant variances in calculated doses for methadone and fentanyl conversions.²⁰ Additionally, there have been concerns expressed with the safety of the CDC opioid calculator specifically surrounding the conversions for methadone and tapentadol.²¹ In the end, I chose the CDC calculator because it is established, readily available, and consistent.

Pharmacists in pain management can address access issues.^2,3,11,12 The average length of time from consult to initial visit was 23 days. Often patients may have seen a HCP who implemented a change at the time of consult and wanted the patient to be seen 1 month later. Many patients at the HSTMVH live far from the facility, making in-person visits difficult. A majority of the follow-up visits were conducted by telephone. Patients were offered all modalities available for follow-up, including telephone, in-person, or telemedicine, but patients most often picked telephone. Patients averaged 7 follow-up visits before discharge. This number of visits would have taken time from other health care team members who could have been addressing other veterans. Patients were seen in clinic for 176 days on average, which supports and follows recommendations for a slow, incremental taper.

The opioid medications prescribed changed over time in the clinic. Methadone prescriptions dropped from 20 to 6 at consult to discharge, and fentanyl prescriptions fell from 7 to 2, respectively. The CDC guideline suggests use of long-acting products with more predictable pharmacokinetics (eg, morphine SA or oxycodone SA) rather than fentanyl or methadone.¹⁵ Notably, the use of buprenorphine products with FDA approval for pain indications increased from consult to discharge. Many of the patients in this study had pulmonary comorbidities, placing them at higher risk for adverse outcomes. Buprenorphine is a partial μ-opioid receptor agonist with a ceiling on respiratory depression so is potentially less risky in those with pulmonary comorbidities.

The biggest changes in opioid risk mitigation occurred in PDMP, OEND program, and STORM reviews. An 85% increase in PDMP reviews occurred with referral to the clinic. Missouri is the only state without a state-run PDMP. However, the St. Louis County PDMP was developed based on city or county participation and encompasses 85% of the population of Missouri and 94% of HCPs in Missouri as of August 29, 2019.²² Because there is no state-level PDMP, a review of the St. Louis County PDMP was not required during the review period. Nevertheless, the Pharmacy Pain Clinic uses the St. Louis County PDMP at the initial visit and regularly during care. VA policy requires a specific note title be used to document each check of the PDMP.²³

There was a 194% increase in patients receiving naloxone with consultation to the Pharmacy Pain Clinic. Due to low coprescribing of naloxone for patients prescribed chronic opioid therapy, The author led an interdisciplinary team analysis of health care failure mode effects during the study period. This led to a process change with coprescribing of naloxone at refill in the primary care clinic.

The Comprehensive Addiction and Recovery Act of 2016 mandated that the VA review STORM on new start of opioids or patient identified as “very high-opioid prescription risk” category by an interdisciplinary opioid risk review team.²⁴ Thus many of the patients referred to clinic didn’t require STORM reviews since they were not new opioid starts or identified as high risk. However, in the standard review of all new patients to the Pharmacy Pain Clinic, a STORM review is conducted and documented to assess the patient’s level of risk.

Only 5 patients were started on opioid medications during the study period. This is consistent with both CDC and the joint VA/US Department of Defense opioid prescribing guidelines that recommend against initiation of opioids for chronic nonmalignant pain.^13,15 Two of the patients were prescribed tramadol for ineffective pain control at time of consult. Furthermore, 4 of the 5 patients were started on a short-acting opioid, which was supported by guidelines.^13,15 One patient was initiated on buprenorphine patches due to comorbid chronic kidney disease. The VA does not limit the quantity of new opioid prescriptions, although some states and private insurance plans are implementing limitations. Guidelines also recommend against exceeding 90 MME due to risk. The average MME in this project at discharge was 25 MME. Use of opioid risk mitigation for the new opioid starts was reasonable. The reason for the missing PDMP report is unknown based on chart review and atypical according to clinic practice.

Recently, efforts to expand pharmacist training and positions in pain management at VA facilities have been undertaken. In 2016, there were just 11 American Society of Health-System Pharmacists-accredited pharmacy postgraduate year 2 pain and palliative care residency programs, which has expanded to 26 sites in 2020.^2,3,25 In addition, the Clinical Pharmacy Practice Office and the VA Office of Rural Health have helped to hire 33 new pain management pharmacists.³

The role of pharmacists in prescribing controlled substances is limited mainly due to the small number of states that extend this authority.⁷ At the VA, a pharmacist can practice using any state of licensure. Therefore, a pharmacist working at a VA in a state that does not authorize controlled substance prescribing could obtain a license in a state that does permit it. However, the main barrier to obtaining other state licensures is the cost. At the time the author obtained controlled substance prescriptive authority, little direction was available on the process for advanced practice pharmacists at the VA. Since then, guidance has been developed to ease this process. Educational endeavors at VA have been implemented with the intent to increase the number of pharmacists with controlled substance prescriptive authority.

Barriers to pharmacists providing pain care extend beyond limited controlled substance prescriptive authority. Often pharmacists are still viewed in their traditional and operational role.^9,10 Other health care team members and patients may not be aware or familiar with the training, knowledge, and skills of pharmacist's and their suitability as an APP.^26,27 Most states permit pharmacists in establishing CDTA but not all. Additionally, some states recognize pharmacists as HCPs but many more do not. Furthermore, the Social Security Act does not include pharmacists as HCPs. This makes it challenging, though not impossible, for pharmacists to bill for their services.³

Strengths and Limitations

There were numerous strengths of the project. First, this addressed an unmet need in the literature with limited data discussing pharmacist prescribing controlled substances for pain management. There was 1 data reviewer who made the data collection process consistent. Since this retrospectively reviewed controlled substance prescribing in clinic, it captured real-world practice compared with that of experimental models. There were also several limitations in the project. The person collecting the data was also the person who conducted the clinic. The study was conducted retrospectively and based on documented information in the medical record. The population reviewed was primarily male and older, which fits the VA patient population but has less generalizability to other patient populations. This project was conducted at a single VA facility so may not be generalizable to other VA sites. It is unknown whether patients were again prescribed opioids if they left the VA for the community or another VA facility. The pain diagnoses or locations of pain were categorized to main groups and reliant on the referring provider. Another major weakness was the lack of comparison of pain scores or validated objective measure of function at baseline and at discharge. This consideration would be important for future work.

Conclusions

Pharmacists functioning as APP are key members of the pain management team. A review of a pharmacy-run pain clinic demonstrated statistically significant reduction in MME and improvement in opioid risk mitigation from consult to discharge. Patients enrolled in the pharmacy-managed clinic also had improvements in adherence to opioid risk mitigation strategies. Future attention should be focused on further expanding training and positions for pharmacists as APP in pain management.

Acknowledgments

The author thanks Chris Sedgwick for his assistance with data capture.

In the midst of an opioid overdose public health crisis, the US Department of Health and Human Services developed a 5-point strategy to combat this problem. One aspect of this strategy is improved pain management.¹ There is high demand for pain management services with a limited number of health care professionals appropriately trained to deliver care.² Pharmacists are integral members of the interdisciplinary pain team and meet this demand.

Background

For almost 50 years, pharmacists at the US Department of Veterans Affairs (VA) have been functioning as advanced practice providers (APP).³ Clinical pharmacy specialists (CPS) provide comprehensive medication management (CMM) and have a scope of practice (SOP). The SOP serves as the collaborating agreement and outlines the clinical duties permitted in delivering patient care. In addition, the SOP may indicate specific practice areas and are standardized across VA (Table 1).^4,5 Pharmacists apply for a SOP and must prove their competency in the practice area and provide documentation of their education, training, experience, knowledge, and skills.^5,6 Residency and/or board certification are not required though helpful. A pharmacist’s SOP is reviewed and approved by the facility executive committee.⁵ Pharmacists with a SOP undergo professional practice evaluation twice a year. Prescribing controlled substances is permissible in the SOP if approved by the facility and allowed by the state of licensure. According to the US Drug Enforcement Agency (DEA) as of February 10, 2020, 8 states (California, Washington, Idaho, Massachusetts, Montana, New Mexico, North Carolina, and Ohio) allow pharmacists to prescribe controlled substances.⁷

The VA developed the Pharmacists Achieve Results with Medications Documentation (PhARMD) tool that allows clinical pharmacists to document specific interventions made during clinical care and is included in their progress note. Data from fiscal year 2017 demonstrates that 136,041 pain management interventions were made by pharmacists across VA. The majority of these interventions were implemented by a CPS working autonomously as an APP.⁸

Several articles discuss the pharmacists role in the opioid crisis, although no outcomes data were provided. Chisholm-Burns and colleagues listed multiple potential ways that pharmacists can intervene, including managing pain in primary care clinic settings by using collaborative drug therapy agreements (CDTAs), using opioid exit plans and discharge planning in collaboration with other health care providers (HCPs), or making recommendations to the prescribers before writing prescriptions.⁹ Compton and colleagues similarly reviewed pharmacist roles in the opioid crisis. However, their focus was on dispensing pharmacists that provided education to patients about storage and disposal of opioids, identified opioid misuse, provided opioid overdose education and naloxone, and checked prescription drug monitoring programs (PDMPs).¹⁰ Missing from these articles was the role of the clinical pharmacist working as an APP delivering direct patient care and prescribing controlled substances.

Hammer and colleagues discussed the role of an oncology CPS with controlled substance prescriptive authority in pain management at an outpatient cancer center in Washington state.¹¹ Under a CDTA, pharmacists could prescribe medications, including controlled substances if they obtain DEA registration. The pharmacist completed a comprehensive in-person assessment. The attending physician conducted a physical examination. Then the pharmacist presented the patient and proposed regimen to the interprofessional team to determine a final plan. Ultimately, the pharmacist wrote any controlled substance prescriptions. The patient followed up every 1 to 4 weeks by telephone with a nurse, and in-person assessments occurred at least every 6 months. No outcomes data were provided.¹¹

Dole and colleagues reviewed the role of a pharmacist who had controlled substance prescriptive authority in a pain management clinic. The pharmacist provider saw up to 18 patients a day and then managed refill requests for 3 hours a day. The main outcome was change in visual analog scale (VAS) pain scores. Findings showed that reductions in VAS pain scores were statistically significant (P < .01). The pharmacist processed about 150 refills with an unclear number of controlled substances requests a day based on a medication-refill protocol. This was felt to improve access to physicians for acute needs, improve consistency in refills, and capture patients in need of follow-up. Additionally, the clinic saved $455,238 after 1 year.¹²

Study Aims

A review of the literature indicated sparse data on the impact of a pharmacist on opioid tapering, opioid dose, and opioid risk mitigation when the pharmacist is prescribing controlled substances. The purpose of this retrospective review was to characterize the controlled substance prescribing practices by the pharmacy pain clinic. The aim was to examine the pharmacist impact on morphine milligram equivalent (MME) and compliance with opioid risk mitigation strategies.

Methods

This project was a retrospective, single-center, chart review. The project was reviewed and approved by the University of Missouri-Columbia Institutional Review Board used by the Harry S. Truman Memorial Veterans’ Hospital (HSTMVH) as a quality improvement project. The author applied for controlled substance registration through the DEA and was issued registration April 30, 2018. The State of Ohio Board of Pharmacy was contacted as required by Ohio Administrative Code. The author's updated SOP to allow controlled substance prescribing was approved July 23, 2018. The CPS functions as an APP within an interdisciplinary pain management team that includes physicians, occupational and physical therapists, complementary and integrative health, and a psychologist. The reason for Pharmacy Pain Consult is required and it is primarily submitted through the electronic health record. The consult is reviewed for appropriateness and once approved is scheduled by support staff. Once the patient is stabilized, the patient is discharged back to their primary care provider (PCP) or referring provider for continued care. Patients were considered stabilized when their patient-specific goals were met, which varied from use of the lowest effective opioid dose to taper to discontinuation of opioids with no further medication changes needed. The taper strategy for each patient was individualized. Patients were generally tapered on their existing opioid medication unless they were new to the VA and on nonformulary medications or experiencing a significant adverse reaction. Numerous references are available through VA to assist with opioid tapering.^13,14 The CPS is able to refer patients to other services, including behavioral health for substance use disorder treatment and medication-assisted treatment if concerns were identified.

Initial data were collected from the Veterans Integrated Service Network (VISN) 15 Corporate Data Warehouse by the VISN pharmacy analytics program manager. The original report included patients prescribed a Schedule II to V controlled substance by the author from July 1, 2018 to January 31, 2020. Chart review was conducted on each patient to obtain additional data. At the time of consult and discharge the following data were collected: opioid medication; MME; use of opioid risk mitigation strategies, such as urine drug screens (UDS), informed consent, opioid overdose education and naloxone distribution program (OEND), risk assessment via stratification tool for opioid risk mitigation (STORM), PDMP checks; and nonopioid medication number and classes.

Patients were included in the review if they were prescribed an opioid Schedule II or III controlled substance between July 1, 2018 and January 31, 2020. Patient were excluded if they were prescribed an opioid Schedule II or III controlled substance primarily as coverage for another prescriber. Patients prescribed only pregabalin, tramadol, or a benzodiazepine also were excluded.

The primary endpoint was change in MME from baseline to discharge from clinic. Secondary endpoints included change in opioid risk mitigation strategies and change in opioid medications prescribed from baseline to discharge.

Descriptive statistics were used to analyze parts of the data. A 2-sided t test was used to compare baseline and discharge MME. The Fisher exact test was used to compare nominal data of opioid risk mitigation strategies.

Calculation of MME was performed using the conversion factors provided by the Centers Disease Control and Prevention (CDC) for opioid guideline.¹⁵ For buprenorphine, tapentadol, and levorphanol conversion ratios were obtained from other sources. The conversion ratios used, included 75:1 for oral morphine to transdermal buprenorphine, 1:3.3 for oral morphine to oral tapentadol, and 1:7.5 for oral levorphanol to oral morphine.^16,17 The Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) was used to write the manuscript.¹⁸

Results

Seventy-five patients were included in this review. The average age of patients was 66 years; and 12% were female (n = 9) (Table 2). The largest number of consults came from PCPs (44%, n = 33) and the pain clinic (43%, n = 32). Nearly half (48%) of the consultations were for opioid tapering (n = 36), followed by 37% for opioid optimization or monitoring (n = 28), and 19% for nonopioid optimization (n = 14). The most common primary diagnoses at consultation were for chronic low back pain (56%), chronic neck pain (20%), and osteoarthritis (16%).

The average MME at time of consult was 93 MME compared with 31 MME at discharge which was statisticially significant (P < .01) (Figure 1). The mean percent change in MME was 46%, including methadone and 42% excluding methadone. There was a 26% change in UDS, 28% change in informed consent, 85% change in PDMP, 194% change in naloxone, and 357% change in STORM reviews from baseline to discharge with all demonstrating statistical significance (P < .01) (Figure 2). At discharge, the most common opioid prescribed was morphine SA (short acting) (n = 10, 13%, 44 average MME) and oxycodone/acetaminophen (n = 10, 13%, 28 average MME) (Table 3).

The average number of days from consult to initial visit was 23 days (Table 4). Face-to-face was the primary means of initial visit with 92% (n = 69) of visits, but phone was the primary mode of follow-up with 73% of visits (n = 55). The average number of follow-up visits was 7, representing 176 average days of time in the Pharmacy Pain Clinic. Consultation to the behavioral health performance program was the most common referral (n = 13, 17%).

Discussion

There was a statistically significant decrease of the mean MME between the time of consult and the time of discharge. There also were statistically significant changes in use of opioid risk mitigation strategies. Since methadone has a high MME, the mean reduction of MME was calculated with methadone (46%) and without methadone (42%). These data are consistent with other published studies examining opioid tapers in the VA population. Harden and colleagues calculated a 46% mean reduction in MME over 12 months for 72 veterans from opioid tapers implemented by PCPs, pain service, or pharmacist-run clinics.¹⁹

There is controversy about equianalgesic doses and no established universal equianalgesic conversion calculator or dose. Numerous equianalgesic opioid dose calculators are available, but for this analysis the CDC MME conversion factors were used (available at: https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf). Previous literature compared existing calculators and found significant variances in calculated doses for methadone and fentanyl conversions.²⁰ Additionally, there have been concerns expressed with the safety of the CDC opioid calculator specifically surrounding the conversions for methadone and tapentadol.²¹ In the end, I chose the CDC calculator because it is established, readily available, and consistent.

Pharmacists in pain management can address access issues.^2,3,11,12 The average length of time from consult to initial visit was 23 days. Often patients may have seen a HCP who implemented a change at the time of consult and wanted the patient to be seen 1 month later. Many patients at the HSTMVH live far from the facility, making in-person visits difficult. A majority of the follow-up visits were conducted by telephone. Patients were offered all modalities available for follow-up, including telephone, in-person, or telemedicine, but patients most often picked telephone. Patients averaged 7 follow-up visits before discharge. This number of visits would have taken time from other health care team members who could have been addressing other veterans. Patients were seen in clinic for 176 days on average, which supports and follows recommendations for a slow, incremental taper.

The opioid medications prescribed changed over time in the clinic. Methadone prescriptions dropped from 20 to 6 at consult to discharge, and fentanyl prescriptions fell from 7 to 2, respectively. The CDC guideline suggests use of long-acting products with more predictable pharmacokinetics (eg, morphine SA or oxycodone SA) rather than fentanyl or methadone.¹⁵ Notably, the use of buprenorphine products with FDA approval for pain indications increased from consult to discharge. Many of the patients in this study had pulmonary comorbidities, placing them at higher risk for adverse outcomes. Buprenorphine is a partial μ-opioid receptor agonist with a ceiling on respiratory depression so is potentially less risky in those with pulmonary comorbidities.

The biggest changes in opioid risk mitigation occurred in PDMP, OEND program, and STORM reviews. An 85% increase in PDMP reviews occurred with referral to the clinic. Missouri is the only state without a state-run PDMP. However, the St. Louis County PDMP was developed based on city or county participation and encompasses 85% of the population of Missouri and 94% of HCPs in Missouri as of August 29, 2019.²² Because there is no state-level PDMP, a review of the St. Louis County PDMP was not required during the review period. Nevertheless, the Pharmacy Pain Clinic uses the St. Louis County PDMP at the initial visit and regularly during care. VA policy requires a specific note title be used to document each check of the PDMP.²³

There was a 194% increase in patients receiving naloxone with consultation to the Pharmacy Pain Clinic. Due to low coprescribing of naloxone for patients prescribed chronic opioid therapy, The author led an interdisciplinary team analysis of health care failure mode effects during the study period. This led to a process change with coprescribing of naloxone at refill in the primary care clinic.

The Comprehensive Addiction and Recovery Act of 2016 mandated that the VA review STORM on new start of opioids or patient identified as “very high-opioid prescription risk” category by an interdisciplinary opioid risk review team.²⁴ Thus many of the patients referred to clinic didn’t require STORM reviews since they were not new opioid starts or identified as high risk. However, in the standard review of all new patients to the Pharmacy Pain Clinic, a STORM review is conducted and documented to assess the patient’s level of risk.

Only 5 patients were started on opioid medications during the study period. This is consistent with both CDC and the joint VA/US Department of Defense opioid prescribing guidelines that recommend against initiation of opioids for chronic nonmalignant pain.^13,15 Two of the patients were prescribed tramadol for ineffective pain control at time of consult. Furthermore, 4 of the 5 patients were started on a short-acting opioid, which was supported by guidelines.^13,15 One patient was initiated on buprenorphine patches due to comorbid chronic kidney disease. The VA does not limit the quantity of new opioid prescriptions, although some states and private insurance plans are implementing limitations. Guidelines also recommend against exceeding 90 MME due to risk. The average MME in this project at discharge was 25 MME. Use of opioid risk mitigation for the new opioid starts was reasonable. The reason for the missing PDMP report is unknown based on chart review and atypical according to clinic practice.

Recently, efforts to expand pharmacist training and positions in pain management at VA facilities have been undertaken. In 2016, there were just 11 American Society of Health-System Pharmacists-accredited pharmacy postgraduate year 2 pain and palliative care residency programs, which has expanded to 26 sites in 2020.^2,3,25 In addition, the Clinical Pharmacy Practice Office and the VA Office of Rural Health have helped to hire 33 new pain management pharmacists.³

The role of pharmacists in prescribing controlled substances is limited mainly due to the small number of states that extend this authority.⁷ At the VA, a pharmacist can practice using any state of licensure. Therefore, a pharmacist working at a VA in a state that does not authorize controlled substance prescribing could obtain a license in a state that does permit it. However, the main barrier to obtaining other state licensures is the cost. At the time the author obtained controlled substance prescriptive authority, little direction was available on the process for advanced practice pharmacists at the VA. Since then, guidance has been developed to ease this process. Educational endeavors at VA have been implemented with the intent to increase the number of pharmacists with controlled substance prescriptive authority.

Barriers to pharmacists providing pain care extend beyond limited controlled substance prescriptive authority. Often pharmacists are still viewed in their traditional and operational role.^9,10 Other health care team members and patients may not be aware or familiar with the training, knowledge, and skills of pharmacist's and their suitability as an APP.^26,27 Most states permit pharmacists in establishing CDTA but not all. Additionally, some states recognize pharmacists as HCPs but many more do not. Furthermore, the Social Security Act does not include pharmacists as HCPs. This makes it challenging, though not impossible, for pharmacists to bill for their services.³

Strengths and Limitations

There were numerous strengths of the project. First, this addressed an unmet need in the literature with limited data discussing pharmacist prescribing controlled substances for pain management. There was 1 data reviewer who made the data collection process consistent. Since this retrospectively reviewed controlled substance prescribing in clinic, it captured real-world practice compared with that of experimental models. There were also several limitations in the project. The person collecting the data was also the person who conducted the clinic. The study was conducted retrospectively and based on documented information in the medical record. The population reviewed was primarily male and older, which fits the VA patient population but has less generalizability to other patient populations. This project was conducted at a single VA facility so may not be generalizable to other VA sites. It is unknown whether patients were again prescribed opioids if they left the VA for the community or another VA facility. The pain diagnoses or locations of pain were categorized to main groups and reliant on the referring provider. Another major weakness was the lack of comparison of pain scores or validated objective measure of function at baseline and at discharge. This consideration would be important for future work.

Conclusions

Pharmacists functioning as APP are key members of the pain management team. A review of a pharmacy-run pain clinic demonstrated statistically significant reduction in MME and improvement in opioid risk mitigation from consult to discharge. Patients enrolled in the pharmacy-managed clinic also had improvements in adherence to opioid risk mitigation strategies. Future attention should be focused on further expanding training and positions for pharmacists as APP in pain management.

Acknowledgments

The author thanks Chris Sedgwick for his assistance with data capture.

Editor's Note: Due to updated statistics from the CDC, the online version of this article has been modified from the version that appears in the printed edition of the January 2021 issue of Current Psychiatry.

Individuals with mental health and substance use disorders (SUDs) are particularly susceptible to negative effects of the coronavirus disease 2019 (COVID-19) pandemic. The collision of the COVID-19 pandemic and the drug overdose epidemic has highlighted the urgent need for physicians, policymakers, and health care professionals to optimize care for individuals with SUDs because they may be particularly vulnerable to the effects of the virus due to compromised respiratory and immune function, and poor social support.¹  In this commentary, we highlight the challenges of the drug overdose epidemic, and recommend strategies to mitigate the impact of the COVID-19 pandemic among patients with SUDs.  

A crisis exacerbated by COVID-19 

The current drug overdose epidemic has become an American public health nightmare. According to preliminary data released by the CDC on December 17, 2020, there were more than 81,000 drug overdose deaths in the United States in the 12 months ending May 2020.^2,3 This is the highest number of overdose deaths ever recorded in a 12-month period. The CDC also noted that while overdose deaths were already increasing in the months preceding the COVID-19 pandemic, the latest numbers suggest an acceleration of overdose deaths during the pandemic.

What is causing this significant loss of life? Prescription opioids and illegal opioids such as heroin and illicitly manufactured fentanyl are the main agents associated with overdose deaths. These opioids were responsible for 61% (28,647) of drug overdose deaths in the United States in 2014.⁴ In 2015, the opioid overdose death rate increased by 15.6%.⁵  

The increase in the number of opioid overdose deaths in part coincides with a sharp increase in the availability and use of heroin. Heroin overdose deaths have more than tripled since 2010, but heroin is not the only opiate involved. Fentanyl, a synthetic, short-acting opioid that is approved for managing pain in patients with advanced cancers, is 50 times more potent than heroin. The abuse of prescribed fentanyl has been accelerating over the past decade, as is the use of illicitly produced fentanyl. Evidence from US Drug Enforcement Administration (DEA) seizure records shows heroin is being adulterated with illicit fentanyl to enhance the potency of the heroin.^6,7 Mixing illicit fentanyl with heroin may be contributing to the recent increase in heroin overdose fatalities. According to the CDC, overdose deaths related to synthetic opioids increased 38.4% from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020.^2,3 Postmortem studies of individuals who died from a heroin overdose have frequently found the presence of fentanyl along with heroin.⁸ Overdose deaths involving heroin may be occurring because individuals may be unknowingly using heroin adulterated with fentanyl.⁹ In addition, carfentanil, a powerful new synthetic fentanyl, has been recently identified in heroin mixtures. Carfentanil is 10,000 times stronger than morphine. Even in miniscule amounts, carfentanil can suppress breathing to the degree that multiple doses of naloxone are needed to restore respirations.

Initial studies indicate that the COVID-19 pandemic has been exacerbating this situation. Wainwright et al¹⁰ conducted an analysis of urine drug test results of patients with SUDs from 4 months before and 4 months after COVID-19 was declared a national emergency on March 13, 2020. Compared with before COVID-19, the proportion of specimens testing positive since COVID-19 increased from 3.80% to 7.32% for fentanyl and from 1.29% to 2.09% for heroin.¹⁰  

A similar drug testing study found that during the pandemic, the proportion of positive results (positivity) increased by 35% for non-prescribed fentanyl and 44% for heroin.¹¹ Positivity for non-prescribed fentanyl increased significantly among patients who tested positive for other drugs, including by 89% for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < .1 for all).¹¹ 

In a review of electronic medical records, Ochalek et al¹² found that the number of nonfatal opioid overdoses in an emergency department in Virginia increased from 102 in March-June 2019 to 227 in March-June 2020. In an issue brief published on October 31, 2020, the American Medical Association reported increase in opioid and other drug-related overdoses in more than 40 states during the COVID-19 pandemic.¹³ 

Continue to: Strategies for intervention...

Strategies for intervention 

A multi-dimensional approach is needed to protect the public from this growing opioid overdose epidemic. To address this challenging task, we recommend several strategies: 

Enhance access to virtual treatment 
Even when in-person treatment cannot take place due to COVID-19-related restrictions, it is vital that services are accessible to patients with SUDs during this pandemic. Examples of virtual treatment include: 

• Telehealth for medication-assisted treatment (MAT) using buprenorphine (recently updated guidance from the US DEA and Substance Abuse and Mental Health Services Administration [SAMHSA] allows this method of prescribing) 
• Teletherapy to prevent relapse  
• Remote drug screens by sending saliva or urine kits to patients' homes, visiting patients to collect fluid samples, or asking patients to come to a "drive-through" facility to provide samples  
• Virtual (online) Alcoholics Anonymous, Narcotics Anonymous, SMART Recovery, and similar meetings to provide support in the absence of in-person meetings.  

The American Society of Addiction Medicine (ASAM) offers guidance to treatment programs to focus on infection control and mitigation. The Table¹⁴ summarizes the ASAM recommendations for office-based opioid treatment during COVID-19.

Continue to: Increase education on naloxone...  

Increase education on naloxone  
Naloxone is a safe and effective opioid antagonist used to treat opioid overdoses. Timely access to naloxone is of the essence when treating opioid-related overdoses. Many states have enacted laws allowing health care professionals, law enforcement officers, and patients and relatives to obtain naloxone without a physician's prescription. It appears this approach may be yielding results. For example, the North Carolina Harm Reduction Coalition distributed >101,000 free overdose rescue kits that included naloxone and recorded 13,392 confirmed cases of overdose rescue with naloxone from 2013 to 2019.¹⁶ 

Divert patients with SUDs from the criminal justice system to treatment 
We need to develop programs to divert patients with SUDs from the criminal justice system, which is focused on punishment, to interventions that focus on treatment. Data indicates high recidivism rates for incarcerated individuals with SUDs who do not have access to treatment after they are released. Recognizing this, communities are developing programs that divert low-level offenders from the criminal justice system into treatment. For instance, in Seattle, the Law Enforcement Assisted Diversion is a pilot program developed to divert low-level drug and prostitution offenders into community-based treatment and support services. This helps provide housing, health care, job training, treatment, and mental health support. Innovative programs are needed to provide SUD treatment in the rehabilitation programs of correctional facilities and ensure case managers and discharge planners can transition participants to community treatment programs upon their release. 

Develop early identification and prevention programs  
These programs should focus on individuals at high risk, such as patients with comorbid SUDs and psychiatric disorders, those with chronic pain, and at-risk children whose parents abuse opiates. Traditional addiction treatment programs typically do not address patients with complex conditions or special populations, such as adolescents or pregnant women with substance use issues. Evidence-based approaches such as Screening, Brief Intervention, and Referral to Treatment (SBIRT), Integrated Dual Diagnosis Treatment (IDDT), and prevention approaches that target students in middle schools and high schools need to be more widely available. 

Improve education on opioid prescribing   
Responsible opioid prescribing for clinicians should include education about the regular use of prescription drug monitoring programs, urine drug screening, avoiding co-prescription of opioids with sedative-hypnotic medications, and better linkage with addiction treatment. 

Treat comorbid psychiatric conditions 
It is critical to both identify and effectively treat underlying affective, anxiety, and psychotic disorders in patients with SUDs. Anxiety, depression, and emotional dysregulation often contribute to worsening substance abuse, abuse of prescription drugs, diversion of prescribed drugs, and an increased risk of overdoses and suicides. Effective treatment of comorbid psychiatric conditions also may reduce relapses.  

Increase research on causes and treatments 
Through research, we must expand our knowledge to better understand the factors that contribute to this epidemic and develop better treatments. These efforts may allow for the development of prevention mechanisms. For example, a recent study found that the continued use of opioid medications after an overdose was associated with a high risk of a repeated overdosecall out material?.¹⁷ At the end of a 2-year observation, 17% (confidence interval [CI]: 14% to 20%) of patients receiving a high daily dosage of a prescribed opioid had a repeat overdose compared with 15% (CI: 10% to 21%) of those receiving a moderate dosage, 9% (CI: 6% to 14%) of those receiving a low dosage, and 8% (CI: 6% to 11%) of those receiving no opioids.¹⁷ Of the patients who overdosed on prescribed opiates, 30% switched to a new prescriber after their overdose, many of whom may not have been aware of the previous overdose. From a public health perspective, it would make sense for prescribers to know of prior opioid and/or benzodiazepine overdoses. This could be reported by emergency department clinicians, law enforcement, and hospitals into a prescription drug monitoring program, which is readily available to prescribers in most states. 

Acknowledgment 
The authors thank Scott Proescholdbell, MPH, Injury and Violence Prevention Branch, Chronic Disease and Injury Section, Division of Public Health, North Carolina Department of Health and Human Services, for his assistance. 

Bottom Line

The collision of the coronavirus disease 2019 pandemic and the drug overdose epidemic has highlighted the urgent need for health care professionals to optimize care for individuals with substance use disorders. Suggested interventions include enhancing access to medication-assisted treatment and virtual treatment, improving education about naloxone and safe opioid prescribing practices, and diverting at-risk patients from the criminal justice system to interventions that focus on treatment.

Editor's Note: Due to updated statistics from the CDC, the online version of this article has been modified from the version that appears in the printed edition of the January 2021 issue of Current Psychiatry.

Individuals with mental health and substance use disorders (SUDs) are particularly susceptible to negative effects of the coronavirus disease 2019 (COVID-19) pandemic. The collision of the COVID-19 pandemic and the drug overdose epidemic has highlighted the urgent need for physicians, policymakers, and health care professionals to optimize care for individuals with SUDs because they may be particularly vulnerable to the effects of the virus due to compromised respiratory and immune function, and poor social support.¹  In this commentary, we highlight the challenges of the drug overdose epidemic, and recommend strategies to mitigate the impact of the COVID-19 pandemic among patients with SUDs.  

A crisis exacerbated by COVID-19 

The current drug overdose epidemic has become an American public health nightmare. According to preliminary data released by the CDC on December 17, 2020, there were more than 81,000 drug overdose deaths in the United States in the 12 months ending May 2020.^2,3 This is the highest number of overdose deaths ever recorded in a 12-month period. The CDC also noted that while overdose deaths were already increasing in the months preceding the COVID-19 pandemic, the latest numbers suggest an acceleration of overdose deaths during the pandemic.

What is causing this significant loss of life? Prescription opioids and illegal opioids such as heroin and illicitly manufactured fentanyl are the main agents associated with overdose deaths. These opioids were responsible for 61% (28,647) of drug overdose deaths in the United States in 2014.⁴ In 2015, the opioid overdose death rate increased by 15.6%.⁵  

The increase in the number of opioid overdose deaths in part coincides with a sharp increase in the availability and use of heroin. Heroin overdose deaths have more than tripled since 2010, but heroin is not the only opiate involved. Fentanyl, a synthetic, short-acting opioid that is approved for managing pain in patients with advanced cancers, is 50 times more potent than heroin. The abuse of prescribed fentanyl has been accelerating over the past decade, as is the use of illicitly produced fentanyl. Evidence from US Drug Enforcement Administration (DEA) seizure records shows heroin is being adulterated with illicit fentanyl to enhance the potency of the heroin.^6,7 Mixing illicit fentanyl with heroin may be contributing to the recent increase in heroin overdose fatalities. According to the CDC, overdose deaths related to synthetic opioids increased 38.4% from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020.^2,3 Postmortem studies of individuals who died from a heroin overdose have frequently found the presence of fentanyl along with heroin.⁸ Overdose deaths involving heroin may be occurring because individuals may be unknowingly using heroin adulterated with fentanyl.⁹ In addition, carfentanil, a powerful new synthetic fentanyl, has been recently identified in heroin mixtures. Carfentanil is 10,000 times stronger than morphine. Even in miniscule amounts, carfentanil can suppress breathing to the degree that multiple doses of naloxone are needed to restore respirations.

Initial studies indicate that the COVID-19 pandemic has been exacerbating this situation. Wainwright et al¹⁰ conducted an analysis of urine drug test results of patients with SUDs from 4 months before and 4 months after COVID-19 was declared a national emergency on March 13, 2020. Compared with before COVID-19, the proportion of specimens testing positive since COVID-19 increased from 3.80% to 7.32% for fentanyl and from 1.29% to 2.09% for heroin.¹⁰  

A similar drug testing study found that during the pandemic, the proportion of positive results (positivity) increased by 35% for non-prescribed fentanyl and 44% for heroin.¹¹ Positivity for non-prescribed fentanyl increased significantly among patients who tested positive for other drugs, including by 89% for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < .1 for all).¹¹ 

In a review of electronic medical records, Ochalek et al¹² found that the number of nonfatal opioid overdoses in an emergency department in Virginia increased from 102 in March-June 2019 to 227 in March-June 2020. In an issue brief published on October 31, 2020, the American Medical Association reported increase in opioid and other drug-related overdoses in more than 40 states during the COVID-19 pandemic.¹³ 

Continue to: Strategies for intervention...

Strategies for intervention 

A multi-dimensional approach is needed to protect the public from this growing opioid overdose epidemic. To address this challenging task, we recommend several strategies: 

Enhance access to virtual treatment 
Even when in-person treatment cannot take place due to COVID-19-related restrictions, it is vital that services are accessible to patients with SUDs during this pandemic. Examples of virtual treatment include: 

• Telehealth for medication-assisted treatment (MAT) using buprenorphine (recently updated guidance from the US DEA and Substance Abuse and Mental Health Services Administration [SAMHSA] allows this method of prescribing) 
• Teletherapy to prevent relapse  
• Remote drug screens by sending saliva or urine kits to patients' homes, visiting patients to collect fluid samples, or asking patients to come to a "drive-through" facility to provide samples  
• Virtual (online) Alcoholics Anonymous, Narcotics Anonymous, SMART Recovery, and similar meetings to provide support in the absence of in-person meetings.  

The American Society of Addiction Medicine (ASAM) offers guidance to treatment programs to focus on infection control and mitigation. The Table¹⁴ summarizes the ASAM recommendations for office-based opioid treatment during COVID-19.

Continue to: Increase education on naloxone...  

Increase education on naloxone  
Naloxone is a safe and effective opioid antagonist used to treat opioid overdoses. Timely access to naloxone is of the essence when treating opioid-related overdoses. Many states have enacted laws allowing health care professionals, law enforcement officers, and patients and relatives to obtain naloxone without a physician's prescription. It appears this approach may be yielding results. For example, the North Carolina Harm Reduction Coalition distributed >101,000 free overdose rescue kits that included naloxone and recorded 13,392 confirmed cases of overdose rescue with naloxone from 2013 to 2019.¹⁶ 

Divert patients with SUDs from the criminal justice system to treatment 
We need to develop programs to divert patients with SUDs from the criminal justice system, which is focused on punishment, to interventions that focus on treatment. Data indicates high recidivism rates for incarcerated individuals with SUDs who do not have access to treatment after they are released. Recognizing this, communities are developing programs that divert low-level offenders from the criminal justice system into treatment. For instance, in Seattle, the Law Enforcement Assisted Diversion is a pilot program developed to divert low-level drug and prostitution offenders into community-based treatment and support services. This helps provide housing, health care, job training, treatment, and mental health support. Innovative programs are needed to provide SUD treatment in the rehabilitation programs of correctional facilities and ensure case managers and discharge planners can transition participants to community treatment programs upon their release. 

Develop early identification and prevention programs  
These programs should focus on individuals at high risk, such as patients with comorbid SUDs and psychiatric disorders, those with chronic pain, and at-risk children whose parents abuse opiates. Traditional addiction treatment programs typically do not address patients with complex conditions or special populations, such as adolescents or pregnant women with substance use issues. Evidence-based approaches such as Screening, Brief Intervention, and Referral to Treatment (SBIRT), Integrated Dual Diagnosis Treatment (IDDT), and prevention approaches that target students in middle schools and high schools need to be more widely available. 

Improve education on opioid prescribing   
Responsible opioid prescribing for clinicians should include education about the regular use of prescription drug monitoring programs, urine drug screening, avoiding co-prescription of opioids with sedative-hypnotic medications, and better linkage with addiction treatment. 

Treat comorbid psychiatric conditions 
It is critical to both identify and effectively treat underlying affective, anxiety, and psychotic disorders in patients with SUDs. Anxiety, depression, and emotional dysregulation often contribute to worsening substance abuse, abuse of prescription drugs, diversion of prescribed drugs, and an increased risk of overdoses and suicides. Effective treatment of comorbid psychiatric conditions also may reduce relapses.  

Increase research on causes and treatments 
Through research, we must expand our knowledge to better understand the factors that contribute to this epidemic and develop better treatments. These efforts may allow for the development of prevention mechanisms. For example, a recent study found that the continued use of opioid medications after an overdose was associated with a high risk of a repeated overdosecall out material?.¹⁷ At the end of a 2-year observation, 17% (confidence interval [CI]: 14% to 20%) of patients receiving a high daily dosage of a prescribed opioid had a repeat overdose compared with 15% (CI: 10% to 21%) of those receiving a moderate dosage, 9% (CI: 6% to 14%) of those receiving a low dosage, and 8% (CI: 6% to 11%) of those receiving no opioids.¹⁷ Of the patients who overdosed on prescribed opiates, 30% switched to a new prescriber after their overdose, many of whom may not have been aware of the previous overdose. From a public health perspective, it would make sense for prescribers to know of prior opioid and/or benzodiazepine overdoses. This could be reported by emergency department clinicians, law enforcement, and hospitals into a prescription drug monitoring program, which is readily available to prescribers in most states. 

Acknowledgment 
The authors thank Scott Proescholdbell, MPH, Injury and Violence Prevention Branch, Chronic Disease and Injury Section, Division of Public Health, North Carolina Department of Health and Human Services, for his assistance. 

Bottom Line

The collision of the coronavirus disease 2019 pandemic and the drug overdose epidemic has highlighted the urgent need for health care professionals to optimize care for individuals with substance use disorders. Suggested interventions include enhancing access to medication-assisted treatment and virtual treatment, improving education about naloxone and safe opioid prescribing practices, and diverting at-risk patients from the criminal justice system to interventions that focus on treatment.

Editor's Note: Due to updated statistics from the CDC, the online version of this article has been modified from the version that appears in the printed edition of the January 2021 issue of Current Psychiatry.

Individuals with mental health and substance use disorders (SUDs) are particularly susceptible to negative effects of the coronavirus disease 2019 (COVID-19) pandemic. The collision of the COVID-19 pandemic and the drug overdose epidemic has highlighted the urgent need for physicians, policymakers, and health care professionals to optimize care for individuals with SUDs because they may be particularly vulnerable to the effects of the virus due to compromised respiratory and immune function, and poor social support.¹  In this commentary, we highlight the challenges of the drug overdose epidemic, and recommend strategies to mitigate the impact of the COVID-19 pandemic among patients with SUDs.  

A crisis exacerbated by COVID-19 

The current drug overdose epidemic has become an American public health nightmare. According to preliminary data released by the CDC on December 17, 2020, there were more than 81,000 drug overdose deaths in the United States in the 12 months ending May 2020.^2,3 This is the highest number of overdose deaths ever recorded in a 12-month period. The CDC also noted that while overdose deaths were already increasing in the months preceding the COVID-19 pandemic, the latest numbers suggest an acceleration of overdose deaths during the pandemic.

What is causing this significant loss of life? Prescription opioids and illegal opioids such as heroin and illicitly manufactured fentanyl are the main agents associated with overdose deaths. These opioids were responsible for 61% (28,647) of drug overdose deaths in the United States in 2014.⁴ In 2015, the opioid overdose death rate increased by 15.6%.⁵  

The increase in the number of opioid overdose deaths in part coincides with a sharp increase in the availability and use of heroin. Heroin overdose deaths have more than tripled since 2010, but heroin is not the only opiate involved. Fentanyl, a synthetic, short-acting opioid that is approved for managing pain in patients with advanced cancers, is 50 times more potent than heroin. The abuse of prescribed fentanyl has been accelerating over the past decade, as is the use of illicitly produced fentanyl. Evidence from US Drug Enforcement Administration (DEA) seizure records shows heroin is being adulterated with illicit fentanyl to enhance the potency of the heroin.^6,7 Mixing illicit fentanyl with heroin may be contributing to the recent increase in heroin overdose fatalities. According to the CDC, overdose deaths related to synthetic opioids increased 38.4% from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020.^2,3 Postmortem studies of individuals who died from a heroin overdose have frequently found the presence of fentanyl along with heroin.⁸ Overdose deaths involving heroin may be occurring because individuals may be unknowingly using heroin adulterated with fentanyl.⁹ In addition, carfentanil, a powerful new synthetic fentanyl, has been recently identified in heroin mixtures. Carfentanil is 10,000 times stronger than morphine. Even in miniscule amounts, carfentanil can suppress breathing to the degree that multiple doses of naloxone are needed to restore respirations.

Initial studies indicate that the COVID-19 pandemic has been exacerbating this situation. Wainwright et al¹⁰ conducted an analysis of urine drug test results of patients with SUDs from 4 months before and 4 months after COVID-19 was declared a national emergency on March 13, 2020. Compared with before COVID-19, the proportion of specimens testing positive since COVID-19 increased from 3.80% to 7.32% for fentanyl and from 1.29% to 2.09% for heroin.¹⁰  

A similar drug testing study found that during the pandemic, the proportion of positive results (positivity) increased by 35% for non-prescribed fentanyl and 44% for heroin.¹¹ Positivity for non-prescribed fentanyl increased significantly among patients who tested positive for other drugs, including by 89% for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < .1 for all).¹¹ 

In a review of electronic medical records, Ochalek et al¹² found that the number of nonfatal opioid overdoses in an emergency department in Virginia increased from 102 in March-June 2019 to 227 in March-June 2020. In an issue brief published on October 31, 2020, the American Medical Association reported increase in opioid and other drug-related overdoses in more than 40 states during the COVID-19 pandemic.¹³ 

Continue to: Strategies for intervention...

Strategies for intervention 

A multi-dimensional approach is needed to protect the public from this growing opioid overdose epidemic. To address this challenging task, we recommend several strategies: 

Enhance access to virtual treatment 
Even when in-person treatment cannot take place due to COVID-19-related restrictions, it is vital that services are accessible to patients with SUDs during this pandemic. Examples of virtual treatment include: 

• Telehealth for medication-assisted treatment (MAT) using buprenorphine (recently updated guidance from the US DEA and Substance Abuse and Mental Health Services Administration [SAMHSA] allows this method of prescribing) 
• Teletherapy to prevent relapse  
• Remote drug screens by sending saliva or urine kits to patients' homes, visiting patients to collect fluid samples, or asking patients to come to a "drive-through" facility to provide samples  
• Virtual (online) Alcoholics Anonymous, Narcotics Anonymous, SMART Recovery, and similar meetings to provide support in the absence of in-person meetings.  

The American Society of Addiction Medicine (ASAM) offers guidance to treatment programs to focus on infection control and mitigation. The Table¹⁴ summarizes the ASAM recommendations for office-based opioid treatment during COVID-19.

Continue to: Increase education on naloxone...  

Increase education on naloxone  
Naloxone is a safe and effective opioid antagonist used to treat opioid overdoses. Timely access to naloxone is of the essence when treating opioid-related overdoses. Many states have enacted laws allowing health care professionals, law enforcement officers, and patients and relatives to obtain naloxone without a physician's prescription. It appears this approach may be yielding results. For example, the North Carolina Harm Reduction Coalition distributed >101,000 free overdose rescue kits that included naloxone and recorded 13,392 confirmed cases of overdose rescue with naloxone from 2013 to 2019.¹⁶ 

Divert patients with SUDs from the criminal justice system to treatment 
We need to develop programs to divert patients with SUDs from the criminal justice system, which is focused on punishment, to interventions that focus on treatment. Data indicates high recidivism rates for incarcerated individuals with SUDs who do not have access to treatment after they are released. Recognizing this, communities are developing programs that divert low-level offenders from the criminal justice system into treatment. For instance, in Seattle, the Law Enforcement Assisted Diversion is a pilot program developed to divert low-level drug and prostitution offenders into community-based treatment and support services. This helps provide housing, health care, job training, treatment, and mental health support. Innovative programs are needed to provide SUD treatment in the rehabilitation programs of correctional facilities and ensure case managers and discharge planners can transition participants to community treatment programs upon their release. 

Develop early identification and prevention programs  
These programs should focus on individuals at high risk, such as patients with comorbid SUDs and psychiatric disorders, those with chronic pain, and at-risk children whose parents abuse opiates. Traditional addiction treatment programs typically do not address patients with complex conditions or special populations, such as adolescents or pregnant women with substance use issues. Evidence-based approaches such as Screening, Brief Intervention, and Referral to Treatment (SBIRT), Integrated Dual Diagnosis Treatment (IDDT), and prevention approaches that target students in middle schools and high schools need to be more widely available. 

Improve education on opioid prescribing   
Responsible opioid prescribing for clinicians should include education about the regular use of prescription drug monitoring programs, urine drug screening, avoiding co-prescription of opioids with sedative-hypnotic medications, and better linkage with addiction treatment. 

Treat comorbid psychiatric conditions 
It is critical to both identify and effectively treat underlying affective, anxiety, and psychotic disorders in patients with SUDs. Anxiety, depression, and emotional dysregulation often contribute to worsening substance abuse, abuse of prescription drugs, diversion of prescribed drugs, and an increased risk of overdoses and suicides. Effective treatment of comorbid psychiatric conditions also may reduce relapses.  

Increase research on causes and treatments 
Through research, we must expand our knowledge to better understand the factors that contribute to this epidemic and develop better treatments. These efforts may allow for the development of prevention mechanisms. For example, a recent study found that the continued use of opioid medications after an overdose was associated with a high risk of a repeated overdosecall out material?.¹⁷ At the end of a 2-year observation, 17% (confidence interval [CI]: 14% to 20%) of patients receiving a high daily dosage of a prescribed opioid had a repeat overdose compared with 15% (CI: 10% to 21%) of those receiving a moderate dosage, 9% (CI: 6% to 14%) of those receiving a low dosage, and 8% (CI: 6% to 11%) of those receiving no opioids.¹⁷ Of the patients who overdosed on prescribed opiates, 30% switched to a new prescriber after their overdose, many of whom may not have been aware of the previous overdose. From a public health perspective, it would make sense for prescribers to know of prior opioid and/or benzodiazepine overdoses. This could be reported by emergency department clinicians, law enforcement, and hospitals into a prescription drug monitoring program, which is readily available to prescribers in most states. 

Acknowledgment 
The authors thank Scott Proescholdbell, MPH, Injury and Violence Prevention Branch, Chronic Disease and Injury Section, Division of Public Health, North Carolina Department of Health and Human Services, for his assistance. 

Bottom Line

The collision of the coronavirus disease 2019 pandemic and the drug overdose epidemic has highlighted the urgent need for health care professionals to optimize care for individuals with substance use disorders. Suggested interventions include enhancing access to medication-assisted treatment and virtual treatment, improving education about naloxone and safe opioid prescribing practices, and diverting at-risk patients from the criminal justice system to interventions that focus on treatment.

Mr. S, age 64, presents for an outpatient follow-up after a recent hospital discharge for alcohol detoxification. He reports a long history of alcohol use, which has resulted in numerous hospital admissions. He has recently been receiving care from a gastroenterologist because the results of laboratory testing suggested hepatic impairment (Table 1). Mr. S says that a friend of his was able to stop drinking by taking a medication, and he wonders if he can be prescribed a medication to help him as well.

A chart review shows that Mr. S recently underwent paracentesis, during which 6 liters of fluid were removed. Additionally, an abdominal ultrasound confirmed hepatic cirrhosis.

According to the World Health Organization, alcohol consumption contributes to 3 million deaths annually.² The highest proportion of these deaths (21.3%) is due to alcohol-associated gastrointestinal complications, including alcoholic and infectious hepatitis, pancreatitis, and cirrhosis. Because the liver is the primary site of ethanol metabolism, it sustains the greatest degree of tissue injury with heavy alcohol consumption. Additionally, the association of harmful use of alcohol with risky sexual behavior may partially explain the higher prevalence of viral hepatitis among persons with alcohol use disorder (AUD) compared with the general population. Alcoholic liver disease (ALD) progresses through several stages, beginning with hepatic steatosis and progressing through alcohol-related hepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.³

Liver markers of alcohol use

Although biological markers can be used in clinical practice to screen and monitor for alcohol abuse, making a diagnosis of ALD can be challenging. Typically, a history of heavy alcohol consumption in addition to certain physical signs and laboratory tests for liver disease are the best indicators of ALD. However, the clinical assessment can be confounded by patients who deny or minimize how much alcohol they have consumed. Furthermore, physical and laboratory findings may not be specific to ALD.

Liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), have historically been used as the basis of diagnosing ALD. In addition to elevated bilirubin and evidence of macrocytic anemia, elevations in these enzymes may suggest heavy alcohol use, but these values alone are inadequate to establish ALD. Gamma-glutamyltransferase is found in cell membranes of several body tissues, including the liver and spleen, and therefore is not specific to liver damage. However, elevated GGT is the best indicator of excessive alcohol consumption because it has greater sensitivity than AST and ALT.^1,3,4

Although these biomarkers are helpful in diagnosing ALD, they lose some of their utility in patients with advanced liver disease. Patients with severe liver dysfunction may not have elevated serum aminotransferase levels because the degree of liver enzyme elevation does not correlate well with the severity of ALD. For example, patients with advanced cirrhosis may have liver enzyme levels that appear normal. However, the pattern of elevation in transaminases can be helpful in making a diagnosis of liver dysfunction; using the ratio of AST to ALT may aid in diagnosing ALD, because AST is elevated more than twice that of ALT in >80% of patients with ALD.^1,3,4

Table 2^1,3,4 shows the progression of ALD from steatohepatitis to alcoholic hepatitis to cirrhosis. In steatohepatitis, transaminitis is present but all other biomarkers normal. In alcoholic hepatitis, transaminitis is present along with elevated alkaline phosphatase, elevated bilirubin, and elevated international normalized ratio (INR). In alcoholic cirrhosis, the AST-to-ALT ratio is >2, and hypoalbuminemia, hyperbilirubinemia, and coagulopathy (evidenced by elevated INR) are present, consistent with long-term liver damage.^1,3,4

Continue to: FDA-approved medications

FDA-approved medications

Three medications—acamprosate, naltrexone, and disulfiram—currently are FDA-approved for treating AUD.^5,6 Additionally, several other medications have shown varying levels of efficacy in treating patients with AUD but are not FDA-approved for this indication (Table 3).^5-8

Acamprosate is thought to create a balance of inhibitor and excitatory neurotransmitters by functioning as a glutamate antagonist and gamma-aminobutyric acid (GABA) agonist. This is speculated to aid in abstinence from alcohol. Data suggests that acamprosate may be more effective for maintaining abstinence than for inducing remission in individuals who have not yet detoxified from alcohol. Because of its renal excretion, acamprosate is the only FDA-approved medication for AUD that is not associated with liver toxicity. The most commonly reported adverse effect with acamprosate use is diarrhea.

Naltrexone, a mu-opioid receptor antagonist, is available in both tablet and long-acting IM injection formulations. Naltrexone blocks the binding of endorphins created by alcohol consumption to opioid receptors. This results in diminished dopamine release and is speculated to decrease reward and positive reinforcement with alcohol consumption, leading to fewer heavy drinking days. Due to hepatic metabolism, naltrexone use carries a risk of liver injury. Cases of hepatitis and clinically significant liver dysfunction as well as transient, asymptomatic, hepatic transaminase elevations have been observed in patients who receive naltrexone. Because of the absence of first-pass metabolism, long-acting IM naltrexone may produce less hepatotoxicity than the oral formulation. When the FDA approved both formulations of naltrexone, a “black-box” warning was issued concerning the risk of liver damage; however, these warnings have since been removed from their respective prescribing information.

Disulfiram inhibits acetaldehyde dehydrogenase, resulting in elevated acetaldehyde concentrations after consuming alcohol. In theory, this medication reduces a person’s desire to drink due to the negative physiological and physical effects associated with increased acetaldehyde, including hypotension, flushing, nausea, and vomiting. Although most of these reactions are short-lived, disulfiram can induce hepatotoxicity and liver failure that may prove fatal. Disulfiram should be avoided in patients with advanced ALD.

Off-label medications for AUD

Additional pharmacotherapeutic agents have been evaluated in patients with AUD. Baclofen, topiramate, gabapentin, and ondansetron have shown varying levels of efficacy and pose minimal concern in patients with ALD.

Continue to: Baclofen

Baclofen. Although findings are conflicting, baclofen is the only agent that has been specifically studied for treating AUD in patients with ALD. A GABA B receptor antagonist, baclofen is currently FDA-approved for treating spasticity. In a series of open-label and double-blind studies, baclofen has been shown to effectively reduce alcohol intake, promote abstinence, and prevent relapse.^5,6 Further studies identified a possible dose-related response, noting that 20 mg taken 3 times daily may confer additional response over 10 mg taken 3 times daily.^5,6 Conversely, the ALPADIR study failed to demonstrate superiority of baclofen vs placebo in the maintenance of abstinence from alcohol despite dosing at 180 mg/d.⁹ This study did, however, find a significant reduction in alcohol craving in favor of baclofen.⁹ Further, in a randomized controlled trial (RCT) conducted in veterans with chronic hepatitis C, baclofen 30 mg/d failed to show superiority over placebo with regard to increasing abstinence or reducing alcohol use.¹⁰

Topiramate. A recent meta-analysis found that topiramate use may result in fewer drinking days, heavy drinking days, and number of drinks per drinking day.⁷ Additionally, topiramate has demonstrated a statistically significant reduction in alcohol craving as well as the ability to decrease all liver function test values.⁵ This agent should be used with caution in patients with hepatic encephalopathy because the adverse cognitive effects associated with topiramate may confound the clinical course and treatment of such.

Gabapentin. The use of gabapentin to treat patients with AUD is supported by multiple RCTs. In studies that evaluated dose-related response, higher doses of gabapentin (up to 1,800 mg/d) showed greater efficacy than lower doses (ie, 900 mg/d).⁸ Because gabapentin does not undergo hepatic metabolism, its use in patients with ALD is considered safe. Although the abuse potential of gabapentin is less defined in patients with AUD, there have been reports of abuse in other high-risk populations (ie, those with opioid use disorder, incarcerated persons, and those who misuse prescriptions recreationally).⁸

Ondansetron is speculated to decrease the reward from alcohol via the down-regulation of dopaminergic neurons. Studies examining ondansetron for patients with AUD have found that it decreases alcohol cravings in those with early-onset alcoholism (initial onset at age ≤25), but not in late-onset alcoholism (initial onset at age >25).⁵ However, the ondansetron doses used in these trials were very low (4 mcg/kg), and those doses are not available commercially.⁵

CASE CONTINUED

Following a discussion of available pharma­cotherapeutic options for AUD, Mr. S is started on baclofen, 10 mg 3 times daily, with plans for dose titration. At a 2-week follow-up appointment, Mr. S reports that he had not been taking baclofen as often as instructed; however, he denies further alcohol consumption and re-commits to baclofen treatment. Unfortunately, Mr. S is soon admitted to hospice care due to continued decompensation and is unable to attend any additional outpatient follow-up appointments. Three months after his initial outpatient contact, Mr. S dies due to alcoholic cirrhosis.

Related Resources

• Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-related liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306-333.
• Murail AR, Carey WD. Disease management. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. Cleveland Clinic Center for Continuing Education. Updated August 2017. www.clevelandclinicmeded. com/medicalpubs/diseasemanagement/hepatology/ guide-to-common-liver-tests/

Drug Brand Names

Acamprosate • Campral
Baclofen • Lioresal
Disulfiram • Antabuse
Gabapentin • Neurontin
Naltrexone • Revia, Vivitrol
Ondansetron • Zofran
Topiramate • Topamax

Mr. S, age 64, presents for an outpatient follow-up after a recent hospital discharge for alcohol detoxification. He reports a long history of alcohol use, which has resulted in numerous hospital admissions. He has recently been receiving care from a gastroenterologist because the results of laboratory testing suggested hepatic impairment (Table 1). Mr. S says that a friend of his was able to stop drinking by taking a medication, and he wonders if he can be prescribed a medication to help him as well.

A chart review shows that Mr. S recently underwent paracentesis, during which 6 liters of fluid were removed. Additionally, an abdominal ultrasound confirmed hepatic cirrhosis.

According to the World Health Organization, alcohol consumption contributes to 3 million deaths annually.² The highest proportion of these deaths (21.3%) is due to alcohol-associated gastrointestinal complications, including alcoholic and infectious hepatitis, pancreatitis, and cirrhosis. Because the liver is the primary site of ethanol metabolism, it sustains the greatest degree of tissue injury with heavy alcohol consumption. Additionally, the association of harmful use of alcohol with risky sexual behavior may partially explain the higher prevalence of viral hepatitis among persons with alcohol use disorder (AUD) compared with the general population. Alcoholic liver disease (ALD) progresses through several stages, beginning with hepatic steatosis and progressing through alcohol-related hepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.³

Liver markers of alcohol use

Although biological markers can be used in clinical practice to screen and monitor for alcohol abuse, making a diagnosis of ALD can be challenging. Typically, a history of heavy alcohol consumption in addition to certain physical signs and laboratory tests for liver disease are the best indicators of ALD. However, the clinical assessment can be confounded by patients who deny or minimize how much alcohol they have consumed. Furthermore, physical and laboratory findings may not be specific to ALD.

Liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), have historically been used as the basis of diagnosing ALD. In addition to elevated bilirubin and evidence of macrocytic anemia, elevations in these enzymes may suggest heavy alcohol use, but these values alone are inadequate to establish ALD. Gamma-glutamyltransferase is found in cell membranes of several body tissues, including the liver and spleen, and therefore is not specific to liver damage. However, elevated GGT is the best indicator of excessive alcohol consumption because it has greater sensitivity than AST and ALT.^1,3,4

Although these biomarkers are helpful in diagnosing ALD, they lose some of their utility in patients with advanced liver disease. Patients with severe liver dysfunction may not have elevated serum aminotransferase levels because the degree of liver enzyme elevation does not correlate well with the severity of ALD. For example, patients with advanced cirrhosis may have liver enzyme levels that appear normal. However, the pattern of elevation in transaminases can be helpful in making a diagnosis of liver dysfunction; using the ratio of AST to ALT may aid in diagnosing ALD, because AST is elevated more than twice that of ALT in >80% of patients with ALD.^1,3,4

Table 2^1,3,4 shows the progression of ALD from steatohepatitis to alcoholic hepatitis to cirrhosis. In steatohepatitis, transaminitis is present but all other biomarkers normal. In alcoholic hepatitis, transaminitis is present along with elevated alkaline phosphatase, elevated bilirubin, and elevated international normalized ratio (INR). In alcoholic cirrhosis, the AST-to-ALT ratio is >2, and hypoalbuminemia, hyperbilirubinemia, and coagulopathy (evidenced by elevated INR) are present, consistent with long-term liver damage.^1,3,4

Continue to: FDA-approved medications

FDA-approved medications

Three medications—acamprosate, naltrexone, and disulfiram—currently are FDA-approved for treating AUD.^5,6 Additionally, several other medications have shown varying levels of efficacy in treating patients with AUD but are not FDA-approved for this indication (Table 3).^5-8

Acamprosate is thought to create a balance of inhibitor and excitatory neurotransmitters by functioning as a glutamate antagonist and gamma-aminobutyric acid (GABA) agonist. This is speculated to aid in abstinence from alcohol. Data suggests that acamprosate may be more effective for maintaining abstinence than for inducing remission in individuals who have not yet detoxified from alcohol. Because of its renal excretion, acamprosate is the only FDA-approved medication for AUD that is not associated with liver toxicity. The most commonly reported adverse effect with acamprosate use is diarrhea.

Naltrexone, a mu-opioid receptor antagonist, is available in both tablet and long-acting IM injection formulations. Naltrexone blocks the binding of endorphins created by alcohol consumption to opioid receptors. This results in diminished dopamine release and is speculated to decrease reward and positive reinforcement with alcohol consumption, leading to fewer heavy drinking days. Due to hepatic metabolism, naltrexone use carries a risk of liver injury. Cases of hepatitis and clinically significant liver dysfunction as well as transient, asymptomatic, hepatic transaminase elevations have been observed in patients who receive naltrexone. Because of the absence of first-pass metabolism, long-acting IM naltrexone may produce less hepatotoxicity than the oral formulation. When the FDA approved both formulations of naltrexone, a “black-box” warning was issued concerning the risk of liver damage; however, these warnings have since been removed from their respective prescribing information.

Disulfiram inhibits acetaldehyde dehydrogenase, resulting in elevated acetaldehyde concentrations after consuming alcohol. In theory, this medication reduces a person’s desire to drink due to the negative physiological and physical effects associated with increased acetaldehyde, including hypotension, flushing, nausea, and vomiting. Although most of these reactions are short-lived, disulfiram can induce hepatotoxicity and liver failure that may prove fatal. Disulfiram should be avoided in patients with advanced ALD.

Off-label medications for AUD

Additional pharmacotherapeutic agents have been evaluated in patients with AUD. Baclofen, topiramate, gabapentin, and ondansetron have shown varying levels of efficacy and pose minimal concern in patients with ALD.

Continue to: Baclofen

Baclofen. Although findings are conflicting, baclofen is the only agent that has been specifically studied for treating AUD in patients with ALD. A GABA B receptor antagonist, baclofen is currently FDA-approved for treating spasticity. In a series of open-label and double-blind studies, baclofen has been shown to effectively reduce alcohol intake, promote abstinence, and prevent relapse.^5,6 Further studies identified a possible dose-related response, noting that 20 mg taken 3 times daily may confer additional response over 10 mg taken 3 times daily.^5,6 Conversely, the ALPADIR study failed to demonstrate superiority of baclofen vs placebo in the maintenance of abstinence from alcohol despite dosing at 180 mg/d.⁹ This study did, however, find a significant reduction in alcohol craving in favor of baclofen.⁹ Further, in a randomized controlled trial (RCT) conducted in veterans with chronic hepatitis C, baclofen 30 mg/d failed to show superiority over placebo with regard to increasing abstinence or reducing alcohol use.¹⁰

Topiramate. A recent meta-analysis found that topiramate use may result in fewer drinking days, heavy drinking days, and number of drinks per drinking day.⁷ Additionally, topiramate has demonstrated a statistically significant reduction in alcohol craving as well as the ability to decrease all liver function test values.⁵ This agent should be used with caution in patients with hepatic encephalopathy because the adverse cognitive effects associated with topiramate may confound the clinical course and treatment of such.

Gabapentin. The use of gabapentin to treat patients with AUD is supported by multiple RCTs. In studies that evaluated dose-related response, higher doses of gabapentin (up to 1,800 mg/d) showed greater efficacy than lower doses (ie, 900 mg/d).⁸ Because gabapentin does not undergo hepatic metabolism, its use in patients with ALD is considered safe. Although the abuse potential of gabapentin is less defined in patients with AUD, there have been reports of abuse in other high-risk populations (ie, those with opioid use disorder, incarcerated persons, and those who misuse prescriptions recreationally).⁸

Ondansetron is speculated to decrease the reward from alcohol via the down-regulation of dopaminergic neurons. Studies examining ondansetron for patients with AUD have found that it decreases alcohol cravings in those with early-onset alcoholism (initial onset at age ≤25), but not in late-onset alcoholism (initial onset at age >25).⁵ However, the ondansetron doses used in these trials were very low (4 mcg/kg), and those doses are not available commercially.⁵

CASE CONTINUED

Following a discussion of available pharma­cotherapeutic options for AUD, Mr. S is started on baclofen, 10 mg 3 times daily, with plans for dose titration. At a 2-week follow-up appointment, Mr. S reports that he had not been taking baclofen as often as instructed; however, he denies further alcohol consumption and re-commits to baclofen treatment. Unfortunately, Mr. S is soon admitted to hospice care due to continued decompensation and is unable to attend any additional outpatient follow-up appointments. Three months after his initial outpatient contact, Mr. S dies due to alcoholic cirrhosis.

Related Resources

• Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-related liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306-333.
• Murail AR, Carey WD. Disease management. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. Cleveland Clinic Center for Continuing Education. Updated August 2017. www.clevelandclinicmeded. com/medicalpubs/diseasemanagement/hepatology/ guide-to-common-liver-tests/

Drug Brand Names

Acamprosate • Campral
Baclofen • Lioresal
Disulfiram • Antabuse
Gabapentin • Neurontin
Naltrexone • Revia, Vivitrol
Ondansetron • Zofran
Topiramate • Topamax

Mr. S, age 64, presents for an outpatient follow-up after a recent hospital discharge for alcohol detoxification. He reports a long history of alcohol use, which has resulted in numerous hospital admissions. He has recently been receiving care from a gastroenterologist because the results of laboratory testing suggested hepatic impairment (Table 1). Mr. S says that a friend of his was able to stop drinking by taking a medication, and he wonders if he can be prescribed a medication to help him as well.

A chart review shows that Mr. S recently underwent paracentesis, during which 6 liters of fluid were removed. Additionally, an abdominal ultrasound confirmed hepatic cirrhosis.

According to the World Health Organization, alcohol consumption contributes to 3 million deaths annually.² The highest proportion of these deaths (21.3%) is due to alcohol-associated gastrointestinal complications, including alcoholic and infectious hepatitis, pancreatitis, and cirrhosis. Because the liver is the primary site of ethanol metabolism, it sustains the greatest degree of tissue injury with heavy alcohol consumption. Additionally, the association of harmful use of alcohol with risky sexual behavior may partially explain the higher prevalence of viral hepatitis among persons with alcohol use disorder (AUD) compared with the general population. Alcoholic liver disease (ALD) progresses through several stages, beginning with hepatic steatosis and progressing through alcohol-related hepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.³

Liver markers of alcohol use

Although biological markers can be used in clinical practice to screen and monitor for alcohol abuse, making a diagnosis of ALD can be challenging. Typically, a history of heavy alcohol consumption in addition to certain physical signs and laboratory tests for liver disease are the best indicators of ALD. However, the clinical assessment can be confounded by patients who deny or minimize how much alcohol they have consumed. Furthermore, physical and laboratory findings may not be specific to ALD.

Liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), have historically been used as the basis of diagnosing ALD. In addition to elevated bilirubin and evidence of macrocytic anemia, elevations in these enzymes may suggest heavy alcohol use, but these values alone are inadequate to establish ALD. Gamma-glutamyltransferase is found in cell membranes of several body tissues, including the liver and spleen, and therefore is not specific to liver damage. However, elevated GGT is the best indicator of excessive alcohol consumption because it has greater sensitivity than AST and ALT.^1,3,4

Although these biomarkers are helpful in diagnosing ALD, they lose some of their utility in patients with advanced liver disease. Patients with severe liver dysfunction may not have elevated serum aminotransferase levels because the degree of liver enzyme elevation does not correlate well with the severity of ALD. For example, patients with advanced cirrhosis may have liver enzyme levels that appear normal. However, the pattern of elevation in transaminases can be helpful in making a diagnosis of liver dysfunction; using the ratio of AST to ALT may aid in diagnosing ALD, because AST is elevated more than twice that of ALT in >80% of patients with ALD.^1,3,4

Table 2^1,3,4 shows the progression of ALD from steatohepatitis to alcoholic hepatitis to cirrhosis. In steatohepatitis, transaminitis is present but all other biomarkers normal. In alcoholic hepatitis, transaminitis is present along with elevated alkaline phosphatase, elevated bilirubin, and elevated international normalized ratio (INR). In alcoholic cirrhosis, the AST-to-ALT ratio is >2, and hypoalbuminemia, hyperbilirubinemia, and coagulopathy (evidenced by elevated INR) are present, consistent with long-term liver damage.^1,3,4

Continue to: FDA-approved medications

FDA-approved medications

Three medications—acamprosate, naltrexone, and disulfiram—currently are FDA-approved for treating AUD.^5,6 Additionally, several other medications have shown varying levels of efficacy in treating patients with AUD but are not FDA-approved for this indication (Table 3).^5-8

Acamprosate is thought to create a balance of inhibitor and excitatory neurotransmitters by functioning as a glutamate antagonist and gamma-aminobutyric acid (GABA) agonist. This is speculated to aid in abstinence from alcohol. Data suggests that acamprosate may be more effective for maintaining abstinence than for inducing remission in individuals who have not yet detoxified from alcohol. Because of its renal excretion, acamprosate is the only FDA-approved medication for AUD that is not associated with liver toxicity. The most commonly reported adverse effect with acamprosate use is diarrhea.

Naltrexone, a mu-opioid receptor antagonist, is available in both tablet and long-acting IM injection formulations. Naltrexone blocks the binding of endorphins created by alcohol consumption to opioid receptors. This results in diminished dopamine release and is speculated to decrease reward and positive reinforcement with alcohol consumption, leading to fewer heavy drinking days. Due to hepatic metabolism, naltrexone use carries a risk of liver injury. Cases of hepatitis and clinically significant liver dysfunction as well as transient, asymptomatic, hepatic transaminase elevations have been observed in patients who receive naltrexone. Because of the absence of first-pass metabolism, long-acting IM naltrexone may produce less hepatotoxicity than the oral formulation. When the FDA approved both formulations of naltrexone, a “black-box” warning was issued concerning the risk of liver damage; however, these warnings have since been removed from their respective prescribing information.

Disulfiram inhibits acetaldehyde dehydrogenase, resulting in elevated acetaldehyde concentrations after consuming alcohol. In theory, this medication reduces a person’s desire to drink due to the negative physiological and physical effects associated with increased acetaldehyde, including hypotension, flushing, nausea, and vomiting. Although most of these reactions are short-lived, disulfiram can induce hepatotoxicity and liver failure that may prove fatal. Disulfiram should be avoided in patients with advanced ALD.

Off-label medications for AUD

Additional pharmacotherapeutic agents have been evaluated in patients with AUD. Baclofen, topiramate, gabapentin, and ondansetron have shown varying levels of efficacy and pose minimal concern in patients with ALD.

Continue to: Baclofen

Baclofen. Although findings are conflicting, baclofen is the only agent that has been specifically studied for treating AUD in patients with ALD. A GABA B receptor antagonist, baclofen is currently FDA-approved for treating spasticity. In a series of open-label and double-blind studies, baclofen has been shown to effectively reduce alcohol intake, promote abstinence, and prevent relapse.^5,6 Further studies identified a possible dose-related response, noting that 20 mg taken 3 times daily may confer additional response over 10 mg taken 3 times daily.^5,6 Conversely, the ALPADIR study failed to demonstrate superiority of baclofen vs placebo in the maintenance of abstinence from alcohol despite dosing at 180 mg/d.⁹ This study did, however, find a significant reduction in alcohol craving in favor of baclofen.⁹ Further, in a randomized controlled trial (RCT) conducted in veterans with chronic hepatitis C, baclofen 30 mg/d failed to show superiority over placebo with regard to increasing abstinence or reducing alcohol use.¹⁰

Topiramate. A recent meta-analysis found that topiramate use may result in fewer drinking days, heavy drinking days, and number of drinks per drinking day.⁷ Additionally, topiramate has demonstrated a statistically significant reduction in alcohol craving as well as the ability to decrease all liver function test values.⁵ This agent should be used with caution in patients with hepatic encephalopathy because the adverse cognitive effects associated with topiramate may confound the clinical course and treatment of such.

Gabapentin. The use of gabapentin to treat patients with AUD is supported by multiple RCTs. In studies that evaluated dose-related response, higher doses of gabapentin (up to 1,800 mg/d) showed greater efficacy than lower doses (ie, 900 mg/d).⁸ Because gabapentin does not undergo hepatic metabolism, its use in patients with ALD is considered safe. Although the abuse potential of gabapentin is less defined in patients with AUD, there have been reports of abuse in other high-risk populations (ie, those with opioid use disorder, incarcerated persons, and those who misuse prescriptions recreationally).⁸

Ondansetron is speculated to decrease the reward from alcohol via the down-regulation of dopaminergic neurons. Studies examining ondansetron for patients with AUD have found that it decreases alcohol cravings in those with early-onset alcoholism (initial onset at age ≤25), but not in late-onset alcoholism (initial onset at age >25).⁵ However, the ondansetron doses used in these trials were very low (4 mcg/kg), and those doses are not available commercially.⁵

CASE CONTINUED

Following a discussion of available pharma­cotherapeutic options for AUD, Mr. S is started on baclofen, 10 mg 3 times daily, with plans for dose titration. At a 2-week follow-up appointment, Mr. S reports that he had not been taking baclofen as often as instructed; however, he denies further alcohol consumption and re-commits to baclofen treatment. Unfortunately, Mr. S is soon admitted to hospice care due to continued decompensation and is unable to attend any additional outpatient follow-up appointments. Three months after his initial outpatient contact, Mr. S dies due to alcoholic cirrhosis.

Related Resources

• Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-related liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306-333.
• Murail AR, Carey WD. Disease management. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. Cleveland Clinic Center for Continuing Education. Updated August 2017. www.clevelandclinicmeded. com/medicalpubs/diseasemanagement/hepatology/ guide-to-common-liver-tests/

Drug Brand Names

Acamprosate • Campral
Baclofen • Lioresal
Disulfiram • Antabuse
Gabapentin • Neurontin
Naltrexone • Revia, Vivitrol
Ondansetron • Zofran
Topiramate • Topamax

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

A version of this article first appeared on Medscape.com.

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

A version of this article first appeared on Medscape.com.

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

A version of this article first appeared on Medscape.com.

Shared medical appointments (SMAs) are an acceptable way to receive treatment for opioid use disorder (OUD), new research suggests.

In a survey study, participants attending an urban outpatient buprenorphine clinic reported a high degree of satisfaction with SMAs. However, the majority also reported they preferred individual appointments.

Still, SMAs may serve a role in providing comprehensive care for certain subpopulations with OUD who are prone to isolation and may also increase capacity to treat more patients with a substance use disorder (SUD), said coinvestigator Serra Akyar, MD, Northwell Health Staten Island University Hospital, New York.

“By providing education and a forum for sharing, SMAs can lead to changes in behavior and enhance and reinforce coping and problem-solving skills,” Dr. Akyar said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

SMA vs. group therapy

SMA is not a form of group therapy, Dr. Akyar noted. Group therapy has a psychotherapy component and is led by a therapist. SMAs do not have a psychotherapeutic or a behavioral therapy component but provide education and an opportunity for sharing personal experiences of recovery.

“For example, the doctor participating in the group describes what happens in the brain to drive addiction and fellow participants share their personal anecdotes of recovery, including their struggles and successes,” Dr. Akyar said.

“While SMAs and group therapy seem similar, using the terms interchangeably would be incorrect given the differences in the type of care each group provides,” she added.

Recent research on SMAs for OUD is limited. Although previous studies have shown that the practice is highly acceptable and has comparable or better retention in care rates with buprenorphine versus individual appointments, these studies have been conducted in predominantly White populations and in suburban settings.

For the new study, the investigators wanted to examine how acceptable SMAs for OUD would be in an urban setting involving predominantly racial and ethnic minorities.

They administered a 15-minute survey to patients with OUD who were attending the Comprehensive Addiction Resources and Education Center, an outpatient psychiatry clinic located at New Jersey Medical School, from December 2019 to February 2020.

Of the 42 participants who initially consented, 39 completed the survey. The majority of the responders were Black (64.1%), had an annual income that was less than $20,000 (61.5%), and/or were unemployed or disabled (69.3%).

Most of the participants agreed or strongly agreed with the following statements:

• Scheduling appointments for SMAs is easy.
• I gain valuable information from the responses to other patients’ questions in SMAs.
• There is enough time for questions during SMAs.
• I gain valuable information from the doctor and social worker in SMAs.
• My medical needs are met during SMAs.
• I would recommend an SMA to other patients.
• Since starting SMAs, I find it easier to stick to my treatment plan.
• I have a lot of support outside of SMAs.
• People in SMAs give me the support I need to stick to my treatment plan.

Interestingly, despite the overall high satisfaction with SMAs, just 33% of participants said they preferred them to one-on-one visits, Dr. Akyar noted.

Further analyses showed that total satisfaction scores were positively associated with older age, being on disability, or being in retirement.
 

Bridging the gap

In a comment, Philip Wong, MD, New Jersey Medical School, Newark, noted that a more widespread use of SMAs could potentially bridge the treatment gap that currently exists in the United States.

“For providers, SMAs help reduce costs, improve productivity, prevent repeating of common advice, and increase outreach. These are all important at a time when the need for OUD treatment is increasing. This is especially true for places like Newark, which is one of the prime epicenters of the opioid epidemic,” said Dr. Wong.

Although he was not involved with this research, he and his colleagues recently conducted a literature review of publications relating to SMAs and found seven peer-reviewed articles. However, none was appropriately designed to compare SMAs with traditional one-on-one recovery treatment.

“We definitely need more clinical studies to further our understanding of SMAs as a tool for the medication-assisted treatment of opioid use disorder,” Dr. Wong said.

“There are currently a very limited number of physicians who can prescribe medication-assisted treatment in the first place. So, if that one provider can reach a larger community by doing these SMAs, then the potential is very great in terms of addressing the opioid epidemic,” he said.

David Kan, MD, chief medical officer of Bright Heart Health, San Ramon, Calif., agreed.

“SMAs are promising because they are efficient and allow more people to access treatment,” Dr. Kan said in an interview.

“Although the mechanism of SMA satisfaction is unclear, other research shows peer support and groups helpful for SUD treatment as a whole. SMA takes the best of many worlds and increases the potential number of patients treated for SUD,” he said.

Also asked to comment, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, said SMAs “are one of a number of important interventions that should be considered” in order to increase availability and access to medication providers for OUD.

However, more research is needed “to examine the impact on treatment uptake and patient and provider experiences,” said Dr. Lin.

Dr. Akyar, Dr. Wong, Dr. Kan, and Dr. Lin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Shared medical appointments (SMAs) are an acceptable way to receive treatment for opioid use disorder (OUD), new research suggests.

In a survey study, participants attending an urban outpatient buprenorphine clinic reported a high degree of satisfaction with SMAs. However, the majority also reported they preferred individual appointments.

Still, SMAs may serve a role in providing comprehensive care for certain subpopulations with OUD who are prone to isolation and may also increase capacity to treat more patients with a substance use disorder (SUD), said coinvestigator Serra Akyar, MD, Northwell Health Staten Island University Hospital, New York.

“By providing education and a forum for sharing, SMAs can lead to changes in behavior and enhance and reinforce coping and problem-solving skills,” Dr. Akyar said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

SMA vs. group therapy

SMA is not a form of group therapy, Dr. Akyar noted. Group therapy has a psychotherapy component and is led by a therapist. SMAs do not have a psychotherapeutic or a behavioral therapy component but provide education and an opportunity for sharing personal experiences of recovery.

“For example, the doctor participating in the group describes what happens in the brain to drive addiction and fellow participants share their personal anecdotes of recovery, including their struggles and successes,” Dr. Akyar said.

“While SMAs and group therapy seem similar, using the terms interchangeably would be incorrect given the differences in the type of care each group provides,” she added.

Recent research on SMAs for OUD is limited. Although previous studies have shown that the practice is highly acceptable and has comparable or better retention in care rates with buprenorphine versus individual appointments, these studies have been conducted in predominantly White populations and in suburban settings.

For the new study, the investigators wanted to examine how acceptable SMAs for OUD would be in an urban setting involving predominantly racial and ethnic minorities.

They administered a 15-minute survey to patients with OUD who were attending the Comprehensive Addiction Resources and Education Center, an outpatient psychiatry clinic located at New Jersey Medical School, from December 2019 to February 2020.

Of the 42 participants who initially consented, 39 completed the survey. The majority of the responders were Black (64.1%), had an annual income that was less than $20,000 (61.5%), and/or were unemployed or disabled (69.3%).

Most of the participants agreed or strongly agreed with the following statements:

• Scheduling appointments for SMAs is easy.
• I gain valuable information from the responses to other patients’ questions in SMAs.
• There is enough time for questions during SMAs.
• I gain valuable information from the doctor and social worker in SMAs.
• My medical needs are met during SMAs.
• I would recommend an SMA to other patients.
• Since starting SMAs, I find it easier to stick to my treatment plan.
• I have a lot of support outside of SMAs.
• People in SMAs give me the support I need to stick to my treatment plan.

Interestingly, despite the overall high satisfaction with SMAs, just 33% of participants said they preferred them to one-on-one visits, Dr. Akyar noted.

Further analyses showed that total satisfaction scores were positively associated with older age, being on disability, or being in retirement.
 

Bridging the gap

In a comment, Philip Wong, MD, New Jersey Medical School, Newark, noted that a more widespread use of SMAs could potentially bridge the treatment gap that currently exists in the United States.

“For providers, SMAs help reduce costs, improve productivity, prevent repeating of common advice, and increase outreach. These are all important at a time when the need for OUD treatment is increasing. This is especially true for places like Newark, which is one of the prime epicenters of the opioid epidemic,” said Dr. Wong.

Although he was not involved with this research, he and his colleagues recently conducted a literature review of publications relating to SMAs and found seven peer-reviewed articles. However, none was appropriately designed to compare SMAs with traditional one-on-one recovery treatment.

“We definitely need more clinical studies to further our understanding of SMAs as a tool for the medication-assisted treatment of opioid use disorder,” Dr. Wong said.

“There are currently a very limited number of physicians who can prescribe medication-assisted treatment in the first place. So, if that one provider can reach a larger community by doing these SMAs, then the potential is very great in terms of addressing the opioid epidemic,” he said.

David Kan, MD, chief medical officer of Bright Heart Health, San Ramon, Calif., agreed.

“SMAs are promising because they are efficient and allow more people to access treatment,” Dr. Kan said in an interview.

“Although the mechanism of SMA satisfaction is unclear, other research shows peer support and groups helpful for SUD treatment as a whole. SMA takes the best of many worlds and increases the potential number of patients treated for SUD,” he said.

Also asked to comment, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, said SMAs “are one of a number of important interventions that should be considered” in order to increase availability and access to medication providers for OUD.

However, more research is needed “to examine the impact on treatment uptake and patient and provider experiences,” said Dr. Lin.

Dr. Akyar, Dr. Wong, Dr. Kan, and Dr. Lin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Shared medical appointments (SMAs) are an acceptable way to receive treatment for opioid use disorder (OUD), new research suggests.

In a survey study, participants attending an urban outpatient buprenorphine clinic reported a high degree of satisfaction with SMAs. However, the majority also reported they preferred individual appointments.

Still, SMAs may serve a role in providing comprehensive care for certain subpopulations with OUD who are prone to isolation and may also increase capacity to treat more patients with a substance use disorder (SUD), said coinvestigator Serra Akyar, MD, Northwell Health Staten Island University Hospital, New York.

“By providing education and a forum for sharing, SMAs can lead to changes in behavior and enhance and reinforce coping and problem-solving skills,” Dr. Akyar said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

SMA vs. group therapy

SMA is not a form of group therapy, Dr. Akyar noted. Group therapy has a psychotherapy component and is led by a therapist. SMAs do not have a psychotherapeutic or a behavioral therapy component but provide education and an opportunity for sharing personal experiences of recovery.

“For example, the doctor participating in the group describes what happens in the brain to drive addiction and fellow participants share their personal anecdotes of recovery, including their struggles and successes,” Dr. Akyar said.

“While SMAs and group therapy seem similar, using the terms interchangeably would be incorrect given the differences in the type of care each group provides,” she added.

Recent research on SMAs for OUD is limited. Although previous studies have shown that the practice is highly acceptable and has comparable or better retention in care rates with buprenorphine versus individual appointments, these studies have been conducted in predominantly White populations and in suburban settings.

For the new study, the investigators wanted to examine how acceptable SMAs for OUD would be in an urban setting involving predominantly racial and ethnic minorities.

They administered a 15-minute survey to patients with OUD who were attending the Comprehensive Addiction Resources and Education Center, an outpatient psychiatry clinic located at New Jersey Medical School, from December 2019 to February 2020.

Of the 42 participants who initially consented, 39 completed the survey. The majority of the responders were Black (64.1%), had an annual income that was less than $20,000 (61.5%), and/or were unemployed or disabled (69.3%).

Most of the participants agreed or strongly agreed with the following statements:

• Scheduling appointments for SMAs is easy.
• I gain valuable information from the responses to other patients’ questions in SMAs.
• There is enough time for questions during SMAs.
• I gain valuable information from the doctor and social worker in SMAs.
• My medical needs are met during SMAs.
• I would recommend an SMA to other patients.
• Since starting SMAs, I find it easier to stick to my treatment plan.
• I have a lot of support outside of SMAs.
• People in SMAs give me the support I need to stick to my treatment plan.

Interestingly, despite the overall high satisfaction with SMAs, just 33% of participants said they preferred them to one-on-one visits, Dr. Akyar noted.

Further analyses showed that total satisfaction scores were positively associated with older age, being on disability, or being in retirement.
 

Bridging the gap

In a comment, Philip Wong, MD, New Jersey Medical School, Newark, noted that a more widespread use of SMAs could potentially bridge the treatment gap that currently exists in the United States.

“For providers, SMAs help reduce costs, improve productivity, prevent repeating of common advice, and increase outreach. These are all important at a time when the need for OUD treatment is increasing. This is especially true for places like Newark, which is one of the prime epicenters of the opioid epidemic,” said Dr. Wong.

Although he was not involved with this research, he and his colleagues recently conducted a literature review of publications relating to SMAs and found seven peer-reviewed articles. However, none was appropriately designed to compare SMAs with traditional one-on-one recovery treatment.

“We definitely need more clinical studies to further our understanding of SMAs as a tool for the medication-assisted treatment of opioid use disorder,” Dr. Wong said.

“There are currently a very limited number of physicians who can prescribe medication-assisted treatment in the first place. So, if that one provider can reach a larger community by doing these SMAs, then the potential is very great in terms of addressing the opioid epidemic,” he said.

David Kan, MD, chief medical officer of Bright Heart Health, San Ramon, Calif., agreed.

“SMAs are promising because they are efficient and allow more people to access treatment,” Dr. Kan said in an interview.

“Although the mechanism of SMA satisfaction is unclear, other research shows peer support and groups helpful for SUD treatment as a whole. SMA takes the best of many worlds and increases the potential number of patients treated for SUD,” he said.

Also asked to comment, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, said SMAs “are one of a number of important interventions that should be considered” in order to increase availability and access to medication providers for OUD.

However, more research is needed “to examine the impact on treatment uptake and patient and provider experiences,” said Dr. Lin.

Dr. Akyar, Dr. Wong, Dr. Kan, and Dr. Lin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mr. P, age 65, has a history of major depressive disorder (MDD), generalized anxiety disorder, and social phobia. Mr. P’s personality is high in neuroticism and he has often responded to new situations with feelings of impending doom. For him, fear, anxious rumination, helplessness, and catastrophizing are familiar mental processes.

When he was in his 30s, Mr. P had a severe major depressive episode with suicidal ideation and sought care from a psychiatrist. He began a treatment program of psychotherapy and concomitant psychopharmacotherapy with consecutive trials of fluoxetine, sertraline, and amitriptyline, each of an adequate dose and duration. With each medication, Mr. P experienced new adverse effects, including nausea, constipation, tremors, and headache. His psychiatrist transitioned him to bupropion, which helped Mr. P most. For the next several decades, Mr. P continued to experience low-grade depressive symptoms with intermittent exacerbation to mild-to-moderate major depressive episodes, but he remained adherent to his medication and continued psychotherapy.

Shortly after his 65th birthday, Mr. P experiences progressively worsening nausea and abdominal pain. Initially, he assumes the symptoms are secondary to anxiety. Taking his psychiatrist’s advice, Mr. P visits his primary care physician. A work-up reveals that Mr. P has advanced pancreatic cancer, and an oncologist estimates Mr. P has 6 months of life remaining.

Following his cancer diagnosis, Mr. P quickly develops symptoms of MDD despite continuing to take bupropion. Within a week he becomes withdrawn and hopeless, and thinks about ending his life “before God does.” His psychiatrist urges Mr. P to contact the local academic medical center because it is conducting a trial of a “new” drug, psilocybin, to treat anxiety and depression in patients with terminal illness.

Beginning in the 1940s, a growing body of scientific evidence suggested that psychedelic compounds such as lysergic acid diethylamide (LSD) could benefit individuals with various psychiatric maladies. Research interest in LSD and substances with similar effects persisted until the late 1960s. In response to the growing counterculture movement in the United States and the efforts of Harvard researchers Timothy Leary and Richard Alpert to popularize psychedelic drug use in the general population, in 1970 President Richard M. Nixon signed the Controlled Substances Act (CSA) into law. The CSA categorized LSD as a Schedule I drug, rendering its manufacture and distribution illegal. Research into the potential therapeutic benefits of LSD was effectively halted.¹ In recent decades, however, there has been a quiet but growing renaissance of scientific interest in the effects of psychedelics on a variety of conditions, including terminal illness–related anxiety and depression, treatment-resistant depression, and substance use disorders (SUDs). One example is psilocybin, which is currently undergoing Phase 2 and 3 clinical trials in North America and Europe for treatment-resistant depression.

As researchers have once again picked up the torch in the pursuit of psychedelic therapeutics, jurisdictions in the United States are also relaxing their stance on these drugs. In 2019 and early 2020, Denver, Oakland, and Santa Cruz became the first 3 cities in the United States to decriminalize the possession of various psychedelic substances.^2-4 With the passage of Measure 109 in November 2020, Oregon became the first state to decriminalize the use of psychedelic mushrooms in therapeutic settings.⁵ The combined forces of increased research and relaxed political concern related to psychedelics might make it possible for the FDA to approve their use for psychiatric conditions. Therefore, it is critical for psychiatrists to understand the psychopharmacology, range of effects, and potential risks and benefits of these agents. In this article, I describe what psychedelics are and how they work, summarize a few research findings about psilocybin, and offer a framework for psychedelic psychiatric practice in the years to come.

What are psychedelics?

Psychiatrist Humphry Osmond first coined the term “psychedelic” in 1957 at a meeting of the New York Academy of Sciences, where he was discussing his research on the effect of LSD on patients at the Weyburn Mental Hospital in Saskatchewan, Canada.⁶ Prior to 1957, LSD had been described as a “psycho­tomimetic” drug because it was believed to induce a state of psychosis similar to that experienced in schizophrenia. But LSD does not generally induce frank auditory hallucinations or clearly defined delusional beliefs. Osmond’s new term—derived from the Greek words psyche, meaning “mind,” and delos, meaning “to show”—referred to the “mind-manifesting” capacities of LSD and related drugs.⁶ Psychedelic drugs can cause an array of changes to an individual’s conscious experience, from relatively mild changes in visual perception to profound derangements in sense of self and reality.

Continue to: Before describing the effects...

Classic psychedelics vs other compounds

Before describing the effects of psychedelic drugs and how they may relate to their therapeutic potential, it is useful to define which compounds are considered “classic psychedelics.”

The classic psychedelics are substances that operate primarily through activation of the serotonin 5-hydroxytryptamine receptor 2A receptor (5-HT2A) (Table 1⁷). Many psychedelic drugs are derived from natural sources, including plants, fungi, and animals. For example, N, N-dimethyltryptamine (DMT), which is one of the most potent psychedelic compounds, is found in various plant species and can be imbibed in a tea known as ayahuasca, most commonly in the context of spiritual ceremonies.

How psychedelics work

Psychedelics can induce a spectrum of effects that are not necessarily dose-dependent. Mild effects of intoxication include altered sensory perception in visual, auditory, proprioceptive, and somatosensory spheres, including synesthesia. Progressively more severe changes include a distorted or eliminated perception or awareness of space, time, body, and self, resulting in derealization and depersonalization. Some of the most extreme alterations of consciousness reported by users include mystical or transcendent experiences of birth, giving birth, death, exchanging bodies with a nonhuman species, and meeting otherworldly beings.¹¹ In terms of neurophysiology, psychedelics cause altered cerebral blood flow and metabolism, increased connectivity between brain regions that do not typically communicate, and a reduction in the activity of a group of cortical structures called the default mode network (DMN).¹²

Continue to: Researchers hypothesize that...

Researchers hypothesize that the disruption of DMN activity may be a key mechanism accounting for psychedelics’ therapeutic effects in mental illness. The DMN is a group of structures that includes the posterior cingulate cortex, the medial prefrontal cortex, the angular gyrus, and other cortical areas that are active when an individual is not engaged in a particular mental task (for example, during mind wandering). It is thought to underlie introspection and to serve as an “orchestrator” of global brain function.¹³ Theoretically, then, by temporarily disrupting the neural circuits responsible for maintaining ingrained, negative thought and behavioral patterns, as observed in patients with depression or SUDs, psychedelics can help patients develop greater emotional and cognitive flexibility and identify new ways to view the world and to solve problems.

Evaluating psychedelics as therapeutic agents

The renaissance of research into psychedelics as therapeutic agents during the last 2 decades has produced some promising preliminary findings. In 2020, the American Psychiatric Association’s Work Group on Biomarkers and Novel Treatments published a review of the best evidence on the topic.¹⁴ Psilocybin is the most studied drug because compared with LSD, it carries less of a stigma and has a shorter duration of action. Psilocybin has been studied as a potential treatment for several psychiatric disorders, including terminal illness–related depression and anxiety, and SUDs.

Griffiths et al.¹⁵ In a double-blind randomized crossover study at Johns Hopkins School of Medicine, Griffiths et al¹⁵ administered a high dose (22 or 30 mg/70 kg) and a very low, placebo-like dose (1 or 3 mg/70 kg) of psilocybin at 2 separate sessions to 51 patients with terminal cancer and associated depressive and anxiety disorders. After 5 weeks, the participants assigned to one condition crossed over to the other condition. High-dose psilocybin had a significant effect on depression and anxiety symptoms within 5 weeks that persisted over 6 months of follow-up. At 6 months, 78% of participants experienced a response in depressive symptoms (≥50% decrease in GRID-Hamilton Depression Rating Scale [HAM-D-17] baseline scores) and 65% remitted (GRID-HAM-D-17 score ≤7). At 6 months, 83% of participants had a response in anxiety symptoms (≥50% decrease in Hamilton Rating Scale for Anxiety [HAM-A] baseline scores) and 57% remitted (HAM-A ≤7).

Johnson et al.^16,17 In an open-label pilot study¹⁶ and ≥12-month follow-up study,¹⁷ Johnson et al administered a moderate (20 mg/70 kg) and high (30 mg/70 kg) dose of psilocybin to 15 participants enrolled in a 15-week smoking session program. The psilocybin sessions were scheduled at Weeks 5 and 7, with an optional psilocybin session at Week 13. The sessions included nondirective support from program staff, but not smoking cessation content. Relying on laboratory-verified exhaled carbon monoxide and urine cotinine measures, researchers found an 80% abstinence rate at 6 months, a 67% abstinence rate at 12 months, and a 75% abstinence rate at 2.5 years.^16,17

Bogenschutz et al¹⁸ conducted a study of 10 patients who met DSM-IV criteria for alcohol dependence and had at least 2 heavy drinking days in the previous 30 days. They found that a 14-session treatment program that included 2 psilocybin-assisted psychotherapy sessions with dosages of 0.4 mg/kg resulted in a significant increase in self-reported alcohol abstinence at 4 weeks that persisted for 36 weeks.¹⁸

Although these studies were small, open-label, and had other methodologic flaws, their pilot work has led to larger-scale projects assessing psilocybin’s therapeutic potential. Psilocybin has also been studied for treatment-resistant depression and obsessive-compulsive disorder. Other clinical trials underway are investigating psilocybin for the treatment of cocaine and opioid use disorder, anorexia nervosa, and depression in Alzheimer’s disease.¹⁴ Although psilocybin is currently the best-studied psychedelic, there is some research demonstrating that LSD can also induce a persistent reduction in anxiety symptoms associated with terminal illness¹⁹ and that ayahuasca causes a rapid reduction in depressive symptoms that persists over 21 days.²⁰

Continue to: The future of psychedelic psychiatry...

The future of psychedelic psychiatry

If psychedelic compounds become approved for the treatment of psychiatric conditions, psychiatrists will likely be responsible for prescribing them and managing patients who receive them.²¹Table 2^11,21-24 summarizes practical considerations for psychiatrists who may someday be prescribing psychedelic drugs. Areas of psychedelic treatment in which psychiatric expertise is necessary include:

• screening for patients at increased risk for a challenging or adverse experience or “bad trip”
• conducting a thorough informed consent process in which the risks are discussed and the patient’s wishes regarding potential situations are elicited
• managing acute medical and psychiatric complications, including agitation and violent behavior
• ensuring the use of trained guides during sessions.

Psychiatrists who are interested in providing psychedelic-assisted therapy should understand the concept of “set and setting,” which was defined by Timothy Leary in the 1960s and is thought to play an important role in determining the types of experiences that arise during a psychedelic session.²⁵ “Set” refers to an individual’s mindset going into a session, and “setting” refers to the environment in which the session occurs. Typical elements of each are summarized in Table 3.⁷ Psychiatrists will play a critical role in assessing and preparing the “set” by screening patients appropriately, assessing patient goals, and providing a thorough informed consent procedure. Psychiatrists should also be mindful of the “setting,” providing a comfortable, safe, familiar environment and access to appropriate music and eyeshades, if desired. Due to time restraints, psychiatrists are not likely to be responsible for guiding patients through sessions, and should educate themselves about ethical practices of psychedelic guides,if they are in the position to hire guides.^23,24

CASE CONTINUED

Mr. P is enrolled in the academic medical center study assessing the effect of psilocybin on terminal illness-related anxiety and depression. During a 5-hour, 30-mg psilocybin session, he initially experiences distorted visual cues, with vivid, colorful geometric patterns collapsing into each other. He then loses the concepts and experience of time, space, and his body, as his visual distortions convert to darkness. After what seems like a decade within the darkness, he sees himself lying in a hospital bed with loved ones surrounding him. He watches himself take his last breaths and his family members weep as he dies. As he regains his senses, Mr. P feels that he is being reborn.

In the therapy sessions that follow the psychedelic session, Mr. P reports feeling “finally freed” from the fear, sadness, and anger that he has felt throughout his life. He comes to accept his impending death with gratitude and peace. In his final days, he no longer experiences depression or anxiety. Mr. P’s friends and family members comment that he seems to be the best version of himself in the months that lead up to his death.

Related Resources

• Nutt D. Psychedelic drugs-a new era in psychiatry? Dialogues Clin Neurosci. 2019;21(2):139-147.

• Garcia-Romeu A, Kersgaard B, Addy PH. Clinical applications of hallucinogens: a review. Exp Clin Psychopharmacol. 2016; 24(4):229-268.

Drug Brand Names

Amitriptyline • Amitril, Elavil
Bupropion • Wellbutrin
Fluoxetine • Prozac
Sertraline • Zoloft

Bottom Line

Psychedelics are a class of consciousness-altering agents that have become a potentially promising source of new treatments for psychiatric illness. Although more evidence is needed, compounds such as psilocybin may one day become FDAapproved for conditions such as terminal illness–related depression and anxiety, and substance use disorders. When this occurs, psychiatrists should be responsible for prescribing psychedelics and managing patients who receive treatment.

Mr. P, age 65, has a history of major depressive disorder (MDD), generalized anxiety disorder, and social phobia. Mr. P’s personality is high in neuroticism and he has often responded to new situations with feelings of impending doom. For him, fear, anxious rumination, helplessness, and catastrophizing are familiar mental processes.

When he was in his 30s, Mr. P had a severe major depressive episode with suicidal ideation and sought care from a psychiatrist. He began a treatment program of psychotherapy and concomitant psychopharmacotherapy with consecutive trials of fluoxetine, sertraline, and amitriptyline, each of an adequate dose and duration. With each medication, Mr. P experienced new adverse effects, including nausea, constipation, tremors, and headache. His psychiatrist transitioned him to bupropion, which helped Mr. P most. For the next several decades, Mr. P continued to experience low-grade depressive symptoms with intermittent exacerbation to mild-to-moderate major depressive episodes, but he remained adherent to his medication and continued psychotherapy.

Shortly after his 65th birthday, Mr. P experiences progressively worsening nausea and abdominal pain. Initially, he assumes the symptoms are secondary to anxiety. Taking his psychiatrist’s advice, Mr. P visits his primary care physician. A work-up reveals that Mr. P has advanced pancreatic cancer, and an oncologist estimates Mr. P has 6 months of life remaining.

Following his cancer diagnosis, Mr. P quickly develops symptoms of MDD despite continuing to take bupropion. Within a week he becomes withdrawn and hopeless, and thinks about ending his life “before God does.” His psychiatrist urges Mr. P to contact the local academic medical center because it is conducting a trial of a “new” drug, psilocybin, to treat anxiety and depression in patients with terminal illness.

Beginning in the 1940s, a growing body of scientific evidence suggested that psychedelic compounds such as lysergic acid diethylamide (LSD) could benefit individuals with various psychiatric maladies. Research interest in LSD and substances with similar effects persisted until the late 1960s. In response to the growing counterculture movement in the United States and the efforts of Harvard researchers Timothy Leary and Richard Alpert to popularize psychedelic drug use in the general population, in 1970 President Richard M. Nixon signed the Controlled Substances Act (CSA) into law. The CSA categorized LSD as a Schedule I drug, rendering its manufacture and distribution illegal. Research into the potential therapeutic benefits of LSD was effectively halted.¹ In recent decades, however, there has been a quiet but growing renaissance of scientific interest in the effects of psychedelics on a variety of conditions, including terminal illness–related anxiety and depression, treatment-resistant depression, and substance use disorders (SUDs). One example is psilocybin, which is currently undergoing Phase 2 and 3 clinical trials in North America and Europe for treatment-resistant depression.

As researchers have once again picked up the torch in the pursuit of psychedelic therapeutics, jurisdictions in the United States are also relaxing their stance on these drugs. In 2019 and early 2020, Denver, Oakland, and Santa Cruz became the first 3 cities in the United States to decriminalize the possession of various psychedelic substances.^2-4 With the passage of Measure 109 in November 2020, Oregon became the first state to decriminalize the use of psychedelic mushrooms in therapeutic settings.⁵ The combined forces of increased research and relaxed political concern related to psychedelics might make it possible for the FDA to approve their use for psychiatric conditions. Therefore, it is critical for psychiatrists to understand the psychopharmacology, range of effects, and potential risks and benefits of these agents. In this article, I describe what psychedelics are and how they work, summarize a few research findings about psilocybin, and offer a framework for psychedelic psychiatric practice in the years to come.

What are psychedelics?

Psychiatrist Humphry Osmond first coined the term “psychedelic” in 1957 at a meeting of the New York Academy of Sciences, where he was discussing his research on the effect of LSD on patients at the Weyburn Mental Hospital in Saskatchewan, Canada.⁶ Prior to 1957, LSD had been described as a “psycho­tomimetic” drug because it was believed to induce a state of psychosis similar to that experienced in schizophrenia. But LSD does not generally induce frank auditory hallucinations or clearly defined delusional beliefs. Osmond’s new term—derived from the Greek words psyche, meaning “mind,” and delos, meaning “to show”—referred to the “mind-manifesting” capacities of LSD and related drugs.⁶ Psychedelic drugs can cause an array of changes to an individual’s conscious experience, from relatively mild changes in visual perception to profound derangements in sense of self and reality.

Continue to: Before describing the effects...

Classic psychedelics vs other compounds

Before describing the effects of psychedelic drugs and how they may relate to their therapeutic potential, it is useful to define which compounds are considered “classic psychedelics.”

The classic psychedelics are substances that operate primarily through activation of the serotonin 5-hydroxytryptamine receptor 2A receptor (5-HT2A) (Table 1⁷). Many psychedelic drugs are derived from natural sources, including plants, fungi, and animals. For example, N, N-dimethyltryptamine (DMT), which is one of the most potent psychedelic compounds, is found in various plant species and can be imbibed in a tea known as ayahuasca, most commonly in the context of spiritual ceremonies.

How psychedelics work

Psychedelics can induce a spectrum of effects that are not necessarily dose-dependent. Mild effects of intoxication include altered sensory perception in visual, auditory, proprioceptive, and somatosensory spheres, including synesthesia. Progressively more severe changes include a distorted or eliminated perception or awareness of space, time, body, and self, resulting in derealization and depersonalization. Some of the most extreme alterations of consciousness reported by users include mystical or transcendent experiences of birth, giving birth, death, exchanging bodies with a nonhuman species, and meeting otherworldly beings.¹¹ In terms of neurophysiology, psychedelics cause altered cerebral blood flow and metabolism, increased connectivity between brain regions that do not typically communicate, and a reduction in the activity of a group of cortical structures called the default mode network (DMN).¹²

Continue to: Researchers hypothesize that...

Researchers hypothesize that the disruption of DMN activity may be a key mechanism accounting for psychedelics’ therapeutic effects in mental illness. The DMN is a group of structures that includes the posterior cingulate cortex, the medial prefrontal cortex, the angular gyrus, and other cortical areas that are active when an individual is not engaged in a particular mental task (for example, during mind wandering). It is thought to underlie introspection and to serve as an “orchestrator” of global brain function.¹³ Theoretically, then, by temporarily disrupting the neural circuits responsible for maintaining ingrained, negative thought and behavioral patterns, as observed in patients with depression or SUDs, psychedelics can help patients develop greater emotional and cognitive flexibility and identify new ways to view the world and to solve problems.

Evaluating psychedelics as therapeutic agents

The renaissance of research into psychedelics as therapeutic agents during the last 2 decades has produced some promising preliminary findings. In 2020, the American Psychiatric Association’s Work Group on Biomarkers and Novel Treatments published a review of the best evidence on the topic.¹⁴ Psilocybin is the most studied drug because compared with LSD, it carries less of a stigma and has a shorter duration of action. Psilocybin has been studied as a potential treatment for several psychiatric disorders, including terminal illness–related depression and anxiety, and SUDs.

Griffiths et al.¹⁵ In a double-blind randomized crossover study at Johns Hopkins School of Medicine, Griffiths et al¹⁵ administered a high dose (22 or 30 mg/70 kg) and a very low, placebo-like dose (1 or 3 mg/70 kg) of psilocybin at 2 separate sessions to 51 patients with terminal cancer and associated depressive and anxiety disorders. After 5 weeks, the participants assigned to one condition crossed over to the other condition. High-dose psilocybin had a significant effect on depression and anxiety symptoms within 5 weeks that persisted over 6 months of follow-up. At 6 months, 78% of participants experienced a response in depressive symptoms (≥50% decrease in GRID-Hamilton Depression Rating Scale [HAM-D-17] baseline scores) and 65% remitted (GRID-HAM-D-17 score ≤7). At 6 months, 83% of participants had a response in anxiety symptoms (≥50% decrease in Hamilton Rating Scale for Anxiety [HAM-A] baseline scores) and 57% remitted (HAM-A ≤7).

Johnson et al.^16,17 In an open-label pilot study¹⁶ and ≥12-month follow-up study,¹⁷ Johnson et al administered a moderate (20 mg/70 kg) and high (30 mg/70 kg) dose of psilocybin to 15 participants enrolled in a 15-week smoking session program. The psilocybin sessions were scheduled at Weeks 5 and 7, with an optional psilocybin session at Week 13. The sessions included nondirective support from program staff, but not smoking cessation content. Relying on laboratory-verified exhaled carbon monoxide and urine cotinine measures, researchers found an 80% abstinence rate at 6 months, a 67% abstinence rate at 12 months, and a 75% abstinence rate at 2.5 years.^16,17

Bogenschutz et al¹⁸ conducted a study of 10 patients who met DSM-IV criteria for alcohol dependence and had at least 2 heavy drinking days in the previous 30 days. They found that a 14-session treatment program that included 2 psilocybin-assisted psychotherapy sessions with dosages of 0.4 mg/kg resulted in a significant increase in self-reported alcohol abstinence at 4 weeks that persisted for 36 weeks.¹⁸

Although these studies were small, open-label, and had other methodologic flaws, their pilot work has led to larger-scale projects assessing psilocybin’s therapeutic potential. Psilocybin has also been studied for treatment-resistant depression and obsessive-compulsive disorder. Other clinical trials underway are investigating psilocybin for the treatment of cocaine and opioid use disorder, anorexia nervosa, and depression in Alzheimer’s disease.¹⁴ Although psilocybin is currently the best-studied psychedelic, there is some research demonstrating that LSD can also induce a persistent reduction in anxiety symptoms associated with terminal illness¹⁹ and that ayahuasca causes a rapid reduction in depressive symptoms that persists over 21 days.²⁰

Continue to: The future of psychedelic psychiatry...

The future of psychedelic psychiatry

If psychedelic compounds become approved for the treatment of psychiatric conditions, psychiatrists will likely be responsible for prescribing them and managing patients who receive them.²¹Table 2^11,21-24 summarizes practical considerations for psychiatrists who may someday be prescribing psychedelic drugs. Areas of psychedelic treatment in which psychiatric expertise is necessary include:

• screening for patients at increased risk for a challenging or adverse experience or “bad trip”
• conducting a thorough informed consent process in which the risks are discussed and the patient’s wishes regarding potential situations are elicited
• managing acute medical and psychiatric complications, including agitation and violent behavior
• ensuring the use of trained guides during sessions.

Psychiatrists who are interested in providing psychedelic-assisted therapy should understand the concept of “set and setting,” which was defined by Timothy Leary in the 1960s and is thought to play an important role in determining the types of experiences that arise during a psychedelic session.²⁵ “Set” refers to an individual’s mindset going into a session, and “setting” refers to the environment in which the session occurs. Typical elements of each are summarized in Table 3.⁷ Psychiatrists will play a critical role in assessing and preparing the “set” by screening patients appropriately, assessing patient goals, and providing a thorough informed consent procedure. Psychiatrists should also be mindful of the “setting,” providing a comfortable, safe, familiar environment and access to appropriate music and eyeshades, if desired. Due to time restraints, psychiatrists are not likely to be responsible for guiding patients through sessions, and should educate themselves about ethical practices of psychedelic guides,if they are in the position to hire guides.^23,24

CASE CONTINUED

Mr. P is enrolled in the academic medical center study assessing the effect of psilocybin on terminal illness-related anxiety and depression. During a 5-hour, 30-mg psilocybin session, he initially experiences distorted visual cues, with vivid, colorful geometric patterns collapsing into each other. He then loses the concepts and experience of time, space, and his body, as his visual distortions convert to darkness. After what seems like a decade within the darkness, he sees himself lying in a hospital bed with loved ones surrounding him. He watches himself take his last breaths and his family members weep as he dies. As he regains his senses, Mr. P feels that he is being reborn.

In the therapy sessions that follow the psychedelic session, Mr. P reports feeling “finally freed” from the fear, sadness, and anger that he has felt throughout his life. He comes to accept his impending death with gratitude and peace. In his final days, he no longer experiences depression or anxiety. Mr. P’s friends and family members comment that he seems to be the best version of himself in the months that lead up to his death.

Related Resources

• Nutt D. Psychedelic drugs-a new era in psychiatry? Dialogues Clin Neurosci. 2019;21(2):139-147.

• Garcia-Romeu A, Kersgaard B, Addy PH. Clinical applications of hallucinogens: a review. Exp Clin Psychopharmacol. 2016; 24(4):229-268.

Drug Brand Names

Amitriptyline • Amitril, Elavil
Bupropion • Wellbutrin
Fluoxetine • Prozac
Sertraline • Zoloft

Bottom Line

Psychedelics are a class of consciousness-altering agents that have become a potentially promising source of new treatments for psychiatric illness. Although more evidence is needed, compounds such as psilocybin may one day become FDAapproved for conditions such as terminal illness–related depression and anxiety, and substance use disorders. When this occurs, psychiatrists should be responsible for prescribing psychedelics and managing patients who receive treatment.

Mr. P, age 65, has a history of major depressive disorder (MDD), generalized anxiety disorder, and social phobia. Mr. P’s personality is high in neuroticism and he has often responded to new situations with feelings of impending doom. For him, fear, anxious rumination, helplessness, and catastrophizing are familiar mental processes.

When he was in his 30s, Mr. P had a severe major depressive episode with suicidal ideation and sought care from a psychiatrist. He began a treatment program of psychotherapy and concomitant psychopharmacotherapy with consecutive trials of fluoxetine, sertraline, and amitriptyline, each of an adequate dose and duration. With each medication, Mr. P experienced new adverse effects, including nausea, constipation, tremors, and headache. His psychiatrist transitioned him to bupropion, which helped Mr. P most. For the next several decades, Mr. P continued to experience low-grade depressive symptoms with intermittent exacerbation to mild-to-moderate major depressive episodes, but he remained adherent to his medication and continued psychotherapy.

Shortly after his 65th birthday, Mr. P experiences progressively worsening nausea and abdominal pain. Initially, he assumes the symptoms are secondary to anxiety. Taking his psychiatrist’s advice, Mr. P visits his primary care physician. A work-up reveals that Mr. P has advanced pancreatic cancer, and an oncologist estimates Mr. P has 6 months of life remaining.

Following his cancer diagnosis, Mr. P quickly develops symptoms of MDD despite continuing to take bupropion. Within a week he becomes withdrawn and hopeless, and thinks about ending his life “before God does.” His psychiatrist urges Mr. P to contact the local academic medical center because it is conducting a trial of a “new” drug, psilocybin, to treat anxiety and depression in patients with terminal illness.

Beginning in the 1940s, a growing body of scientific evidence suggested that psychedelic compounds such as lysergic acid diethylamide (LSD) could benefit individuals with various psychiatric maladies. Research interest in LSD and substances with similar effects persisted until the late 1960s. In response to the growing counterculture movement in the United States and the efforts of Harvard researchers Timothy Leary and Richard Alpert to popularize psychedelic drug use in the general population, in 1970 President Richard M. Nixon signed the Controlled Substances Act (CSA) into law. The CSA categorized LSD as a Schedule I drug, rendering its manufacture and distribution illegal. Research into the potential therapeutic benefits of LSD was effectively halted.¹ In recent decades, however, there has been a quiet but growing renaissance of scientific interest in the effects of psychedelics on a variety of conditions, including terminal illness–related anxiety and depression, treatment-resistant depression, and substance use disorders (SUDs). One example is psilocybin, which is currently undergoing Phase 2 and 3 clinical trials in North America and Europe for treatment-resistant depression.

As researchers have once again picked up the torch in the pursuit of psychedelic therapeutics, jurisdictions in the United States are also relaxing their stance on these drugs. In 2019 and early 2020, Denver, Oakland, and Santa Cruz became the first 3 cities in the United States to decriminalize the possession of various psychedelic substances.^2-4 With the passage of Measure 109 in November 2020, Oregon became the first state to decriminalize the use of psychedelic mushrooms in therapeutic settings.⁵ The combined forces of increased research and relaxed political concern related to psychedelics might make it possible for the FDA to approve their use for psychiatric conditions. Therefore, it is critical for psychiatrists to understand the psychopharmacology, range of effects, and potential risks and benefits of these agents. In this article, I describe what psychedelics are and how they work, summarize a few research findings about psilocybin, and offer a framework for psychedelic psychiatric practice in the years to come.

What are psychedelics?

Psychiatrist Humphry Osmond first coined the term “psychedelic” in 1957 at a meeting of the New York Academy of Sciences, where he was discussing his research on the effect of LSD on patients at the Weyburn Mental Hospital in Saskatchewan, Canada.⁶ Prior to 1957, LSD had been described as a “psycho­tomimetic” drug because it was believed to induce a state of psychosis similar to that experienced in schizophrenia. But LSD does not generally induce frank auditory hallucinations or clearly defined delusional beliefs. Osmond’s new term—derived from the Greek words psyche, meaning “mind,” and delos, meaning “to show”—referred to the “mind-manifesting” capacities of LSD and related drugs.⁶ Psychedelic drugs can cause an array of changes to an individual’s conscious experience, from relatively mild changes in visual perception to profound derangements in sense of self and reality.

Continue to: Before describing the effects...

Classic psychedelics vs other compounds

Before describing the effects of psychedelic drugs and how they may relate to their therapeutic potential, it is useful to define which compounds are considered “classic psychedelics.”

The classic psychedelics are substances that operate primarily through activation of the serotonin 5-hydroxytryptamine receptor 2A receptor (5-HT2A) (Table 1⁷). Many psychedelic drugs are derived from natural sources, including plants, fungi, and animals. For example, N, N-dimethyltryptamine (DMT), which is one of the most potent psychedelic compounds, is found in various plant species and can be imbibed in a tea known as ayahuasca, most commonly in the context of spiritual ceremonies.

How psychedelics work

Psychedelics can induce a spectrum of effects that are not necessarily dose-dependent. Mild effects of intoxication include altered sensory perception in visual, auditory, proprioceptive, and somatosensory spheres, including synesthesia. Progressively more severe changes include a distorted or eliminated perception or awareness of space, time, body, and self, resulting in derealization and depersonalization. Some of the most extreme alterations of consciousness reported by users include mystical or transcendent experiences of birth, giving birth, death, exchanging bodies with a nonhuman species, and meeting otherworldly beings.¹¹ In terms of neurophysiology, psychedelics cause altered cerebral blood flow and metabolism, increased connectivity between brain regions that do not typically communicate, and a reduction in the activity of a group of cortical structures called the default mode network (DMN).¹²

Continue to: Researchers hypothesize that...

Researchers hypothesize that the disruption of DMN activity may be a key mechanism accounting for psychedelics’ therapeutic effects in mental illness. The DMN is a group of structures that includes the posterior cingulate cortex, the medial prefrontal cortex, the angular gyrus, and other cortical areas that are active when an individual is not engaged in a particular mental task (for example, during mind wandering). It is thought to underlie introspection and to serve as an “orchestrator” of global brain function.¹³ Theoretically, then, by temporarily disrupting the neural circuits responsible for maintaining ingrained, negative thought and behavioral patterns, as observed in patients with depression or SUDs, psychedelics can help patients develop greater emotional and cognitive flexibility and identify new ways to view the world and to solve problems.

Evaluating psychedelics as therapeutic agents

The renaissance of research into psychedelics as therapeutic agents during the last 2 decades has produced some promising preliminary findings. In 2020, the American Psychiatric Association’s Work Group on Biomarkers and Novel Treatments published a review of the best evidence on the topic.¹⁴ Psilocybin is the most studied drug because compared with LSD, it carries less of a stigma and has a shorter duration of action. Psilocybin has been studied as a potential treatment for several psychiatric disorders, including terminal illness–related depression and anxiety, and SUDs.

Griffiths et al.¹⁵ In a double-blind randomized crossover study at Johns Hopkins School of Medicine, Griffiths et al¹⁵ administered a high dose (22 or 30 mg/70 kg) and a very low, placebo-like dose (1 or 3 mg/70 kg) of psilocybin at 2 separate sessions to 51 patients with terminal cancer and associated depressive and anxiety disorders. After 5 weeks, the participants assigned to one condition crossed over to the other condition. High-dose psilocybin had a significant effect on depression and anxiety symptoms within 5 weeks that persisted over 6 months of follow-up. At 6 months, 78% of participants experienced a response in depressive symptoms (≥50% decrease in GRID-Hamilton Depression Rating Scale [HAM-D-17] baseline scores) and 65% remitted (GRID-HAM-D-17 score ≤7). At 6 months, 83% of participants had a response in anxiety symptoms (≥50% decrease in Hamilton Rating Scale for Anxiety [HAM-A] baseline scores) and 57% remitted (HAM-A ≤7).

Johnson et al.^16,17 In an open-label pilot study¹⁶ and ≥12-month follow-up study,¹⁷ Johnson et al administered a moderate (20 mg/70 kg) and high (30 mg/70 kg) dose of psilocybin to 15 participants enrolled in a 15-week smoking session program. The psilocybin sessions were scheduled at Weeks 5 and 7, with an optional psilocybin session at Week 13. The sessions included nondirective support from program staff, but not smoking cessation content. Relying on laboratory-verified exhaled carbon monoxide and urine cotinine measures, researchers found an 80% abstinence rate at 6 months, a 67% abstinence rate at 12 months, and a 75% abstinence rate at 2.5 years.^16,17

Bogenschutz et al¹⁸ conducted a study of 10 patients who met DSM-IV criteria for alcohol dependence and had at least 2 heavy drinking days in the previous 30 days. They found that a 14-session treatment program that included 2 psilocybin-assisted psychotherapy sessions with dosages of 0.4 mg/kg resulted in a significant increase in self-reported alcohol abstinence at 4 weeks that persisted for 36 weeks.¹⁸

Although these studies were small, open-label, and had other methodologic flaws, their pilot work has led to larger-scale projects assessing psilocybin’s therapeutic potential. Psilocybin has also been studied for treatment-resistant depression and obsessive-compulsive disorder. Other clinical trials underway are investigating psilocybin for the treatment of cocaine and opioid use disorder, anorexia nervosa, and depression in Alzheimer’s disease.¹⁴ Although psilocybin is currently the best-studied psychedelic, there is some research demonstrating that LSD can also induce a persistent reduction in anxiety symptoms associated with terminal illness¹⁹ and that ayahuasca causes a rapid reduction in depressive symptoms that persists over 21 days.²⁰

Continue to: The future of psychedelic psychiatry...

The future of psychedelic psychiatry

If psychedelic compounds become approved for the treatment of psychiatric conditions, psychiatrists will likely be responsible for prescribing them and managing patients who receive them.²¹Table 2^11,21-24 summarizes practical considerations for psychiatrists who may someday be prescribing psychedelic drugs. Areas of psychedelic treatment in which psychiatric expertise is necessary include:

• screening for patients at increased risk for a challenging or adverse experience or “bad trip”
• conducting a thorough informed consent process in which the risks are discussed and the patient’s wishes regarding potential situations are elicited
• managing acute medical and psychiatric complications, including agitation and violent behavior
• ensuring the use of trained guides during sessions.

Psychiatrists who are interested in providing psychedelic-assisted therapy should understand the concept of “set and setting,” which was defined by Timothy Leary in the 1960s and is thought to play an important role in determining the types of experiences that arise during a psychedelic session.²⁵ “Set” refers to an individual’s mindset going into a session, and “setting” refers to the environment in which the session occurs. Typical elements of each are summarized in Table 3.⁷ Psychiatrists will play a critical role in assessing and preparing the “set” by screening patients appropriately, assessing patient goals, and providing a thorough informed consent procedure. Psychiatrists should also be mindful of the “setting,” providing a comfortable, safe, familiar environment and access to appropriate music and eyeshades, if desired. Due to time restraints, psychiatrists are not likely to be responsible for guiding patients through sessions, and should educate themselves about ethical practices of psychedelic guides,if they are in the position to hire guides.^23,24

CASE CONTINUED

Mr. P is enrolled in the academic medical center study assessing the effect of psilocybin on terminal illness-related anxiety and depression. During a 5-hour, 30-mg psilocybin session, he initially experiences distorted visual cues, with vivid, colorful geometric patterns collapsing into each other. He then loses the concepts and experience of time, space, and his body, as his visual distortions convert to darkness. After what seems like a decade within the darkness, he sees himself lying in a hospital bed with loved ones surrounding him. He watches himself take his last breaths and his family members weep as he dies. As he regains his senses, Mr. P feels that he is being reborn.

In the therapy sessions that follow the psychedelic session, Mr. P reports feeling “finally freed” from the fear, sadness, and anger that he has felt throughout his life. He comes to accept his impending death with gratitude and peace. In his final days, he no longer experiences depression or anxiety. Mr. P’s friends and family members comment that he seems to be the best version of himself in the months that lead up to his death.

Related Resources

• Nutt D. Psychedelic drugs-a new era in psychiatry? Dialogues Clin Neurosci. 2019;21(2):139-147.

• Garcia-Romeu A, Kersgaard B, Addy PH. Clinical applications of hallucinogens: a review. Exp Clin Psychopharmacol. 2016; 24(4):229-268.

Drug Brand Names

Amitriptyline • Amitril, Elavil
Bupropion • Wellbutrin
Fluoxetine • Prozac
Sertraline • Zoloft

Bottom Line

Psychedelics are a class of consciousness-altering agents that have become a potentially promising source of new treatments for psychiatric illness. Although more evidence is needed, compounds such as psilocybin may one day become FDAapproved for conditions such as terminal illness–related depression and anxiety, and substance use disorders. When this occurs, psychiatrists should be responsible for prescribing psychedelics and managing patients who receive treatment.

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Cannabis is ineffective at alleviating depression in pregnant women undergoing opioid agonist therapy (OAT), new research shows.

RyanKing999/iStock/Getty Images

A study of more than 120 pregnant women undergoing treatment of opioid use disorder (OUD) showed that those who used cannabis to alleviate their depressive symptoms while undergoing OAT continued to have high depression scores at the end of opioid treatment.

In addition, depression scores improved for those who abstained from cannabis use after their first positive screen. Interestingly, cannabis use did not affect patient retention in treatment for OUD, the investigators note.

“To our knowledge, this is the first time looking at the impact of cannabis on the specific population of pregnant women with opioid use disorder, who are very vulnerable to depression,” lead author Abigail Richison, MD, University of Arkansas for Medical Sciences, Little Rock, said in an interview.

The findings were presented at the American Academy of Addiction Psychiatry (AAAP) 31st Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

A safer alternative?

Data from the National Survey on Drug Use and Health show that perinatal cannabis use increased by 62% between 2002 and 2014. Many women try to ameliorate their depression symptoms by using cannabis in the mistaken belief that it will help their depression, the investigators noted.

In addition, many women consider cannabis safer during pregnancy than prescribed medications for improving mood, said Dr. Richison. She said that cannabis does not alleviate depression and may even worsen it.

Dr. Richison noted that at her center, which has a women’s health program that treats pregnant women with OUDs, she was seeing a lot of patients who reported using cannabis to improve their mood.

“However, it didn’t seem like it was really helping, so I started researching about cannabis and depression,” Dr. Richison said.

“I’ve always been interested in this population because they are very vulnerable to legal implications and can be accused of perinatal substance use. I think it is very important to screen for depression as well as cannabis use in this population,” she added.

To shed some light on the impact of cannabis use by pregnant patients with OUD, the investigators conducted a retrospective chart review of 121 pregnant women with OUD who attended outpatient OAT. All were prescribed buprenorphine.

At each visit, Beck Depression Inventory (BDI) scores were obtained and urine drug screens were administered. The primary outcome was BDI score. Other measures included retention, urinary drug screen results, and antidepressant use.

The women were divided into two groups. The first comprised cannabis users, defined as having more than one urine drug screen that was positive for cannabis (n = 35). The other group comprised nonusers, defined as having urine drug screens that were negative for cannabis (n = 86).

Cannabis users were a little younger (mean age, 27 years) than non–cannabis users (mean age, 29.5 years; P = .006). Most of the participants were White (80.2%). Roughly half were on Medicaid, and most of the other participants had private insurance; a small number of women had no insurance.

Results showed that cannabis users had significantly higher BDI scores than non–cannabis users (mean scores, 16 vs. 9.3; P < .001).

Cannabis use continued to be associated with elevated scores for depression when controlling for opioid misuse and antidepressant use. There were no significant differences in retention or lapse to opioid misuse between the two groups.
 

More evidence of risk

Commenting on the findings in an interview, Carla Marienfeld, MD, professor of psychiatry at the University of California, San Diego, said there is a growing body of evidence about risks from cannabis use during pregnancy, “a time where we already know the endocannabinoid system is very active in the developing fetus.”

She noted that the current study’s design makes it hard to know whether marijuana use causes worse depression.

However, “it clearly is not associated with helping to improve mood the way people who are using it believe or hope for,” said Dr. Marienfeld, who was not part of the research.

“The risk for harm in terms of worse mood for the pregnant woman or risks for harm to the developing fetus are being better understood with many new studies,” she added.

Yet as more and more states legalize medical marijuana, cannabis use during pregnancy is only going to rise, experts fear.

Cornel Stanciu, MD, of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., who was asked for comment, noted that public endorsement for potential benefits of the marijuana plant is at an all-time high.

“To date, 33 states and the District of Columbia have responded by legalizing medical marijuana, with 10 states also having legalized recreational use of marijuana. The current practice is said to be ahead of science, as robust research has been hindered by strict regulations – and most epidemiological studies point toward harmful associations,” Dr. Stanciu said in an interview.

“Given the decreased perception of harm by the general public, women are certainly compelled to seek what they perceive as more natural self-management remedies,” he said.
 

A harmful habit

Dr. Stanciu cited a recent study conducted in Colorado in which researchers contacted cannabis dispensaries, identified themselves as being pregnant, and asked for guidance in managing pregnancy-related symptoms.

Almost 70% of dispensaries recommended products to treat symptoms, particularly in the vulnerable first trimester; 36% of them also provided reassurance of the safety profile. Very few encouraged a discussion with the physician.

“Consumption of cannabis during pregnancy results in cannabinoid placental crossing and accumulation in the fetal brain, as well as other organs, where it interferes with neurodevelopment and the endocannabinoid system,” he said.

In addition, retrospective studies have shown an association between prenatal cannabis ingestion and anemia in the mothers, low birth weight, greater risk for preterm and stillbirths, and increased need for neonatal ICU admissions.

“Children born to mothers who used cannabis during pregnancy have higher rates of impulsivity, delinquency, learning and memory impairment, as well as executive function deficits. There is also an increased association with proneness to psychosis during middle childhood,” Dr. Stanciu said.

When used during pregnancy, cannabis has been associated with increased anxiety in mothers, as well as increased risk for depressive disorders, incidence of suicidal ideations and behavior, and symptoms of mania and psychosis among those with bipolar and schizophrenia spectrum conditions. Cannabis has also been linked to coingestion of other substances and with alcohol use.

“So cannabis can pose harm, especially when used by those with affective disorders,” Dr. Stanciu said.

The study was funded by the National Institute on Drug Abuse. Dr. Richison, Dr. Marienfeld, and Dr. Stanciu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

A version of this article first appeared on Medscape.com.

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

A version of this article first appeared on Medscape.com.

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

A version of this article first appeared on Medscape.com.