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Severe Mental Disorders Highly Prevalent in Jails, Prisons
BOSTON – U.S. correctional institutions are estimated to be housing 1 million men and women with serious mental illnesses such as schizophrenia or a major affective disorder, investigators reported at the annual meeting of the American Academy of Psychiatry and the Law.
The estimated prevalence of serious mental disorders among U.S. inmates ranges from 7% to 16%. Men with mental illness are four times more likely to be incarcerated than the general population, and women with mental illness have an eightfold higher risk, reported Georgia Stathopoulou, Ph.D., and her colleagues from Massachusetts General Hospital and Harvard Medical School, both in Boston.
"The prevalence of serious mental health issues is higher among incarcerated individuals than in the general population, and is associated with specific sociodemographic characteristics like male gender, younger age, and non-white race. Severe psychopathology is also associated with higher recidivism and more serious criminal offenses," wrote Dr. Stathopoulou and colleagues Dr. Fabian Saleh and Kristen Czarnecki in a poster presentation.
The investigators reviewed the medical literature and U.S. Department of Justice statistics to get a handle on the size of the problem.
They found that about 804,000 people with severe mental disorders are jailed annually, and that 72% of both men and women with serious mental illness who are in jail had a co-occurring substance use disorder.
The high rates of substance use and abuse is one of the primary factors contributing to the high incarceration rate of the mentally ill, they said. Other factors, they said, are:
"The prevalence of serious mental health issues is higher among incarcerated individuals than in the general population."
• Insufficient community resources.
• A national drug policy that emphasizes interdiction over treatment.
• Delays in release from prisons and jails to the community.
• Insufficient inmate access to evidence-based mental health therapies.
• Insufficient planning for reentry of mental health inmates into the community.
Jail inmates with mental health disorders are twice as likely as inmates without mental illness to have been homeless in the year before their arrest (13% vs. 6%), 3 times more likely to report a history of sexual or physical abuse (24% vs. 8%), and twice as likely to have lived in a foster home or institution when they were growing up, the authors found.
Specific criminal actions associated with mental disorder diagnoses include higher rates of assault among inmates with bipolar disorder, and higher assault, homicide, and drug possession rates among those with schizophrenia or nonschizophrenic psychosis.
High Recidivism Rates
The investigators cited a retrospective study of more than 79,000 Texas inmates, which found that inmates with bipolar disorder were more than 3 times more likely than inmates without psychiatric disorders to be incarcerated 4 or more times during a 6-year period (Am. J. Psychiatry 2009;166:103-9).
Inmates with major depressive disorder, schizophrenia, and nonschizophrenic psychotic disorders also were significantly more likely to be imprisoned repeatedly, compared with the general prison population.
In all, 89% of the state public and private adult correctional facilities provide some type of mental health services to inmates. Of this group, 51% provide around-the-clock services, 71% offer therapy or counseling from trained mental health professional, and 73% dispense psychotropic drugs.
"We need new treatments, and these treatments have to be evidence based. These treatments have to address both public safety and the clinical needs of inmates," Dr. Stathopoulou said in an interview.
The authors did not disclose a funding source for the study. Dr. Stathopoulou reported that she had no relevant conflicts of interest.
BOSTON – U.S. correctional institutions are estimated to be housing 1 million men and women with serious mental illnesses such as schizophrenia or a major affective disorder, investigators reported at the annual meeting of the American Academy of Psychiatry and the Law.
The estimated prevalence of serious mental disorders among U.S. inmates ranges from 7% to 16%. Men with mental illness are four times more likely to be incarcerated than the general population, and women with mental illness have an eightfold higher risk, reported Georgia Stathopoulou, Ph.D., and her colleagues from Massachusetts General Hospital and Harvard Medical School, both in Boston.
"The prevalence of serious mental health issues is higher among incarcerated individuals than in the general population, and is associated with specific sociodemographic characteristics like male gender, younger age, and non-white race. Severe psychopathology is also associated with higher recidivism and more serious criminal offenses," wrote Dr. Stathopoulou and colleagues Dr. Fabian Saleh and Kristen Czarnecki in a poster presentation.
The investigators reviewed the medical literature and U.S. Department of Justice statistics to get a handle on the size of the problem.
They found that about 804,000 people with severe mental disorders are jailed annually, and that 72% of both men and women with serious mental illness who are in jail had a co-occurring substance use disorder.
The high rates of substance use and abuse is one of the primary factors contributing to the high incarceration rate of the mentally ill, they said. Other factors, they said, are:
"The prevalence of serious mental health issues is higher among incarcerated individuals than in the general population."
• Insufficient community resources.
• A national drug policy that emphasizes interdiction over treatment.
• Delays in release from prisons and jails to the community.
• Insufficient inmate access to evidence-based mental health therapies.
• Insufficient planning for reentry of mental health inmates into the community.
Jail inmates with mental health disorders are twice as likely as inmates without mental illness to have been homeless in the year before their arrest (13% vs. 6%), 3 times more likely to report a history of sexual or physical abuse (24% vs. 8%), and twice as likely to have lived in a foster home or institution when they were growing up, the authors found.
Specific criminal actions associated with mental disorder diagnoses include higher rates of assault among inmates with bipolar disorder, and higher assault, homicide, and drug possession rates among those with schizophrenia or nonschizophrenic psychosis.
High Recidivism Rates
The investigators cited a retrospective study of more than 79,000 Texas inmates, which found that inmates with bipolar disorder were more than 3 times more likely than inmates without psychiatric disorders to be incarcerated 4 or more times during a 6-year period (Am. J. Psychiatry 2009;166:103-9).
Inmates with major depressive disorder, schizophrenia, and nonschizophrenic psychotic disorders also were significantly more likely to be imprisoned repeatedly, compared with the general prison population.
In all, 89% of the state public and private adult correctional facilities provide some type of mental health services to inmates. Of this group, 51% provide around-the-clock services, 71% offer therapy or counseling from trained mental health professional, and 73% dispense psychotropic drugs.
"We need new treatments, and these treatments have to be evidence based. These treatments have to address both public safety and the clinical needs of inmates," Dr. Stathopoulou said in an interview.
The authors did not disclose a funding source for the study. Dr. Stathopoulou reported that she had no relevant conflicts of interest.
BOSTON – U.S. correctional institutions are estimated to be housing 1 million men and women with serious mental illnesses such as schizophrenia or a major affective disorder, investigators reported at the annual meeting of the American Academy of Psychiatry and the Law.
The estimated prevalence of serious mental disorders among U.S. inmates ranges from 7% to 16%. Men with mental illness are four times more likely to be incarcerated than the general population, and women with mental illness have an eightfold higher risk, reported Georgia Stathopoulou, Ph.D., and her colleagues from Massachusetts General Hospital and Harvard Medical School, both in Boston.
"The prevalence of serious mental health issues is higher among incarcerated individuals than in the general population, and is associated with specific sociodemographic characteristics like male gender, younger age, and non-white race. Severe psychopathology is also associated with higher recidivism and more serious criminal offenses," wrote Dr. Stathopoulou and colleagues Dr. Fabian Saleh and Kristen Czarnecki in a poster presentation.
The investigators reviewed the medical literature and U.S. Department of Justice statistics to get a handle on the size of the problem.
They found that about 804,000 people with severe mental disorders are jailed annually, and that 72% of both men and women with serious mental illness who are in jail had a co-occurring substance use disorder.
The high rates of substance use and abuse is one of the primary factors contributing to the high incarceration rate of the mentally ill, they said. Other factors, they said, are:
"The prevalence of serious mental health issues is higher among incarcerated individuals than in the general population."
• Insufficient community resources.
• A national drug policy that emphasizes interdiction over treatment.
• Delays in release from prisons and jails to the community.
• Insufficient inmate access to evidence-based mental health therapies.
• Insufficient planning for reentry of mental health inmates into the community.
Jail inmates with mental health disorders are twice as likely as inmates without mental illness to have been homeless in the year before their arrest (13% vs. 6%), 3 times more likely to report a history of sexual or physical abuse (24% vs. 8%), and twice as likely to have lived in a foster home or institution when they were growing up, the authors found.
Specific criminal actions associated with mental disorder diagnoses include higher rates of assault among inmates with bipolar disorder, and higher assault, homicide, and drug possession rates among those with schizophrenia or nonschizophrenic psychosis.
High Recidivism Rates
The investigators cited a retrospective study of more than 79,000 Texas inmates, which found that inmates with bipolar disorder were more than 3 times more likely than inmates without psychiatric disorders to be incarcerated 4 or more times during a 6-year period (Am. J. Psychiatry 2009;166:103-9).
Inmates with major depressive disorder, schizophrenia, and nonschizophrenic psychotic disorders also were significantly more likely to be imprisoned repeatedly, compared with the general prison population.
In all, 89% of the state public and private adult correctional facilities provide some type of mental health services to inmates. Of this group, 51% provide around-the-clock services, 71% offer therapy or counseling from trained mental health professional, and 73% dispense psychotropic drugs.
"We need new treatments, and these treatments have to be evidence based. These treatments have to address both public safety and the clinical needs of inmates," Dr. Stathopoulou said in an interview.
The authors did not disclose a funding source for the study. Dr. Stathopoulou reported that she had no relevant conflicts of interest.
FROM THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW
Major Finding: The estimated prevalence of serious mental disorders among U.S. inmates ranges from 7% to 16%.
Data Source: Review of medical literature and Department of Justice statistics.
Disclosures: The authors did not disclose a funding source for the study. Dr. Stathopoulou reported that she had no relevant conflicts of interest.
Caffeine Linked to Psychosis in Case Series
BOSTON – Most people just get a mild buzz from their morning coffee, but an unfortunate few have reactions to caffeine ranging from severe agitation to paranoid delusions and psychosis, forensic psychiatrists reported in a poster presented at the annual meeting of the American Academy of Psychiatry in the Law.
Caffeine is known to act as an antagonist of the adenosine A2a receptor, thereby causing an increase in dopaminergic neurotransmission, especially in areas of the brain rich in D2 receptors. "This mechanism may cause or exacerbate psychotic symptoms, and is also triggered by modulation of transmission in the mesolimbic dopaminergic pathways," wrote Dr. Christopher M. Davidson of the University of South Dakota Sanford School of Medicine, Sioux Falls, and his associates.
Caffeine is metabolized by the cytochrome P450 1A2 enzyme. Polymorphisms in the enzyme might affect how individuals metabolize and respond to caffeine, the authors said.
They reported on a forensic case and two corrections cases of caffeine-induced mental and behavioral problems.
In the forensics case, a 24-year old man with no history of mental illness assaulted an emergency room nurse after he had driven all night and ingested the caffeine equivalent of about three cups of coffee, said coauthor Dr. James B. Reynolds of the Northwest Missouri Psychiatric Rehabilitation Center, St. Joseph, in an interview.
The patient had been brought to the emergency department by police whom he had sought out when he began experiencing confusion and paranoia. At one point, without apparent provocation, he jumped out of bed, grabbed the nurse, and shouted: "Why do you do that to me, why do you do that to me?" and cut her neck with a box cutter in his possession.
He was charged with first-degree assault, but was found to have no apparent motive for the assault, no criminal or mental health history, and no evidence of drug or alcohol abuse. He did, however, have a box of caffeine pills in his possession, leading to the conclusion that he was likely suffering from pathologic intoxication.
Dr. Reynolds said that if intoxication occurs because of unforeseeable circumstances, it might qualify as a valid defense against a criminal charge.
Given the circumstances, the prosecutor agreed with the defense, and the man was found not guilty by reason of insanity.
"He came into my hospital, and for nearly 3 years this man was under our observation, and never had one symptom of mental illness and no repeat episode," Dr. Reynolds said.
In the first of the two corrections cases, a 22-year-old man who had been diagnosed with schizophrenia of the catatonic type was living in a section for mentally ill prisoners. He developed new symptoms of activation, irritability, confrontation, restlessness, and high energy with little need for sleep. The episodes occurred at intervals of 1-2 weeks and lasted for 1-3 days.
The mental health staff suspected he had rapid-cycling bipolar-type schizoaffective disorder, and tried treating him with higher doses of olanzapine, augmented with fluphenazine, aripiprazole, and valproic acid, none of which seemed to work.
Through careful observation and documentation, staff noticed that the episodes corresponded to the prisoner’s visits to the commissary, where he bought caffeinated beverages. After he was forbidden to buy coffee or tea, the patient’s maniclike episodes vanished.
In the second case, prison staff saw that a 24-year-old man who had been diagnosed with schizophrenia, undifferentiated type, became agitated and spent most of the night pacing and yelling after he had visited the unit commissary.
"In the months following careful monitoring and restriction of caffeine use in the patient’s housing unit, he had such significant resolution of his symptoms that his doses of trifluophenazine and benzotropine were halved, and he was able to transition to the general population," the authors wrote.
They noted that caffeine is not necessary for the health and functioning of patients in correctional settings, and recommended that institutions either monitor and limit caffeine use, or eliminate it in some correctional settings. They also called for further investigation of highly variable responses to caffeine.
The authors did not disclose a funding source. Dr. Davidson, Dr. Reynolds, and their coauthors reported that they had no relevant financial disclosures.
BOSTON – Most people just get a mild buzz from their morning coffee, but an unfortunate few have reactions to caffeine ranging from severe agitation to paranoid delusions and psychosis, forensic psychiatrists reported in a poster presented at the annual meeting of the American Academy of Psychiatry in the Law.
Caffeine is known to act as an antagonist of the adenosine A2a receptor, thereby causing an increase in dopaminergic neurotransmission, especially in areas of the brain rich in D2 receptors. "This mechanism may cause or exacerbate psychotic symptoms, and is also triggered by modulation of transmission in the mesolimbic dopaminergic pathways," wrote Dr. Christopher M. Davidson of the University of South Dakota Sanford School of Medicine, Sioux Falls, and his associates.
Caffeine is metabolized by the cytochrome P450 1A2 enzyme. Polymorphisms in the enzyme might affect how individuals metabolize and respond to caffeine, the authors said.
They reported on a forensic case and two corrections cases of caffeine-induced mental and behavioral problems.
In the forensics case, a 24-year old man with no history of mental illness assaulted an emergency room nurse after he had driven all night and ingested the caffeine equivalent of about three cups of coffee, said coauthor Dr. James B. Reynolds of the Northwest Missouri Psychiatric Rehabilitation Center, St. Joseph, in an interview.
The patient had been brought to the emergency department by police whom he had sought out when he began experiencing confusion and paranoia. At one point, without apparent provocation, he jumped out of bed, grabbed the nurse, and shouted: "Why do you do that to me, why do you do that to me?" and cut her neck with a box cutter in his possession.
He was charged with first-degree assault, but was found to have no apparent motive for the assault, no criminal or mental health history, and no evidence of drug or alcohol abuse. He did, however, have a box of caffeine pills in his possession, leading to the conclusion that he was likely suffering from pathologic intoxication.
Dr. Reynolds said that if intoxication occurs because of unforeseeable circumstances, it might qualify as a valid defense against a criminal charge.
Given the circumstances, the prosecutor agreed with the defense, and the man was found not guilty by reason of insanity.
"He came into my hospital, and for nearly 3 years this man was under our observation, and never had one symptom of mental illness and no repeat episode," Dr. Reynolds said.
In the first of the two corrections cases, a 22-year-old man who had been diagnosed with schizophrenia of the catatonic type was living in a section for mentally ill prisoners. He developed new symptoms of activation, irritability, confrontation, restlessness, and high energy with little need for sleep. The episodes occurred at intervals of 1-2 weeks and lasted for 1-3 days.
The mental health staff suspected he had rapid-cycling bipolar-type schizoaffective disorder, and tried treating him with higher doses of olanzapine, augmented with fluphenazine, aripiprazole, and valproic acid, none of which seemed to work.
Through careful observation and documentation, staff noticed that the episodes corresponded to the prisoner’s visits to the commissary, where he bought caffeinated beverages. After he was forbidden to buy coffee or tea, the patient’s maniclike episodes vanished.
In the second case, prison staff saw that a 24-year-old man who had been diagnosed with schizophrenia, undifferentiated type, became agitated and spent most of the night pacing and yelling after he had visited the unit commissary.
"In the months following careful monitoring and restriction of caffeine use in the patient’s housing unit, he had such significant resolution of his symptoms that his doses of trifluophenazine and benzotropine were halved, and he was able to transition to the general population," the authors wrote.
They noted that caffeine is not necessary for the health and functioning of patients in correctional settings, and recommended that institutions either monitor and limit caffeine use, or eliminate it in some correctional settings. They also called for further investigation of highly variable responses to caffeine.
The authors did not disclose a funding source. Dr. Davidson, Dr. Reynolds, and their coauthors reported that they had no relevant financial disclosures.
BOSTON – Most people just get a mild buzz from their morning coffee, but an unfortunate few have reactions to caffeine ranging from severe agitation to paranoid delusions and psychosis, forensic psychiatrists reported in a poster presented at the annual meeting of the American Academy of Psychiatry in the Law.
Caffeine is known to act as an antagonist of the adenosine A2a receptor, thereby causing an increase in dopaminergic neurotransmission, especially in areas of the brain rich in D2 receptors. "This mechanism may cause or exacerbate psychotic symptoms, and is also triggered by modulation of transmission in the mesolimbic dopaminergic pathways," wrote Dr. Christopher M. Davidson of the University of South Dakota Sanford School of Medicine, Sioux Falls, and his associates.
Caffeine is metabolized by the cytochrome P450 1A2 enzyme. Polymorphisms in the enzyme might affect how individuals metabolize and respond to caffeine, the authors said.
They reported on a forensic case and two corrections cases of caffeine-induced mental and behavioral problems.
In the forensics case, a 24-year old man with no history of mental illness assaulted an emergency room nurse after he had driven all night and ingested the caffeine equivalent of about three cups of coffee, said coauthor Dr. James B. Reynolds of the Northwest Missouri Psychiatric Rehabilitation Center, St. Joseph, in an interview.
The patient had been brought to the emergency department by police whom he had sought out when he began experiencing confusion and paranoia. At one point, without apparent provocation, he jumped out of bed, grabbed the nurse, and shouted: "Why do you do that to me, why do you do that to me?" and cut her neck with a box cutter in his possession.
He was charged with first-degree assault, but was found to have no apparent motive for the assault, no criminal or mental health history, and no evidence of drug or alcohol abuse. He did, however, have a box of caffeine pills in his possession, leading to the conclusion that he was likely suffering from pathologic intoxication.
Dr. Reynolds said that if intoxication occurs because of unforeseeable circumstances, it might qualify as a valid defense against a criminal charge.
Given the circumstances, the prosecutor agreed with the defense, and the man was found not guilty by reason of insanity.
"He came into my hospital, and for nearly 3 years this man was under our observation, and never had one symptom of mental illness and no repeat episode," Dr. Reynolds said.
In the first of the two corrections cases, a 22-year-old man who had been diagnosed with schizophrenia of the catatonic type was living in a section for mentally ill prisoners. He developed new symptoms of activation, irritability, confrontation, restlessness, and high energy with little need for sleep. The episodes occurred at intervals of 1-2 weeks and lasted for 1-3 days.
The mental health staff suspected he had rapid-cycling bipolar-type schizoaffective disorder, and tried treating him with higher doses of olanzapine, augmented with fluphenazine, aripiprazole, and valproic acid, none of which seemed to work.
Through careful observation and documentation, staff noticed that the episodes corresponded to the prisoner’s visits to the commissary, where he bought caffeinated beverages. After he was forbidden to buy coffee or tea, the patient’s maniclike episodes vanished.
In the second case, prison staff saw that a 24-year-old man who had been diagnosed with schizophrenia, undifferentiated type, became agitated and spent most of the night pacing and yelling after he had visited the unit commissary.
"In the months following careful monitoring and restriction of caffeine use in the patient’s housing unit, he had such significant resolution of his symptoms that his doses of trifluophenazine and benzotropine were halved, and he was able to transition to the general population," the authors wrote.
They noted that caffeine is not necessary for the health and functioning of patients in correctional settings, and recommended that institutions either monitor and limit caffeine use, or eliminate it in some correctional settings. They also called for further investigation of highly variable responses to caffeine.
The authors did not disclose a funding source. Dr. Davidson, Dr. Reynolds, and their coauthors reported that they had no relevant financial disclosures.
FROM THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW
Major Finding: Caffeine-induced psychosis may lead to misdiagnosis, unnecessary treatment, or incarceration of susceptible individuals.
Data Source: Case series of patients in correctional and forensic settings.
Disclosures: The authors did not disclose a funding source. Dr. Davidson, Dr. Reynolds, and their coauthors reported that they had no relevant financial disclosures.
Topiramate Plus Quetiapine Cut Cannabis Use in Bipolar Teens
TORONTO – Topiramate in combination with quetiapine was well tolerated in adolescents who had bipolar disorder and reported frequent cannabis use, based on a 75-patient study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Concurrent substance use is a barrier to treating adolescents with bipolar disorder, said Dr. Melissa DelBello of the University of Cincinnati. Topiramate is approved by the Food and Drug Administration as an antiepileptic drug for children as young as age 2 years. Topiramate has been shown to reduce drug cravings, but is not approved for that indication, she added.
©ron hilton/iStockphoto.com
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The researchers recruited adolescents, aged 12-21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week for the 28 days before entering the study. In a previous study, Dr. DelBello and her colleagues found that topiramate was effective for reducing mania symptoms in adolescents (J. Am. Acad. Child Adolesc. Psychiatry 2005; 44:539-47).
The 75 teens were randomized to a maximum of 800 mg of quetiapine and placebo or to quetiapine and a minimum dose of 75 mg of topiramate twice daily that was increased gradually to 150 mg twice daily by day 21 of treatment.
At baseline, the average number of joints smoked per week was 14 in the quetiapine and placebo group and 11 in the quetiapine and topiramate group.
After 16 weeks of treatment, the average weekly use dropped to four joints in the quetiapine and placebo group and to 0.4 joints in the quetiapine and topiramate group. The difference was statistically significant.
On average, teens in the quetiapine and topiramate group used cannabis 1 day per week, and teens in the quetiapine and placebo group used cannabis 2 days per week, Dr. DelBello said.
Over the 16-week study, scores on the YMRS improved significantly from baseline, with an average drop of –14 with quetiapine and topiramate and –16 with quetiapine and placebo. Scores on the Childhood Rating Depression Scale-Revised (CRDS-R) also improved significantly from baseline to 16 weeks in both groups.
The presence of conduct disorder and ADHD were significant predictors of reduction in cannabis use while taking topiramate, said Dr. DelBello. Teens given topiramate showed significant improvement in general scores on the Marijuana Craving Questionnaire, compared with teens given placebo.
The groups did not differ in laboratory measures or vital signs, but excitement and pallor occurred in 26% of the topiramate group and in 16% of the placebo group.
Eleven serious events occurred during the study; five occurred in the topiramate group (two cases of suicidal ideation with intent and three cases of mania) and six occurred in the placebo group (four cases of mania, one suicide attempt, and one pregnancy).
The study was limited by a lack of data on cognition, Dr. DelBello noted. The neurobiological effects of topiramate and its effects when combined with other medications and used in different mood states need further study.
Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.
TORONTO – Topiramate in combination with quetiapine was well tolerated in adolescents who had bipolar disorder and reported frequent cannabis use, based on a 75-patient study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Concurrent substance use is a barrier to treating adolescents with bipolar disorder, said Dr. Melissa DelBello of the University of Cincinnati. Topiramate is approved by the Food and Drug Administration as an antiepileptic drug for children as young as age 2 years. Topiramate has been shown to reduce drug cravings, but is not approved for that indication, she added.
©ron hilton/iStockphoto.com
|
The researchers recruited adolescents, aged 12-21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week for the 28 days before entering the study. In a previous study, Dr. DelBello and her colleagues found that topiramate was effective for reducing mania symptoms in adolescents (J. Am. Acad. Child Adolesc. Psychiatry 2005; 44:539-47).
The 75 teens were randomized to a maximum of 800 mg of quetiapine and placebo or to quetiapine and a minimum dose of 75 mg of topiramate twice daily that was increased gradually to 150 mg twice daily by day 21 of treatment.
At baseline, the average number of joints smoked per week was 14 in the quetiapine and placebo group and 11 in the quetiapine and topiramate group.
After 16 weeks of treatment, the average weekly use dropped to four joints in the quetiapine and placebo group and to 0.4 joints in the quetiapine and topiramate group. The difference was statistically significant.
On average, teens in the quetiapine and topiramate group used cannabis 1 day per week, and teens in the quetiapine and placebo group used cannabis 2 days per week, Dr. DelBello said.
Over the 16-week study, scores on the YMRS improved significantly from baseline, with an average drop of –14 with quetiapine and topiramate and –16 with quetiapine and placebo. Scores on the Childhood Rating Depression Scale-Revised (CRDS-R) also improved significantly from baseline to 16 weeks in both groups.
The presence of conduct disorder and ADHD were significant predictors of reduction in cannabis use while taking topiramate, said Dr. DelBello. Teens given topiramate showed significant improvement in general scores on the Marijuana Craving Questionnaire, compared with teens given placebo.
The groups did not differ in laboratory measures or vital signs, but excitement and pallor occurred in 26% of the topiramate group and in 16% of the placebo group.
Eleven serious events occurred during the study; five occurred in the topiramate group (two cases of suicidal ideation with intent and three cases of mania) and six occurred in the placebo group (four cases of mania, one suicide attempt, and one pregnancy).
The study was limited by a lack of data on cognition, Dr. DelBello noted. The neurobiological effects of topiramate and its effects when combined with other medications and used in different mood states need further study.
Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.
TORONTO – Topiramate in combination with quetiapine was well tolerated in adolescents who had bipolar disorder and reported frequent cannabis use, based on a 75-patient study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.
Concurrent substance use is a barrier to treating adolescents with bipolar disorder, said Dr. Melissa DelBello of the University of Cincinnati. Topiramate is approved by the Food and Drug Administration as an antiepileptic drug for children as young as age 2 years. Topiramate has been shown to reduce drug cravings, but is not approved for that indication, she added.
©ron hilton/iStockphoto.com
|
The researchers recruited adolescents, aged 12-21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week for the 28 days before entering the study. In a previous study, Dr. DelBello and her colleagues found that topiramate was effective for reducing mania symptoms in adolescents (J. Am. Acad. Child Adolesc. Psychiatry 2005; 44:539-47).
The 75 teens were randomized to a maximum of 800 mg of quetiapine and placebo or to quetiapine and a minimum dose of 75 mg of topiramate twice daily that was increased gradually to 150 mg twice daily by day 21 of treatment.
At baseline, the average number of joints smoked per week was 14 in the quetiapine and placebo group and 11 in the quetiapine and topiramate group.
After 16 weeks of treatment, the average weekly use dropped to four joints in the quetiapine and placebo group and to 0.4 joints in the quetiapine and topiramate group. The difference was statistically significant.
On average, teens in the quetiapine and topiramate group used cannabis 1 day per week, and teens in the quetiapine and placebo group used cannabis 2 days per week, Dr. DelBello said.
Over the 16-week study, scores on the YMRS improved significantly from baseline, with an average drop of –14 with quetiapine and topiramate and –16 with quetiapine and placebo. Scores on the Childhood Rating Depression Scale-Revised (CRDS-R) also improved significantly from baseline to 16 weeks in both groups.
The presence of conduct disorder and ADHD were significant predictors of reduction in cannabis use while taking topiramate, said Dr. DelBello. Teens given topiramate showed significant improvement in general scores on the Marijuana Craving Questionnaire, compared with teens given placebo.
The groups did not differ in laboratory measures or vital signs, but excitement and pallor occurred in 26% of the topiramate group and in 16% of the placebo group.
Eleven serious events occurred during the study; five occurred in the topiramate group (two cases of suicidal ideation with intent and three cases of mania) and six occurred in the placebo group (four cases of mania, one suicide attempt, and one pregnancy).
The study was limited by a lack of data on cognition, Dr. DelBello noted. The neurobiological effects of topiramate and its effects when combined with other medications and used in different mood states need further study.
Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.
FROM THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
Major Finding: After 16 weeks of treatment, the average weekly use of cannabis dropped from 14 to 4 joints in the quetiapine and placebo group and from 11 to 0.4 joints in the quetiapine and topiramate group.
Data Source: 75 patients, aged 12 to 21 years, who met criteria for bipolar disorder, had a Young Mania Rating Scale (YMRS) score of at least 20, and were using cannabis an average of at least twice a week during the 28 days before entering the study.
Disclosures: Dr. DelBello has received research support and/or served as a consultant, advisory board member, or speakers’ bureau member for multiple companies including Schering-Plough, Merck, Bristol-Myers Squibb Somerset, Lilly, and Pfizer.
Valproate-induced hair loss: What to tell patients
Ms. B, age 29, has bipolar disorder that is stabilized by valproate, 1,250 mg/d. After 1 month of treatment, she shows scalp hair loss. She takes no other medications and is distressed because she had never experienced such copious hair loss. Ms. B’s blood valproate level is at a therapeutic level. She wants to know if the hair loss will be permanent and what she can do to stop it.
Up to 28% of patients who take valproate suffer temporary alopecia.1,2 In most cases, hair loss is associated with long-term valproate pharmacotherapy. Hair loss appears to be dose-related2 and may be more common in women than in men. Usually patients will report gradual but steady hair loss, commonly beginning 2 to 6 months after initiating treatment.3 Complete hair loss is rare and new hair growth typically begins approximately 2 to 3 months after alopecia onset.
Valproate can cause telogen effluvium, a non-scarring form of alopecia that occurs by precipitating the follicles into a premature rest phase. Other medications that may cause this type of hair loss include desipramine, imipramine, selective serotonin reuptake inhibitors, dopaminergics, anticoagulants, beta blockers, angiotensin-converting enzyme inhibitors, and cimetidine, as well as withdrawal from minoxidil, oral contraceptives, sulfasalazine, and antithyroid medicines.3
Advising patients
In addition to reducing a patient’s valproate dosage when clinically feasible, you can suggest pharmacologic and lifestyle changes to help patients minimize hair loss:
1. Recommend a biotin supplement. Valproate can cause biotin deficiency and may lead to low serum and liver tissue biotinidase enzyme4; a major clinical manifestation of biotin deficiency is alopecia.
2. Tell patients to avoid taking valproate during meals to prevent its chelating effect on food. The chelating effect of valproate makes metals that facilitate hair growth, such as zinc and selenium, unavailable for absorption.5
3. Recommend zinc and selenium supplements, which can help stop further hair loss and regenerate hair.5
4. Suggest practical advice for hair care, including using soft brushes and mild shampoos and avoiding dyes, heated curlers, and hair dryers.
5. Consider minoxidil therapy. However, this is an expensive option and there are no cases documenting its use for alopecia caused by mood stabilizers.
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Castro-Gago M, Gómez-Lado C, Eirís-Puñal J, et al. Serum biotinidase activity in children treated with valproic acid and carbamazepine. J Child Neurol. 2010;25(1):32-35.
2. Patrizi A, Savoia F, Negosanti F, et al. Telogen effluvium caused by magnesium valproate and lamotrigine. Acta Derm Venereol. 2005;85(1):77-78.
3. Mercke Y, Sheng H, Khan T, et al. Hair loss in psychopharmacology. Ann Clin Psychiatry. 2000;12(1):35-42.
4. Yilmaz Y, Tasdemir HA, Paksu MS. The influence of valproic acid treatment on hair and serum zinc levels and serum biotinidase activity. Eur J Paediatr Neurol. 2009;13(5):439-443.
4. Fatemi SH, Calabrese JR. Treatment of valproate-induced alopecia. Ann Pharmacother. 1995;29(12):1302.-
Ms. B, age 29, has bipolar disorder that is stabilized by valproate, 1,250 mg/d. After 1 month of treatment, she shows scalp hair loss. She takes no other medications and is distressed because she had never experienced such copious hair loss. Ms. B’s blood valproate level is at a therapeutic level. She wants to know if the hair loss will be permanent and what she can do to stop it.
Up to 28% of patients who take valproate suffer temporary alopecia.1,2 In most cases, hair loss is associated with long-term valproate pharmacotherapy. Hair loss appears to be dose-related2 and may be more common in women than in men. Usually patients will report gradual but steady hair loss, commonly beginning 2 to 6 months after initiating treatment.3 Complete hair loss is rare and new hair growth typically begins approximately 2 to 3 months after alopecia onset.
Valproate can cause telogen effluvium, a non-scarring form of alopecia that occurs by precipitating the follicles into a premature rest phase. Other medications that may cause this type of hair loss include desipramine, imipramine, selective serotonin reuptake inhibitors, dopaminergics, anticoagulants, beta blockers, angiotensin-converting enzyme inhibitors, and cimetidine, as well as withdrawal from minoxidil, oral contraceptives, sulfasalazine, and antithyroid medicines.3
Advising patients
In addition to reducing a patient’s valproate dosage when clinically feasible, you can suggest pharmacologic and lifestyle changes to help patients minimize hair loss:
1. Recommend a biotin supplement. Valproate can cause biotin deficiency and may lead to low serum and liver tissue biotinidase enzyme4; a major clinical manifestation of biotin deficiency is alopecia.
2. Tell patients to avoid taking valproate during meals to prevent its chelating effect on food. The chelating effect of valproate makes metals that facilitate hair growth, such as zinc and selenium, unavailable for absorption.5
3. Recommend zinc and selenium supplements, which can help stop further hair loss and regenerate hair.5
4. Suggest practical advice for hair care, including using soft brushes and mild shampoos and avoiding dyes, heated curlers, and hair dryers.
5. Consider minoxidil therapy. However, this is an expensive option and there are no cases documenting its use for alopecia caused by mood stabilizers.
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Ms. B, age 29, has bipolar disorder that is stabilized by valproate, 1,250 mg/d. After 1 month of treatment, she shows scalp hair loss. She takes no other medications and is distressed because she had never experienced such copious hair loss. Ms. B’s blood valproate level is at a therapeutic level. She wants to know if the hair loss will be permanent and what she can do to stop it.
Up to 28% of patients who take valproate suffer temporary alopecia.1,2 In most cases, hair loss is associated with long-term valproate pharmacotherapy. Hair loss appears to be dose-related2 and may be more common in women than in men. Usually patients will report gradual but steady hair loss, commonly beginning 2 to 6 months after initiating treatment.3 Complete hair loss is rare and new hair growth typically begins approximately 2 to 3 months after alopecia onset.
Valproate can cause telogen effluvium, a non-scarring form of alopecia that occurs by precipitating the follicles into a premature rest phase. Other medications that may cause this type of hair loss include desipramine, imipramine, selective serotonin reuptake inhibitors, dopaminergics, anticoagulants, beta blockers, angiotensin-converting enzyme inhibitors, and cimetidine, as well as withdrawal from minoxidil, oral contraceptives, sulfasalazine, and antithyroid medicines.3
Advising patients
In addition to reducing a patient’s valproate dosage when clinically feasible, you can suggest pharmacologic and lifestyle changes to help patients minimize hair loss:
1. Recommend a biotin supplement. Valproate can cause biotin deficiency and may lead to low serum and liver tissue biotinidase enzyme4; a major clinical manifestation of biotin deficiency is alopecia.
2. Tell patients to avoid taking valproate during meals to prevent its chelating effect on food. The chelating effect of valproate makes metals that facilitate hair growth, such as zinc and selenium, unavailable for absorption.5
3. Recommend zinc and selenium supplements, which can help stop further hair loss and regenerate hair.5
4. Suggest practical advice for hair care, including using soft brushes and mild shampoos and avoiding dyes, heated curlers, and hair dryers.
5. Consider minoxidil therapy. However, this is an expensive option and there are no cases documenting its use for alopecia caused by mood stabilizers.
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Castro-Gago M, Gómez-Lado C, Eirís-Puñal J, et al. Serum biotinidase activity in children treated with valproic acid and carbamazepine. J Child Neurol. 2010;25(1):32-35.
2. Patrizi A, Savoia F, Negosanti F, et al. Telogen effluvium caused by magnesium valproate and lamotrigine. Acta Derm Venereol. 2005;85(1):77-78.
3. Mercke Y, Sheng H, Khan T, et al. Hair loss in psychopharmacology. Ann Clin Psychiatry. 2000;12(1):35-42.
4. Yilmaz Y, Tasdemir HA, Paksu MS. The influence of valproic acid treatment on hair and serum zinc levels and serum biotinidase activity. Eur J Paediatr Neurol. 2009;13(5):439-443.
4. Fatemi SH, Calabrese JR. Treatment of valproate-induced alopecia. Ann Pharmacother. 1995;29(12):1302.-
1. Castro-Gago M, Gómez-Lado C, Eirís-Puñal J, et al. Serum biotinidase activity in children treated with valproic acid and carbamazepine. J Child Neurol. 2010;25(1):32-35.
2. Patrizi A, Savoia F, Negosanti F, et al. Telogen effluvium caused by magnesium valproate and lamotrigine. Acta Derm Venereol. 2005;85(1):77-78.
3. Mercke Y, Sheng H, Khan T, et al. Hair loss in psychopharmacology. Ann Clin Psychiatry. 2000;12(1):35-42.
4. Yilmaz Y, Tasdemir HA, Paksu MS. The influence of valproic acid treatment on hair and serum zinc levels and serum biotinidase activity. Eur J Paediatr Neurol. 2009;13(5):439-443.
4. Fatemi SH, Calabrese JR. Treatment of valproate-induced alopecia. Ann Pharmacother. 1995;29(12):1302.-
Treating Bipolar Depression Depends on Evidence, Judgment
PARIS – Existing evidence on the best ways to treat bipolar depression is limited, and must balance against what works in the real world based on empirical experience. When treating bipolar depression "we are in the land of the uncertain, where [psychiatrists] must improvise and do their best with what’s available," Dr. Andrew A. Nierenberg said at the annual congress of the European College of Neuropsychopharmacology.
The trials that get drugs approved by the Food and Drug Administration often do not inform routine care. Patients in trials often differ from "real" patients, generally have milder disease, and are less susceptible to the worst outcomes. The published evidence base for treating bipolar depression should not be viewed as synonymous with best practice. Treatment is not a cookbook, and evidence-based medicine is very difficult to actually implement, said Dr. Nierenberg, medical director of the bipolar clinic and research program at Massachusetts General Hospital, and professor of psychiatry at Harvard Medical School, both in Boston.
Treatment of patients with bipolar disorder in actual practice requires personalization, including prescribing agents that work and expecting patients to continue to take them despite possible adverse effects. Published evidence leaves it unclear how best to treat any specific patient, he said. That requires not only evidence but also clinical experience and knowledge of the results obtained by others, followed by feedback and outcomes assessment to guide future changes in treatment.
Perhaps the biggest question in the treatment of bipolar depression today is whether antidepressants work. A 2004 meta-analysis said they did (Am. J. Psychiatry 2004;161:1537-47), but this was "a terrible" meta-analysis because the overall numbers of patients were small, and the results from a single study heavily influenced the overall meta-analysis results, Dr. Nierenberg said. In addition, results from the STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) trial showed that adding an antidepressant to the mood stabilizer lithium gave no significant added benefit (N. Engl. J. Med. 2007;356:1711-22).
Taken together, the literature provides insufficient evidence to document a beneficial role for antidepressants in the treatment of bipolar depression, along with some evidence against any efficacy, yet Dr. Nierenberg said he prescribes an antidepressant as monotherapy or as an add-on treatment to many patients, as do many other psychiatrists. Psychiatrists generally feel that the data against adding an antidepressant are unconvincing, because they have seen antidepressants work on many prior patients. "The data are inconsistent with their clinical experience," he noted.
The roles of several other drugs or drug combinations also feature conflicts between the evidence base and their use in everyday practice.
The combination of olanzapine and fluoxetine showed efficacy in a highly influential 2003 study (Arch. Gen. Psychiatry 2003;60:1079-88). But the olanzapine and fluoxetine pairing is seldom used today because of concerns that it causes weight gain and tends to trigger metabolic syndrome. It’s ironic that olanzapine and fluoxetine is an FDA-approved combination that few patients actually receive, he said. Patients don’t like to gain weight, and when they do, they often stop taking the drugs.
Lamotrigine showed efficacy for treating bipolar depression in a 1999 study (J. Clin. Psychiatry 1999;60:79-88), but failed to show substantial efficacy in five other studies. In addition, lamotrigine failed to receive FDA approval for treating acute depression. Despite that, U.S. physicians appear to have embraced lamotrigine for treating depression in patients with bipolar disorder, "a discrepancy between what the literature says and what people actually do," Dr. Nierenberg noted. Results from a 2009 study showed that adding lamotrigine to lithium led to an improved decrease in depression, compared with lithium plus placebo (J. Clin. Psychiatry 2009;70:223-31), but physicians also prescribe lamotrigine monotherapy, even though published findings do not support that approach.
Perhaps the drug with the best clinical performance on paper is quetiapine, which has produced the largest effect size seen in depression (Am. J. Psychiatry 2005;162:1351-60), both monopolar and bipolar, and has had efficacy for mania, anxiety, insomnia, and psychosis. Based on this evidence, Dr. Nierenberg said that he would expect the extensive prescribing of quetiapine, but in reality, few patients receive it. Again, it’s a drug with significant side effects, including sedation and weight gain.
Other approaches to treating bipolar depression that are often used as first-line therapy, despite a poor evidence base, include optimization of a regimen of lithium, valproate, or carbamazepine that the patient might already take. Psychotherapy also can help, but less so once a patient has had 10-20 depressive or manic episodes. And electroconvulsive therapy is an important option for treatment-refractory bipolar depression. But the right treatment in many other clinical situations might involve unclear options, such as how to handle patients who are already on antimania treatment, and how to continue an antidepressant that produced partial improvement. Common complications of bipolar depression that can influence treatment decisions include attention-deficit/hyperactivity disorder, substance abuse, a chaotic life, and poor drug compliance. These and other factors make it impossible to rely just on evidence when choosing a patient’s treatment, Dr. Nierenberg said.
Dr. Nierenberg said he has a patent pending on combined treatment of mood disorders with buspirone, bupropion, and melatonin, and he co-owns a copyright on a structured clinical interview for the Montgomery-Åsberg Depression Rating Scale. He said he has received honoraria from Eli Lilly, AstraZeneca, Forest, and Janssen, and that he has received research grants from Pam Labs, Pfizer, and Shire.
PARIS – Existing evidence on the best ways to treat bipolar depression is limited, and must balance against what works in the real world based on empirical experience. When treating bipolar depression "we are in the land of the uncertain, where [psychiatrists] must improvise and do their best with what’s available," Dr. Andrew A. Nierenberg said at the annual congress of the European College of Neuropsychopharmacology.
The trials that get drugs approved by the Food and Drug Administration often do not inform routine care. Patients in trials often differ from "real" patients, generally have milder disease, and are less susceptible to the worst outcomes. The published evidence base for treating bipolar depression should not be viewed as synonymous with best practice. Treatment is not a cookbook, and evidence-based medicine is very difficult to actually implement, said Dr. Nierenberg, medical director of the bipolar clinic and research program at Massachusetts General Hospital, and professor of psychiatry at Harvard Medical School, both in Boston.
Treatment of patients with bipolar disorder in actual practice requires personalization, including prescribing agents that work and expecting patients to continue to take them despite possible adverse effects. Published evidence leaves it unclear how best to treat any specific patient, he said. That requires not only evidence but also clinical experience and knowledge of the results obtained by others, followed by feedback and outcomes assessment to guide future changes in treatment.
Perhaps the biggest question in the treatment of bipolar depression today is whether antidepressants work. A 2004 meta-analysis said they did (Am. J. Psychiatry 2004;161:1537-47), but this was "a terrible" meta-analysis because the overall numbers of patients were small, and the results from a single study heavily influenced the overall meta-analysis results, Dr. Nierenberg said. In addition, results from the STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) trial showed that adding an antidepressant to the mood stabilizer lithium gave no significant added benefit (N. Engl. J. Med. 2007;356:1711-22).
Taken together, the literature provides insufficient evidence to document a beneficial role for antidepressants in the treatment of bipolar depression, along with some evidence against any efficacy, yet Dr. Nierenberg said he prescribes an antidepressant as monotherapy or as an add-on treatment to many patients, as do many other psychiatrists. Psychiatrists generally feel that the data against adding an antidepressant are unconvincing, because they have seen antidepressants work on many prior patients. "The data are inconsistent with their clinical experience," he noted.
The roles of several other drugs or drug combinations also feature conflicts between the evidence base and their use in everyday practice.
The combination of olanzapine and fluoxetine showed efficacy in a highly influential 2003 study (Arch. Gen. Psychiatry 2003;60:1079-88). But the olanzapine and fluoxetine pairing is seldom used today because of concerns that it causes weight gain and tends to trigger metabolic syndrome. It’s ironic that olanzapine and fluoxetine is an FDA-approved combination that few patients actually receive, he said. Patients don’t like to gain weight, and when they do, they often stop taking the drugs.
Lamotrigine showed efficacy for treating bipolar depression in a 1999 study (J. Clin. Psychiatry 1999;60:79-88), but failed to show substantial efficacy in five other studies. In addition, lamotrigine failed to receive FDA approval for treating acute depression. Despite that, U.S. physicians appear to have embraced lamotrigine for treating depression in patients with bipolar disorder, "a discrepancy between what the literature says and what people actually do," Dr. Nierenberg noted. Results from a 2009 study showed that adding lamotrigine to lithium led to an improved decrease in depression, compared with lithium plus placebo (J. Clin. Psychiatry 2009;70:223-31), but physicians also prescribe lamotrigine monotherapy, even though published findings do not support that approach.
Perhaps the drug with the best clinical performance on paper is quetiapine, which has produced the largest effect size seen in depression (Am. J. Psychiatry 2005;162:1351-60), both monopolar and bipolar, and has had efficacy for mania, anxiety, insomnia, and psychosis. Based on this evidence, Dr. Nierenberg said that he would expect the extensive prescribing of quetiapine, but in reality, few patients receive it. Again, it’s a drug with significant side effects, including sedation and weight gain.
Other approaches to treating bipolar depression that are often used as first-line therapy, despite a poor evidence base, include optimization of a regimen of lithium, valproate, or carbamazepine that the patient might already take. Psychotherapy also can help, but less so once a patient has had 10-20 depressive or manic episodes. And electroconvulsive therapy is an important option for treatment-refractory bipolar depression. But the right treatment in many other clinical situations might involve unclear options, such as how to handle patients who are already on antimania treatment, and how to continue an antidepressant that produced partial improvement. Common complications of bipolar depression that can influence treatment decisions include attention-deficit/hyperactivity disorder, substance abuse, a chaotic life, and poor drug compliance. These and other factors make it impossible to rely just on evidence when choosing a patient’s treatment, Dr. Nierenberg said.
Dr. Nierenberg said he has a patent pending on combined treatment of mood disorders with buspirone, bupropion, and melatonin, and he co-owns a copyright on a structured clinical interview for the Montgomery-Åsberg Depression Rating Scale. He said he has received honoraria from Eli Lilly, AstraZeneca, Forest, and Janssen, and that he has received research grants from Pam Labs, Pfizer, and Shire.
PARIS – Existing evidence on the best ways to treat bipolar depression is limited, and must balance against what works in the real world based on empirical experience. When treating bipolar depression "we are in the land of the uncertain, where [psychiatrists] must improvise and do their best with what’s available," Dr. Andrew A. Nierenberg said at the annual congress of the European College of Neuropsychopharmacology.
The trials that get drugs approved by the Food and Drug Administration often do not inform routine care. Patients in trials often differ from "real" patients, generally have milder disease, and are less susceptible to the worst outcomes. The published evidence base for treating bipolar depression should not be viewed as synonymous with best practice. Treatment is not a cookbook, and evidence-based medicine is very difficult to actually implement, said Dr. Nierenberg, medical director of the bipolar clinic and research program at Massachusetts General Hospital, and professor of psychiatry at Harvard Medical School, both in Boston.
Treatment of patients with bipolar disorder in actual practice requires personalization, including prescribing agents that work and expecting patients to continue to take them despite possible adverse effects. Published evidence leaves it unclear how best to treat any specific patient, he said. That requires not only evidence but also clinical experience and knowledge of the results obtained by others, followed by feedback and outcomes assessment to guide future changes in treatment.
Perhaps the biggest question in the treatment of bipolar depression today is whether antidepressants work. A 2004 meta-analysis said they did (Am. J. Psychiatry 2004;161:1537-47), but this was "a terrible" meta-analysis because the overall numbers of patients were small, and the results from a single study heavily influenced the overall meta-analysis results, Dr. Nierenberg said. In addition, results from the STEP-BD (Systematic Treatment Enhancement Program for Bipolar Disorder) trial showed that adding an antidepressant to the mood stabilizer lithium gave no significant added benefit (N. Engl. J. Med. 2007;356:1711-22).
Taken together, the literature provides insufficient evidence to document a beneficial role for antidepressants in the treatment of bipolar depression, along with some evidence against any efficacy, yet Dr. Nierenberg said he prescribes an antidepressant as monotherapy or as an add-on treatment to many patients, as do many other psychiatrists. Psychiatrists generally feel that the data against adding an antidepressant are unconvincing, because they have seen antidepressants work on many prior patients. "The data are inconsistent with their clinical experience," he noted.
The roles of several other drugs or drug combinations also feature conflicts between the evidence base and their use in everyday practice.
The combination of olanzapine and fluoxetine showed efficacy in a highly influential 2003 study (Arch. Gen. Psychiatry 2003;60:1079-88). But the olanzapine and fluoxetine pairing is seldom used today because of concerns that it causes weight gain and tends to trigger metabolic syndrome. It’s ironic that olanzapine and fluoxetine is an FDA-approved combination that few patients actually receive, he said. Patients don’t like to gain weight, and when they do, they often stop taking the drugs.
Lamotrigine showed efficacy for treating bipolar depression in a 1999 study (J. Clin. Psychiatry 1999;60:79-88), but failed to show substantial efficacy in five other studies. In addition, lamotrigine failed to receive FDA approval for treating acute depression. Despite that, U.S. physicians appear to have embraced lamotrigine for treating depression in patients with bipolar disorder, "a discrepancy between what the literature says and what people actually do," Dr. Nierenberg noted. Results from a 2009 study showed that adding lamotrigine to lithium led to an improved decrease in depression, compared with lithium plus placebo (J. Clin. Psychiatry 2009;70:223-31), but physicians also prescribe lamotrigine monotherapy, even though published findings do not support that approach.
Perhaps the drug with the best clinical performance on paper is quetiapine, which has produced the largest effect size seen in depression (Am. J. Psychiatry 2005;162:1351-60), both monopolar and bipolar, and has had efficacy for mania, anxiety, insomnia, and psychosis. Based on this evidence, Dr. Nierenberg said that he would expect the extensive prescribing of quetiapine, but in reality, few patients receive it. Again, it’s a drug with significant side effects, including sedation and weight gain.
Other approaches to treating bipolar depression that are often used as first-line therapy, despite a poor evidence base, include optimization of a regimen of lithium, valproate, or carbamazepine that the patient might already take. Psychotherapy also can help, but less so once a patient has had 10-20 depressive or manic episodes. And electroconvulsive therapy is an important option for treatment-refractory bipolar depression. But the right treatment in many other clinical situations might involve unclear options, such as how to handle patients who are already on antimania treatment, and how to continue an antidepressant that produced partial improvement. Common complications of bipolar depression that can influence treatment decisions include attention-deficit/hyperactivity disorder, substance abuse, a chaotic life, and poor drug compliance. These and other factors make it impossible to rely just on evidence when choosing a patient’s treatment, Dr. Nierenberg said.
Dr. Nierenberg said he has a patent pending on combined treatment of mood disorders with buspirone, bupropion, and melatonin, and he co-owns a copyright on a structured clinical interview for the Montgomery-Åsberg Depression Rating Scale. He said he has received honoraria from Eli Lilly, AstraZeneca, Forest, and Janssen, and that he has received research grants from Pam Labs, Pfizer, and Shire.
EXPERT ANALYSIS FROM THE ANNUAL CONGRESS OF THE EUROPEAN COLLEGE OF NEURO-
PSYCHOPHARMACOLOGY
A curious case of depression
Discuss this article at www.facebook.com/CurrentPsychiatry
Mr. Z, age 61, is referred by his primary care clinician to the hospital’s medical service with increasing depressive symptoms and non-pruritic rash. He has a history of bipolar I disorder for >30 years. When the primary care physician evaluated Mr. Z, his vitals were normal, but blood work revealed mild anemia and thrombocytopenia of 34 x103/μL, which prompted referral to the hospital. During admission, the psychiatric consultation service is called to evaluate Mr. Z’s depressive symptoms.
Mr. Z reports having chronic sleep problems and feeling cold and tired, shivering at times, but has no pain. He says he’s worried because he feels severely depressed, worthless, and hopeless, but denies suicidal ideation and psychosis. Mr. Z says he started experiencing increasingly depressed mood, anhedonia, insomnia, fatigue, poor appetite, and concentration 2 months ago. At that time his outpatient psychiatrist started Mr. Z on risperidone, 6 mg/d, and divalproex, 1,500 mg at bedtime because of emerging mood symptoms, after he was off medication for 7 months. Mr. Z attributed his worsened mood symptoms to being overwhelmed by several psychosocial stressors, including going through a complicated divorce, financial problems, and homelessness after being evicted from his apartment.
A review of Mr. Z’s psychiatric history reveals several remote hospitalizations—the last was 7 years ago—for escalated manic symptoms after he stopped taking his medication. He denies past suicide attempts. Mr. Z says he is compliant with his current medication regimen—risperidone, 6 mg/d, and divalproex, 1,500 mg at bedtime. He denies illicit drug use and says he drinks “a couple of beers, mostly on weekends.” Family history is positive for depression and bipolar II disorder.
His medical history is significant for hypothyroidism after goiter removal 6 years ago, for which he takes levothyroxine, 150 mcg/d, and a sports injury-related splenectomy in childhood. He reports no allergies. Vital signs at the time of admission are temperature, 99.1°F; pulse, 98 beats per minute; respiration, 16 breaths per minute; blood pressure, 123/73 mm/Hg; and oxygen saturation, 97%.
During the interview, Mr. Z presents with tired facies and exhibits psychomotor retardation. He has to force himself to stay engaged in the evaluation and maintain eye contact. His speech is clear, regular, and soft. Mr. Z says he is “very depressed”; his affect is constricted, almost flat, stable, and consistent with depressed mood. His thought process is linear and somewhat concrete and his thought content is notable for hopelessness, although Mr. Z continues to deny suicidal or homicidal ideations. No hallucinations or apparent delusions are noted. Insight and judgment are fair. Mr. Z understands his current mental state; however, he displays some lack of knowledge regarding his current hospitalization. Cognition is intact.
The authors’ observations
The differential diagnosis in patients presenting with mood changes is extensive (Table 1)1 and in Mr. Z’s case includes several precipitating and perpetuating factors. Mr. Z presents with severe depressive symptoms and meets DSM-IV-TR criteria for a major depressive episode (MDE). This presentation is not typical of his bipolar I disorder because Mr. Z has never experienced an MDE and usually presents with escalating hypomanic/manic symptoms in the context of medication nonadherence. Nevertheless, Mr. Z has several risk factors for severe depression, including a family psychiatric history, multiple enduring social stressors and life crises, and medical conditions.
In the general population, the lifetime risk for developing depression is 8% to 17%.2 The risk of developing a mood disorder increases significantly if a first-degree relative is diagnosed with a mood disorder; the relative risk is 10.3 for bipolar disorder and 3.2 for depression.3 Additionally, Mr. Z is going through a complicated divorce, has financial problems, and is homeless, all of which could trigger an MDE. Furthermore, hypothyroidism shares many symptoms of depression, including fatigue, lethargy, anhedonia, cold intolerance, and low mood; mental status changes frequently are the initial presentation of thyroid problems.4 Physicians started Mr. Z on a new medication regimen (risperidone and divalproex) to control mood instability, which coincided with symptom onset. Atypical antipsychotics have been reported to precipitate depressive symptoms; their side effect profile includes extrapyramidal effects, such as flat affect, which can be mistaken for depression.5 Rapid valproate titration can mimic neurovegetative symptoms of depression and cause dose-dependent thrombocytopenia and rash, which could explain his initial presentation.6 Finally, Mr. Z’s history of traumatic splenectomy, change in mental status, and thrombocytopenia suggest an infectious etiology.
Table 1
Differential diagnosis in patients presenting with mood changes
| Cerebrovascular disease |
| Degenerative disorders (Parkinson’s disease, Huntington’s disease, Wilson’s disease) |
| Demyelinating disorders (multiple sclerosis, amyotrophic lateral sclerosis, lipid storage disease) |
| Endocrine disorders (Addison’s disease, Cushing’s disease, hyperthyroidism, hypothyroidism, hyperparathyroidism, pituitary dysfunction) |
| Epilepsy |
| Infectious diseases |
| Immune diseases |
| Metabolic encephalopathy |
| Neoplasm |
| Nutritional deficits (thiamine, niacin, vitamin B12) |
| Primary psychiatric disorders (mood disorders, dementia, sleep disorders) |
| Substance use |
| Toxins/medications |
| Traumatic brain injury |
| Source: Reference 1 |
Possible infectious causes
The increased prevalence of immune suppression due to human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or from therapeutic modalities such as cancer therapy or splenectomy has led to an increased number of chronic CNS infections, manifesting with an array of neuropsychiatric symptoms and nonspecific physiological reactions.1,7 Mr. Z complains of a 2-month period of worsening depression that could suggest an infectious process with an insidious onset. Some infectious agents that can cause chronic CNS infection and encephalopathy are presented in Table 2.8 HIV, tuberculosis, syphilis, Lyme disease, and herpes simplex virus are becoming more prevalent and can present with neuropsychiatric symptoms.1 For example, in addition to thrombocytopenia and low-grade fever, patients with HIV may exhibit a broad range of neuropsychiatric symptoms such as cognitive problems, impaired executive and motor functioning, sleep disturbance, and anxiety. These patients frequently present with low mood and neurovegetative symptoms of depression.7 Similarly, the same tick responsible for Lyme disease infection can transmit other infectious agents that can cause thrombocytopenia, including Babesia, Ehrlichia chaffeensis, Anaplasma phagocytophilum, and human Ewingii ehrlichiosis.
The authors’ observations
Diagnosis of a mood change, particularly an MDE, is clinical, based on careful psychiatric evaluation using standardized criteria rather than a specific lab test. However, some laboratory studies (Table 3)1 are useful in differentiating medical illnesses that may present with depression. Mr. Z’s presentation warrants investigating these tests. His history of traumatic splenectomy and night sweats suggests an infection. The team’s initial recommendations include laboratory tests, discontinuing divalproex because it may be causing thrombocytopenia, and decreasing risperidone to 2 mg/d to improve his fatigue and possibly developed extrapyramidal symptoms.
Table 2
Potential infectious causes of chronic encephalopathy
| Type of infection | Organism/disease |
|---|---|
| Mycobacterial | Mycobacterium tuberculosis |
| Spirochetal | Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme disease), Leptospira |
| Bacterial | Brucella, Listeria, Nocardia, Actinomyces israelii, Whipple’s disease |
| Viral | HIV/AIDS, cytomegalovirus, varicella zoster virus, herpes simplex virus, enterovirus |
| Fungal | Histoplasmosis, coccidiosis, sporothrix, Blastomyces, Cryptococcus |
| Parasitic | Toxoplasmosis, taenia solium (cysticercosis), Schistosoma, Acanthamoeba |
| AIDS: acquired immunodeficiency syndrome; HIV: human immunodeficiency virus Source: Reference 8 | |
Table 3
Differentiating medical illnesses that may mimic depression
| Laboratory tests |
|
| Imaging studies |
|
| Other tests |
|
| Procedures |
|
| ABG: arterial blood gases; CBC: complete blood count; EEG: electroencephalogram; ELISA: enzyme-linked immunosorbent assay; HIV: human immunodeficiency virus; VDRL: venereal disease research laboratory Source: Reference 1 |
TREATMENT: Cause revealed
Mr. Z develops a persistent fever of 102°F with continuous profuse sweating and a hypotensive episode. Blood work reveals mild anemia, thrombocytopenia, and increased coagulation parameters with high D-dimer and low fibrinogen, consistent with diagnosis of disseminated intravascular coagulation (DIC) secondary to infectious etiology. Thyroid and HIV tests are negative. After further evaluation, Mr. Z remembers that 4 months earlier he removed several ticks from his legs after hunting; he also remembers experiencing shivering and night sweats several weeks before he was hospitalized. His blood smear is positive for babesiosis and further testing confirms positive Lyme antibodies. Mr. Z is started on aggressive hemodynamic stabilization and a pathogen-tailored course of antibiotics for several weeks. This results in improvement and discharge home in a stable condition. His depression and fatigue improve but do not fully remit by the time he is discharged.
The authors’ observations
Lyme disease is one of the fastest-growing infectious diseases in the United States.9 The prevalence of positive Lyme antibodies is 30% higher in psychiatric populations than the general population.10 Lyme disease is transmitted by deer tick bite, often undetected, that is infected with spirochete Borrelia burgdorferi. To be infectious, ticks need to be attached to the skin for 24 to 48 hours,11,12 although individual cases have reported transmission in <24 hours. The clinical manifestations of Lyme disease can be divided into 3 phases:
- early localized phase, characterized by the distinctive skin lesion erythema migrans with or without constitutional symptoms
- early disseminated phase, characterized by multiple erythema migrans lesions and neurologic and/or cardiac findings
- late or chronic disease associated with intermittent/persistent arthritis and/or neurologic problems.11,13
The clinical features of each stage frequently overlap and some patients in a later stage of Lyme disease do not have prior signs or symptoms of the disease. Because it is a multisystem disease, Lyme disease can attack the CNS in the form of neuroborreliosis, a clinical diagnosis, without involving other systems, and its neuropsychiatric manifestations can resemble neurosyphilis because both organisms are spirochetes.11,13,14 CNS disorders have been found in up to 40% of Lyme disease cases.11 In neuroborreliosis, cognitive problems usually predominate; however, neuroborreliosis can mimic multiple brain diseases presenting with various neurologic and psychiatric symptoms (Table 4)14,15 and can present at any time after the tick bite. Furthermore neuroborreliosis is difficult to diagnose because symptoms may remain dormant and emerge after several years.11,13,14Borrelia burgdorferi is challenging to isolate and grow in the lab, and enzyme-linked immunosorbent assay (ELISA) testing for antibodies is highly specific but not very sensitive,16 frequently giving false negative results. Western blot confirms the diagnosis.
Table 4
Late-stage neuropsychiatric symptoms of Lyme disease
| Cognitive problems, memory problems, forgetfulness, slowing of thought processing, dysfunction in visuospatial orientation, dyslexia |
| Depression |
| Mood swings |
| Psychosis |
| Violent behavior/irritability |
| OCD |
| Anxiety |
| Panic attacks |
| Sleep disorders |
| Seizures |
| ADHD-like symptoms |
| Autism-like behavior |
| Chronic fatigue syndrome |
| Fibromyalgia |
| ADHD: attention-deficit/hyperactivity disorder; OCD: obsessive-compulsive disorder Source: References 14,15 |
Mr. Z’s presentation also reflects co-infection with babesiosis. Babesia is malaria-like protozoa diagnosed by blood smear that can cause a fatal illness in immuno-compromised patients. The clinical picture varies from mild symptoms such as night sweats, chills, arthralgias, and anorexia with thrombocytopenia to severe and potentially fatal outcomes in immunocompromised patients, including DIC, acute renal failure, sepsis, congestive heart failure, and myocardial infarction.11 Risk factors for the severest forms of babesiosis are age >50, co-infection with Lyme disease, and splenectomy,11 all of which were present in Mr. Z. Co-infected patients experience fatigue, headache, anorexia, and emotional lability more frequently than those with Lyme disease alone.12
Treatment options
Treatment of Lyme disease/neuroborreliosis is complex. The mainstay approach is antibiotics. Despite adequate treatment, many patients experience continued impairment, including chronic pain, fatigue, and cognitive and psychiatric symptoms.11,14 There is some evidence Borrelia burgdorferi can persist and re-emerge after adequate treatment.14,17 The National Institute of Health sponsored several clinical trials of prolonged antibiotic treatment for chronic Lyme disease. Some results suggested improvement in fatigue and cognitive function, although these results were not sustained.18
There is a strong link between mental illness and increased prevalence of positive Lyme disease antibodies.10 Several studies report increased risk of infection during psychological stress that may be related to an altered immune system response.19 Evidence suggests that Borrelia burgdorferi can alter immune system response, making T cells more reactive not only to Borrelia burgdorferi antigens but also to host antigens,20 creating autoimmune inflammatory reactions that could explain chronic neuropsychiatric symptoms. It appears Lyme disease antigens can mimic certain autoantigens (for example, in the thyroid gland).21 Whether there is a role for autoimmune therapy in treating chronic symptoms needs to be investigated.
Once Lyme disease is diagnosed, educating patients and families becomes an important part of treatment because many patients report feeling stigmatized by the diagnosis. Referral to a Lyme disease support group may be beneficial. Patients with neuropsychiatric symptoms that persist after antibiotic treatment should be offered symptom-based treatment, including medications and therapy.
Related Resource
- Centers for Disease Control and Prevention. Lyme disease: Resources for clinicians. www.cdc.gov/lyme/healthcare/clinicians.html.
Drug Brand Names
- Divalproex sodium • Depakote
- Levothyroxine • Levoxyl, Synthroid
- Risperidone • Risperdal
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Stern TA, Rosenbaum JF, Fava M, et al. eds. Massachusetts General Hospital comprehensive clinical psychiatry. Philadelphia, PA: Mosby; 2008;257-277.
2. Andrade L, Caraveo-Anduaga JJ, Berglund P, et al. The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res. 2003;12(1):3-21.
3. Merikangas KR, Low NC. The epidemiology of mood disorders. Curr Psychiatry Rep. 2004;6:411-421.
4. Brown GM. Psychiatric and neurologic aspects of endocrine disease. In Krieger DT Hughes JC, eds. Neuroendocrinology. Sunderland, MA: Sinauer Associates; 1980;185-194.
5. Maguire GA. Comprehensive understanding of schizophrenia and its treatment. Am J Health Syst Pharm. 2002;59(17 suppl 5):S4-S11.
6. Dreifuss FE, Langer DH. Side effects of valproate. Am J Med. 1988;84(1A):34-41.
7. Perry S, Jacobsen P. Neuropsychiatric manifestations of AIDS-spectrum disorders. Hosp Community Psychiatry. 1986;37:135-142.
8. Hildebrand J, Aoun M. Chronic meningitis: still a diagnostic challenge. J Neurol. 2003;250(6):653-660.
9. Bacon RM, Kugeler KJ, Mead PS. Centers for Disease Control and Prevention (CDC). Surveillance for Lyme disease—United States 1992-2006. MMWR Surveill Summ. 2008;57(10):1-9.
10. Hájek T, Pasková B, Janovská D, et al. Higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients than in healthy subjects. Am J Psychiatry. 2002;159:297-301.
11. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.
12. Krause PJ, Telford SR 3rd, Spielman A, et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. 1996;275(21):1657-1660.
13. Hildenbrand P, Craven DE, Jones R, et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol. 2009;30:1079-1087.
14. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151:1571-1583.
15. Fallon BA, Nields JA, Burrascano JJ, et al. The neuropsychiatric manifestations of Lyme borreliosis. Psychiatr Q. 1992;63(1):95-117.
16. Stricker RB, Johnson L. Lyme wars: let’s tackle the testing. BMJ. 2007;335:1008.-
17. Hodzic E, Feng S, Holden K, et al. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52(5):1728-1736.
18. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.
19. Sheridan JF, Dobbs C, Brown D, et al. Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection. Clin Microbiol Rev. 1994;7(2):200-212.
20. Yssel H, Shanafelt MC, Soderberg C, et al. Borrelia burgdorferi activates a T helper 1-like T cell subset in Lyme arthritis. J Exp Med. 1991;174:593-601.
21. Benvenga S, Guarneri F, Vaccaro M, et al. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid. 2004;14(11):964-966.
Discuss this article at www.facebook.com/CurrentPsychiatry
Mr. Z, age 61, is referred by his primary care clinician to the hospital’s medical service with increasing depressive symptoms and non-pruritic rash. He has a history of bipolar I disorder for >30 years. When the primary care physician evaluated Mr. Z, his vitals were normal, but blood work revealed mild anemia and thrombocytopenia of 34 x103/μL, which prompted referral to the hospital. During admission, the psychiatric consultation service is called to evaluate Mr. Z’s depressive symptoms.
Mr. Z reports having chronic sleep problems and feeling cold and tired, shivering at times, but has no pain. He says he’s worried because he feels severely depressed, worthless, and hopeless, but denies suicidal ideation and psychosis. Mr. Z says he started experiencing increasingly depressed mood, anhedonia, insomnia, fatigue, poor appetite, and concentration 2 months ago. At that time his outpatient psychiatrist started Mr. Z on risperidone, 6 mg/d, and divalproex, 1,500 mg at bedtime because of emerging mood symptoms, after he was off medication for 7 months. Mr. Z attributed his worsened mood symptoms to being overwhelmed by several psychosocial stressors, including going through a complicated divorce, financial problems, and homelessness after being evicted from his apartment.
A review of Mr. Z’s psychiatric history reveals several remote hospitalizations—the last was 7 years ago—for escalated manic symptoms after he stopped taking his medication. He denies past suicide attempts. Mr. Z says he is compliant with his current medication regimen—risperidone, 6 mg/d, and divalproex, 1,500 mg at bedtime. He denies illicit drug use and says he drinks “a couple of beers, mostly on weekends.” Family history is positive for depression and bipolar II disorder.
His medical history is significant for hypothyroidism after goiter removal 6 years ago, for which he takes levothyroxine, 150 mcg/d, and a sports injury-related splenectomy in childhood. He reports no allergies. Vital signs at the time of admission are temperature, 99.1°F; pulse, 98 beats per minute; respiration, 16 breaths per minute; blood pressure, 123/73 mm/Hg; and oxygen saturation, 97%.
During the interview, Mr. Z presents with tired facies and exhibits psychomotor retardation. He has to force himself to stay engaged in the evaluation and maintain eye contact. His speech is clear, regular, and soft. Mr. Z says he is “very depressed”; his affect is constricted, almost flat, stable, and consistent with depressed mood. His thought process is linear and somewhat concrete and his thought content is notable for hopelessness, although Mr. Z continues to deny suicidal or homicidal ideations. No hallucinations or apparent delusions are noted. Insight and judgment are fair. Mr. Z understands his current mental state; however, he displays some lack of knowledge regarding his current hospitalization. Cognition is intact.
The authors’ observations
The differential diagnosis in patients presenting with mood changes is extensive (Table 1)1 and in Mr. Z’s case includes several precipitating and perpetuating factors. Mr. Z presents with severe depressive symptoms and meets DSM-IV-TR criteria for a major depressive episode (MDE). This presentation is not typical of his bipolar I disorder because Mr. Z has never experienced an MDE and usually presents with escalating hypomanic/manic symptoms in the context of medication nonadherence. Nevertheless, Mr. Z has several risk factors for severe depression, including a family psychiatric history, multiple enduring social stressors and life crises, and medical conditions.
In the general population, the lifetime risk for developing depression is 8% to 17%.2 The risk of developing a mood disorder increases significantly if a first-degree relative is diagnosed with a mood disorder; the relative risk is 10.3 for bipolar disorder and 3.2 for depression.3 Additionally, Mr. Z is going through a complicated divorce, has financial problems, and is homeless, all of which could trigger an MDE. Furthermore, hypothyroidism shares many symptoms of depression, including fatigue, lethargy, anhedonia, cold intolerance, and low mood; mental status changes frequently are the initial presentation of thyroid problems.4 Physicians started Mr. Z on a new medication regimen (risperidone and divalproex) to control mood instability, which coincided with symptom onset. Atypical antipsychotics have been reported to precipitate depressive symptoms; their side effect profile includes extrapyramidal effects, such as flat affect, which can be mistaken for depression.5 Rapid valproate titration can mimic neurovegetative symptoms of depression and cause dose-dependent thrombocytopenia and rash, which could explain his initial presentation.6 Finally, Mr. Z’s history of traumatic splenectomy, change in mental status, and thrombocytopenia suggest an infectious etiology.
Table 1
Differential diagnosis in patients presenting with mood changes
| Cerebrovascular disease |
| Degenerative disorders (Parkinson’s disease, Huntington’s disease, Wilson’s disease) |
| Demyelinating disorders (multiple sclerosis, amyotrophic lateral sclerosis, lipid storage disease) |
| Endocrine disorders (Addison’s disease, Cushing’s disease, hyperthyroidism, hypothyroidism, hyperparathyroidism, pituitary dysfunction) |
| Epilepsy |
| Infectious diseases |
| Immune diseases |
| Metabolic encephalopathy |
| Neoplasm |
| Nutritional deficits (thiamine, niacin, vitamin B12) |
| Primary psychiatric disorders (mood disorders, dementia, sleep disorders) |
| Substance use |
| Toxins/medications |
| Traumatic brain injury |
| Source: Reference 1 |
Possible infectious causes
The increased prevalence of immune suppression due to human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or from therapeutic modalities such as cancer therapy or splenectomy has led to an increased number of chronic CNS infections, manifesting with an array of neuropsychiatric symptoms and nonspecific physiological reactions.1,7 Mr. Z complains of a 2-month period of worsening depression that could suggest an infectious process with an insidious onset. Some infectious agents that can cause chronic CNS infection and encephalopathy are presented in Table 2.8 HIV, tuberculosis, syphilis, Lyme disease, and herpes simplex virus are becoming more prevalent and can present with neuropsychiatric symptoms.1 For example, in addition to thrombocytopenia and low-grade fever, patients with HIV may exhibit a broad range of neuropsychiatric symptoms such as cognitive problems, impaired executive and motor functioning, sleep disturbance, and anxiety. These patients frequently present with low mood and neurovegetative symptoms of depression.7 Similarly, the same tick responsible for Lyme disease infection can transmit other infectious agents that can cause thrombocytopenia, including Babesia, Ehrlichia chaffeensis, Anaplasma phagocytophilum, and human Ewingii ehrlichiosis.
The authors’ observations
Diagnosis of a mood change, particularly an MDE, is clinical, based on careful psychiatric evaluation using standardized criteria rather than a specific lab test. However, some laboratory studies (Table 3)1 are useful in differentiating medical illnesses that may present with depression. Mr. Z’s presentation warrants investigating these tests. His history of traumatic splenectomy and night sweats suggests an infection. The team’s initial recommendations include laboratory tests, discontinuing divalproex because it may be causing thrombocytopenia, and decreasing risperidone to 2 mg/d to improve his fatigue and possibly developed extrapyramidal symptoms.
Table 2
Potential infectious causes of chronic encephalopathy
| Type of infection | Organism/disease |
|---|---|
| Mycobacterial | Mycobacterium tuberculosis |
| Spirochetal | Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme disease), Leptospira |
| Bacterial | Brucella, Listeria, Nocardia, Actinomyces israelii, Whipple’s disease |
| Viral | HIV/AIDS, cytomegalovirus, varicella zoster virus, herpes simplex virus, enterovirus |
| Fungal | Histoplasmosis, coccidiosis, sporothrix, Blastomyces, Cryptococcus |
| Parasitic | Toxoplasmosis, taenia solium (cysticercosis), Schistosoma, Acanthamoeba |
| AIDS: acquired immunodeficiency syndrome; HIV: human immunodeficiency virus Source: Reference 8 | |
Table 3
Differentiating medical illnesses that may mimic depression
| Laboratory tests |
|
| Imaging studies |
|
| Other tests |
|
| Procedures |
|
| ABG: arterial blood gases; CBC: complete blood count; EEG: electroencephalogram; ELISA: enzyme-linked immunosorbent assay; HIV: human immunodeficiency virus; VDRL: venereal disease research laboratory Source: Reference 1 |
TREATMENT: Cause revealed
Mr. Z develops a persistent fever of 102°F with continuous profuse sweating and a hypotensive episode. Blood work reveals mild anemia, thrombocytopenia, and increased coagulation parameters with high D-dimer and low fibrinogen, consistent with diagnosis of disseminated intravascular coagulation (DIC) secondary to infectious etiology. Thyroid and HIV tests are negative. After further evaluation, Mr. Z remembers that 4 months earlier he removed several ticks from his legs after hunting; he also remembers experiencing shivering and night sweats several weeks before he was hospitalized. His blood smear is positive for babesiosis and further testing confirms positive Lyme antibodies. Mr. Z is started on aggressive hemodynamic stabilization and a pathogen-tailored course of antibiotics for several weeks. This results in improvement and discharge home in a stable condition. His depression and fatigue improve but do not fully remit by the time he is discharged.
The authors’ observations
Lyme disease is one of the fastest-growing infectious diseases in the United States.9 The prevalence of positive Lyme antibodies is 30% higher in psychiatric populations than the general population.10 Lyme disease is transmitted by deer tick bite, often undetected, that is infected with spirochete Borrelia burgdorferi. To be infectious, ticks need to be attached to the skin for 24 to 48 hours,11,12 although individual cases have reported transmission in <24 hours. The clinical manifestations of Lyme disease can be divided into 3 phases:
- early localized phase, characterized by the distinctive skin lesion erythema migrans with or without constitutional symptoms
- early disseminated phase, characterized by multiple erythema migrans lesions and neurologic and/or cardiac findings
- late or chronic disease associated with intermittent/persistent arthritis and/or neurologic problems.11,13
The clinical features of each stage frequently overlap and some patients in a later stage of Lyme disease do not have prior signs or symptoms of the disease. Because it is a multisystem disease, Lyme disease can attack the CNS in the form of neuroborreliosis, a clinical diagnosis, without involving other systems, and its neuropsychiatric manifestations can resemble neurosyphilis because both organisms are spirochetes.11,13,14 CNS disorders have been found in up to 40% of Lyme disease cases.11 In neuroborreliosis, cognitive problems usually predominate; however, neuroborreliosis can mimic multiple brain diseases presenting with various neurologic and psychiatric symptoms (Table 4)14,15 and can present at any time after the tick bite. Furthermore neuroborreliosis is difficult to diagnose because symptoms may remain dormant and emerge after several years.11,13,14Borrelia burgdorferi is challenging to isolate and grow in the lab, and enzyme-linked immunosorbent assay (ELISA) testing for antibodies is highly specific but not very sensitive,16 frequently giving false negative results. Western blot confirms the diagnosis.
Table 4
Late-stage neuropsychiatric symptoms of Lyme disease
| Cognitive problems, memory problems, forgetfulness, slowing of thought processing, dysfunction in visuospatial orientation, dyslexia |
| Depression |
| Mood swings |
| Psychosis |
| Violent behavior/irritability |
| OCD |
| Anxiety |
| Panic attacks |
| Sleep disorders |
| Seizures |
| ADHD-like symptoms |
| Autism-like behavior |
| Chronic fatigue syndrome |
| Fibromyalgia |
| ADHD: attention-deficit/hyperactivity disorder; OCD: obsessive-compulsive disorder Source: References 14,15 |
Mr. Z’s presentation also reflects co-infection with babesiosis. Babesia is malaria-like protozoa diagnosed by blood smear that can cause a fatal illness in immuno-compromised patients. The clinical picture varies from mild symptoms such as night sweats, chills, arthralgias, and anorexia with thrombocytopenia to severe and potentially fatal outcomes in immunocompromised patients, including DIC, acute renal failure, sepsis, congestive heart failure, and myocardial infarction.11 Risk factors for the severest forms of babesiosis are age >50, co-infection with Lyme disease, and splenectomy,11 all of which were present in Mr. Z. Co-infected patients experience fatigue, headache, anorexia, and emotional lability more frequently than those with Lyme disease alone.12
Treatment options
Treatment of Lyme disease/neuroborreliosis is complex. The mainstay approach is antibiotics. Despite adequate treatment, many patients experience continued impairment, including chronic pain, fatigue, and cognitive and psychiatric symptoms.11,14 There is some evidence Borrelia burgdorferi can persist and re-emerge after adequate treatment.14,17 The National Institute of Health sponsored several clinical trials of prolonged antibiotic treatment for chronic Lyme disease. Some results suggested improvement in fatigue and cognitive function, although these results were not sustained.18
There is a strong link between mental illness and increased prevalence of positive Lyme disease antibodies.10 Several studies report increased risk of infection during psychological stress that may be related to an altered immune system response.19 Evidence suggests that Borrelia burgdorferi can alter immune system response, making T cells more reactive not only to Borrelia burgdorferi antigens but also to host antigens,20 creating autoimmune inflammatory reactions that could explain chronic neuropsychiatric symptoms. It appears Lyme disease antigens can mimic certain autoantigens (for example, in the thyroid gland).21 Whether there is a role for autoimmune therapy in treating chronic symptoms needs to be investigated.
Once Lyme disease is diagnosed, educating patients and families becomes an important part of treatment because many patients report feeling stigmatized by the diagnosis. Referral to a Lyme disease support group may be beneficial. Patients with neuropsychiatric symptoms that persist after antibiotic treatment should be offered symptom-based treatment, including medications and therapy.
Related Resource
- Centers for Disease Control and Prevention. Lyme disease: Resources for clinicians. www.cdc.gov/lyme/healthcare/clinicians.html.
Drug Brand Names
- Divalproex sodium • Depakote
- Levothyroxine • Levoxyl, Synthroid
- Risperidone • Risperdal
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Discuss this article at www.facebook.com/CurrentPsychiatry
Mr. Z, age 61, is referred by his primary care clinician to the hospital’s medical service with increasing depressive symptoms and non-pruritic rash. He has a history of bipolar I disorder for >30 years. When the primary care physician evaluated Mr. Z, his vitals were normal, but blood work revealed mild anemia and thrombocytopenia of 34 x103/μL, which prompted referral to the hospital. During admission, the psychiatric consultation service is called to evaluate Mr. Z’s depressive symptoms.
Mr. Z reports having chronic sleep problems and feeling cold and tired, shivering at times, but has no pain. He says he’s worried because he feels severely depressed, worthless, and hopeless, but denies suicidal ideation and psychosis. Mr. Z says he started experiencing increasingly depressed mood, anhedonia, insomnia, fatigue, poor appetite, and concentration 2 months ago. At that time his outpatient psychiatrist started Mr. Z on risperidone, 6 mg/d, and divalproex, 1,500 mg at bedtime because of emerging mood symptoms, after he was off medication for 7 months. Mr. Z attributed his worsened mood symptoms to being overwhelmed by several psychosocial stressors, including going through a complicated divorce, financial problems, and homelessness after being evicted from his apartment.
A review of Mr. Z’s psychiatric history reveals several remote hospitalizations—the last was 7 years ago—for escalated manic symptoms after he stopped taking his medication. He denies past suicide attempts. Mr. Z says he is compliant with his current medication regimen—risperidone, 6 mg/d, and divalproex, 1,500 mg at bedtime. He denies illicit drug use and says he drinks “a couple of beers, mostly on weekends.” Family history is positive for depression and bipolar II disorder.
His medical history is significant for hypothyroidism after goiter removal 6 years ago, for which he takes levothyroxine, 150 mcg/d, and a sports injury-related splenectomy in childhood. He reports no allergies. Vital signs at the time of admission are temperature, 99.1°F; pulse, 98 beats per minute; respiration, 16 breaths per minute; blood pressure, 123/73 mm/Hg; and oxygen saturation, 97%.
During the interview, Mr. Z presents with tired facies and exhibits psychomotor retardation. He has to force himself to stay engaged in the evaluation and maintain eye contact. His speech is clear, regular, and soft. Mr. Z says he is “very depressed”; his affect is constricted, almost flat, stable, and consistent with depressed mood. His thought process is linear and somewhat concrete and his thought content is notable for hopelessness, although Mr. Z continues to deny suicidal or homicidal ideations. No hallucinations or apparent delusions are noted. Insight and judgment are fair. Mr. Z understands his current mental state; however, he displays some lack of knowledge regarding his current hospitalization. Cognition is intact.
The authors’ observations
The differential diagnosis in patients presenting with mood changes is extensive (Table 1)1 and in Mr. Z’s case includes several precipitating and perpetuating factors. Mr. Z presents with severe depressive symptoms and meets DSM-IV-TR criteria for a major depressive episode (MDE). This presentation is not typical of his bipolar I disorder because Mr. Z has never experienced an MDE and usually presents with escalating hypomanic/manic symptoms in the context of medication nonadherence. Nevertheless, Mr. Z has several risk factors for severe depression, including a family psychiatric history, multiple enduring social stressors and life crises, and medical conditions.
In the general population, the lifetime risk for developing depression is 8% to 17%.2 The risk of developing a mood disorder increases significantly if a first-degree relative is diagnosed with a mood disorder; the relative risk is 10.3 for bipolar disorder and 3.2 for depression.3 Additionally, Mr. Z is going through a complicated divorce, has financial problems, and is homeless, all of which could trigger an MDE. Furthermore, hypothyroidism shares many symptoms of depression, including fatigue, lethargy, anhedonia, cold intolerance, and low mood; mental status changes frequently are the initial presentation of thyroid problems.4 Physicians started Mr. Z on a new medication regimen (risperidone and divalproex) to control mood instability, which coincided with symptom onset. Atypical antipsychotics have been reported to precipitate depressive symptoms; their side effect profile includes extrapyramidal effects, such as flat affect, which can be mistaken for depression.5 Rapid valproate titration can mimic neurovegetative symptoms of depression and cause dose-dependent thrombocytopenia and rash, which could explain his initial presentation.6 Finally, Mr. Z’s history of traumatic splenectomy, change in mental status, and thrombocytopenia suggest an infectious etiology.
Table 1
Differential diagnosis in patients presenting with mood changes
| Cerebrovascular disease |
| Degenerative disorders (Parkinson’s disease, Huntington’s disease, Wilson’s disease) |
| Demyelinating disorders (multiple sclerosis, amyotrophic lateral sclerosis, lipid storage disease) |
| Endocrine disorders (Addison’s disease, Cushing’s disease, hyperthyroidism, hypothyroidism, hyperparathyroidism, pituitary dysfunction) |
| Epilepsy |
| Infectious diseases |
| Immune diseases |
| Metabolic encephalopathy |
| Neoplasm |
| Nutritional deficits (thiamine, niacin, vitamin B12) |
| Primary psychiatric disorders (mood disorders, dementia, sleep disorders) |
| Substance use |
| Toxins/medications |
| Traumatic brain injury |
| Source: Reference 1 |
Possible infectious causes
The increased prevalence of immune suppression due to human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or from therapeutic modalities such as cancer therapy or splenectomy has led to an increased number of chronic CNS infections, manifesting with an array of neuropsychiatric symptoms and nonspecific physiological reactions.1,7 Mr. Z complains of a 2-month period of worsening depression that could suggest an infectious process with an insidious onset. Some infectious agents that can cause chronic CNS infection and encephalopathy are presented in Table 2.8 HIV, tuberculosis, syphilis, Lyme disease, and herpes simplex virus are becoming more prevalent and can present with neuropsychiatric symptoms.1 For example, in addition to thrombocytopenia and low-grade fever, patients with HIV may exhibit a broad range of neuropsychiatric symptoms such as cognitive problems, impaired executive and motor functioning, sleep disturbance, and anxiety. These patients frequently present with low mood and neurovegetative symptoms of depression.7 Similarly, the same tick responsible for Lyme disease infection can transmit other infectious agents that can cause thrombocytopenia, including Babesia, Ehrlichia chaffeensis, Anaplasma phagocytophilum, and human Ewingii ehrlichiosis.
The authors’ observations
Diagnosis of a mood change, particularly an MDE, is clinical, based on careful psychiatric evaluation using standardized criteria rather than a specific lab test. However, some laboratory studies (Table 3)1 are useful in differentiating medical illnesses that may present with depression. Mr. Z’s presentation warrants investigating these tests. His history of traumatic splenectomy and night sweats suggests an infection. The team’s initial recommendations include laboratory tests, discontinuing divalproex because it may be causing thrombocytopenia, and decreasing risperidone to 2 mg/d to improve his fatigue and possibly developed extrapyramidal symptoms.
Table 2
Potential infectious causes of chronic encephalopathy
| Type of infection | Organism/disease |
|---|---|
| Mycobacterial | Mycobacterium tuberculosis |
| Spirochetal | Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme disease), Leptospira |
| Bacterial | Brucella, Listeria, Nocardia, Actinomyces israelii, Whipple’s disease |
| Viral | HIV/AIDS, cytomegalovirus, varicella zoster virus, herpes simplex virus, enterovirus |
| Fungal | Histoplasmosis, coccidiosis, sporothrix, Blastomyces, Cryptococcus |
| Parasitic | Toxoplasmosis, taenia solium (cysticercosis), Schistosoma, Acanthamoeba |
| AIDS: acquired immunodeficiency syndrome; HIV: human immunodeficiency virus Source: Reference 8 | |
Table 3
Differentiating medical illnesses that may mimic depression
| Laboratory tests |
|
| Imaging studies |
|
| Other tests |
|
| Procedures |
|
| ABG: arterial blood gases; CBC: complete blood count; EEG: electroencephalogram; ELISA: enzyme-linked immunosorbent assay; HIV: human immunodeficiency virus; VDRL: venereal disease research laboratory Source: Reference 1 |
TREATMENT: Cause revealed
Mr. Z develops a persistent fever of 102°F with continuous profuse sweating and a hypotensive episode. Blood work reveals mild anemia, thrombocytopenia, and increased coagulation parameters with high D-dimer and low fibrinogen, consistent with diagnosis of disseminated intravascular coagulation (DIC) secondary to infectious etiology. Thyroid and HIV tests are negative. After further evaluation, Mr. Z remembers that 4 months earlier he removed several ticks from his legs after hunting; he also remembers experiencing shivering and night sweats several weeks before he was hospitalized. His blood smear is positive for babesiosis and further testing confirms positive Lyme antibodies. Mr. Z is started on aggressive hemodynamic stabilization and a pathogen-tailored course of antibiotics for several weeks. This results in improvement and discharge home in a stable condition. His depression and fatigue improve but do not fully remit by the time he is discharged.
The authors’ observations
Lyme disease is one of the fastest-growing infectious diseases in the United States.9 The prevalence of positive Lyme antibodies is 30% higher in psychiatric populations than the general population.10 Lyme disease is transmitted by deer tick bite, often undetected, that is infected with spirochete Borrelia burgdorferi. To be infectious, ticks need to be attached to the skin for 24 to 48 hours,11,12 although individual cases have reported transmission in <24 hours. The clinical manifestations of Lyme disease can be divided into 3 phases:
- early localized phase, characterized by the distinctive skin lesion erythema migrans with or without constitutional symptoms
- early disseminated phase, characterized by multiple erythema migrans lesions and neurologic and/or cardiac findings
- late or chronic disease associated with intermittent/persistent arthritis and/or neurologic problems.11,13
The clinical features of each stage frequently overlap and some patients in a later stage of Lyme disease do not have prior signs or symptoms of the disease. Because it is a multisystem disease, Lyme disease can attack the CNS in the form of neuroborreliosis, a clinical diagnosis, without involving other systems, and its neuropsychiatric manifestations can resemble neurosyphilis because both organisms are spirochetes.11,13,14 CNS disorders have been found in up to 40% of Lyme disease cases.11 In neuroborreliosis, cognitive problems usually predominate; however, neuroborreliosis can mimic multiple brain diseases presenting with various neurologic and psychiatric symptoms (Table 4)14,15 and can present at any time after the tick bite. Furthermore neuroborreliosis is difficult to diagnose because symptoms may remain dormant and emerge after several years.11,13,14Borrelia burgdorferi is challenging to isolate and grow in the lab, and enzyme-linked immunosorbent assay (ELISA) testing for antibodies is highly specific but not very sensitive,16 frequently giving false negative results. Western blot confirms the diagnosis.
Table 4
Late-stage neuropsychiatric symptoms of Lyme disease
| Cognitive problems, memory problems, forgetfulness, slowing of thought processing, dysfunction in visuospatial orientation, dyslexia |
| Depression |
| Mood swings |
| Psychosis |
| Violent behavior/irritability |
| OCD |
| Anxiety |
| Panic attacks |
| Sleep disorders |
| Seizures |
| ADHD-like symptoms |
| Autism-like behavior |
| Chronic fatigue syndrome |
| Fibromyalgia |
| ADHD: attention-deficit/hyperactivity disorder; OCD: obsessive-compulsive disorder Source: References 14,15 |
Mr. Z’s presentation also reflects co-infection with babesiosis. Babesia is malaria-like protozoa diagnosed by blood smear that can cause a fatal illness in immuno-compromised patients. The clinical picture varies from mild symptoms such as night sweats, chills, arthralgias, and anorexia with thrombocytopenia to severe and potentially fatal outcomes in immunocompromised patients, including DIC, acute renal failure, sepsis, congestive heart failure, and myocardial infarction.11 Risk factors for the severest forms of babesiosis are age >50, co-infection with Lyme disease, and splenectomy,11 all of which were present in Mr. Z. Co-infected patients experience fatigue, headache, anorexia, and emotional lability more frequently than those with Lyme disease alone.12
Treatment options
Treatment of Lyme disease/neuroborreliosis is complex. The mainstay approach is antibiotics. Despite adequate treatment, many patients experience continued impairment, including chronic pain, fatigue, and cognitive and psychiatric symptoms.11,14 There is some evidence Borrelia burgdorferi can persist and re-emerge after adequate treatment.14,17 The National Institute of Health sponsored several clinical trials of prolonged antibiotic treatment for chronic Lyme disease. Some results suggested improvement in fatigue and cognitive function, although these results were not sustained.18
There is a strong link between mental illness and increased prevalence of positive Lyme disease antibodies.10 Several studies report increased risk of infection during psychological stress that may be related to an altered immune system response.19 Evidence suggests that Borrelia burgdorferi can alter immune system response, making T cells more reactive not only to Borrelia burgdorferi antigens but also to host antigens,20 creating autoimmune inflammatory reactions that could explain chronic neuropsychiatric symptoms. It appears Lyme disease antigens can mimic certain autoantigens (for example, in the thyroid gland).21 Whether there is a role for autoimmune therapy in treating chronic symptoms needs to be investigated.
Once Lyme disease is diagnosed, educating patients and families becomes an important part of treatment because many patients report feeling stigmatized by the diagnosis. Referral to a Lyme disease support group may be beneficial. Patients with neuropsychiatric symptoms that persist after antibiotic treatment should be offered symptom-based treatment, including medications and therapy.
Related Resource
- Centers for Disease Control and Prevention. Lyme disease: Resources for clinicians. www.cdc.gov/lyme/healthcare/clinicians.html.
Drug Brand Names
- Divalproex sodium • Depakote
- Levothyroxine • Levoxyl, Synthroid
- Risperidone • Risperdal
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Stern TA, Rosenbaum JF, Fava M, et al. eds. Massachusetts General Hospital comprehensive clinical psychiatry. Philadelphia, PA: Mosby; 2008;257-277.
2. Andrade L, Caraveo-Anduaga JJ, Berglund P, et al. The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res. 2003;12(1):3-21.
3. Merikangas KR, Low NC. The epidemiology of mood disorders. Curr Psychiatry Rep. 2004;6:411-421.
4. Brown GM. Psychiatric and neurologic aspects of endocrine disease. In Krieger DT Hughes JC, eds. Neuroendocrinology. Sunderland, MA: Sinauer Associates; 1980;185-194.
5. Maguire GA. Comprehensive understanding of schizophrenia and its treatment. Am J Health Syst Pharm. 2002;59(17 suppl 5):S4-S11.
6. Dreifuss FE, Langer DH. Side effects of valproate. Am J Med. 1988;84(1A):34-41.
7. Perry S, Jacobsen P. Neuropsychiatric manifestations of AIDS-spectrum disorders. Hosp Community Psychiatry. 1986;37:135-142.
8. Hildebrand J, Aoun M. Chronic meningitis: still a diagnostic challenge. J Neurol. 2003;250(6):653-660.
9. Bacon RM, Kugeler KJ, Mead PS. Centers for Disease Control and Prevention (CDC). Surveillance for Lyme disease—United States 1992-2006. MMWR Surveill Summ. 2008;57(10):1-9.
10. Hájek T, Pasková B, Janovská D, et al. Higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients than in healthy subjects. Am J Psychiatry. 2002;159:297-301.
11. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.
12. Krause PJ, Telford SR 3rd, Spielman A, et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. 1996;275(21):1657-1660.
13. Hildenbrand P, Craven DE, Jones R, et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol. 2009;30:1079-1087.
14. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151:1571-1583.
15. Fallon BA, Nields JA, Burrascano JJ, et al. The neuropsychiatric manifestations of Lyme borreliosis. Psychiatr Q. 1992;63(1):95-117.
16. Stricker RB, Johnson L. Lyme wars: let’s tackle the testing. BMJ. 2007;335:1008.-
17. Hodzic E, Feng S, Holden K, et al. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52(5):1728-1736.
18. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.
19. Sheridan JF, Dobbs C, Brown D, et al. Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection. Clin Microbiol Rev. 1994;7(2):200-212.
20. Yssel H, Shanafelt MC, Soderberg C, et al. Borrelia burgdorferi activates a T helper 1-like T cell subset in Lyme arthritis. J Exp Med. 1991;174:593-601.
21. Benvenga S, Guarneri F, Vaccaro M, et al. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid. 2004;14(11):964-966.
1. Stern TA, Rosenbaum JF, Fava M, et al. eds. Massachusetts General Hospital comprehensive clinical psychiatry. Philadelphia, PA: Mosby; 2008;257-277.
2. Andrade L, Caraveo-Anduaga JJ, Berglund P, et al. The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res. 2003;12(1):3-21.
3. Merikangas KR, Low NC. The epidemiology of mood disorders. Curr Psychiatry Rep. 2004;6:411-421.
4. Brown GM. Psychiatric and neurologic aspects of endocrine disease. In Krieger DT Hughes JC, eds. Neuroendocrinology. Sunderland, MA: Sinauer Associates; 1980;185-194.
5. Maguire GA. Comprehensive understanding of schizophrenia and its treatment. Am J Health Syst Pharm. 2002;59(17 suppl 5):S4-S11.
6. Dreifuss FE, Langer DH. Side effects of valproate. Am J Med. 1988;84(1A):34-41.
7. Perry S, Jacobsen P. Neuropsychiatric manifestations of AIDS-spectrum disorders. Hosp Community Psychiatry. 1986;37:135-142.
8. Hildebrand J, Aoun M. Chronic meningitis: still a diagnostic challenge. J Neurol. 2003;250(6):653-660.
9. Bacon RM, Kugeler KJ, Mead PS. Centers for Disease Control and Prevention (CDC). Surveillance for Lyme disease—United States 1992-2006. MMWR Surveill Summ. 2008;57(10):1-9.
10. Hájek T, Pasková B, Janovská D, et al. Higher prevalence of antibodies to Borrelia burgdorferi in psychiatric patients than in healthy subjects. Am J Psychiatry. 2002;159:297-301.
11. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.
12. Krause PJ, Telford SR 3rd, Spielman A, et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. 1996;275(21):1657-1660.
13. Hildenbrand P, Craven DE, Jones R, et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol. 2009;30:1079-1087.
14. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151:1571-1583.
15. Fallon BA, Nields JA, Burrascano JJ, et al. The neuropsychiatric manifestations of Lyme borreliosis. Psychiatr Q. 1992;63(1):95-117.
16. Stricker RB, Johnson L. Lyme wars: let’s tackle the testing. BMJ. 2007;335:1008.-
17. Hodzic E, Feng S, Holden K, et al. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008;52(5):1728-1736.
18. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.
19. Sheridan JF, Dobbs C, Brown D, et al. Psychoneuroimmunology: stress effects on pathogenesis and immunity during infection. Clin Microbiol Rev. 1994;7(2):200-212.
20. Yssel H, Shanafelt MC, Soderberg C, et al. Borrelia burgdorferi activates a T helper 1-like T cell subset in Lyme arthritis. J Exp Med. 1991;174:593-601.
21. Benvenga S, Guarneri F, Vaccaro M, et al. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid. 2004;14(11):964-966.
Beyond lithium: Using psychotherapy to reduce suicide risk in bipolar disorder
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Patients with bipolar disorder (BD) have a high risk for suicidal ideation, suicide attempts, and suicide.1-3 Approximately 25% to 50% of BD patients attempt suicide at least once, and their attempts often are lethal—the ratio of attempts to completed suicides in BD patients is 3:1, compared with 30:1 in the general population.4 Lithium has been shown to effectively stabilize BD patients’ mood and significantly reduce the rates of suicide attempts and completed suicides,5-9 but does not reduce BD patients’ long-term suicide risk to that of the general population.
Literature on psychotherapeutic treatments for patients with BD primarily focuses on improving patients’ adherence to pharmacotherapy and achieving faster recovery and remission.10 Nonpharmacologic treatments for patients with BD include psychoeducation, family-focused psychoeducation, cognitive therapy, and interpersonal and social rhythm therapy (Table 1).11 Literature on nonpharmacologic treatments to address suicidality in BD patients is limited,12,13 and additional psychotherapeutic interventions to reduce suicide risk in BD patients are needed.14
In this article, I describe a novel psychotherapeutic intervention I use that integrates cognitive therapy principles with ideas derived from the psychosynthesis model.15,16 It consists of teaching patients to “disidentify” from suicidal thoughts, followed by a guided-imagery exercise in which patients experience a future positive life event with all 5 senses and internalize this experience. This creates a “hook into the future” that changes the present to match the future event and acts as an antidote to suicidal thoughts. I have used this strategy successfully in many patients as an adjunct to pharmacotherapy.
Table 1
Nonpharmacologic interventions for bipolar disorder
| Goals | Techniques |
|---|---|
| Psychoeducation | |
|
|
| Family-focused psychoeducation | |
|
|
| Cognitive therapy | |
|
|
| Interpersonal and social rhythm therapy | |
|
|
| BD: bipolar disorder Source: Reference 11 | |
A theoretical model
Roberto Assagioli, who established the approach to psychology called psychosynthesis, formulated a fundamental psychological principle in controlling one’s behavior: “We are dominated by everything with which our self becomes identified. We can dominate and control everything from which we disidentify ourselves.”15 According to the psychosynthesis model, it is easier to change thoughts we identify as foreign to “the self” (ego-dystonic) than thoughts we identify as being part of “the self” (ego-syntonic).
Patients whose suicidal thoughts are ego-syntonic identify with the thoughts as representing themselves and take ownership of these thoughts. Such patients are at a greater risk of acting on suicidal thoughts.
Patients whose suicidal thoughts are ego-dystonic consider the suicidal thoughts foreign to their core self and do not believe such thoughts represent them. In essence, they “disown” the thoughts and typically want to control and eliminate them. Examples of patients’ ego-syntonic vs ego-dystonic suicidal thoughts are listed in Table 2.
This construct calls for an intervention to help patients who have ego-syntonic suicidal thoughts restructure them as a manifestation of BD, rather then the patient’s core self belief. The intervention emphasizes the patient is not “a suicidal patient” but suffers from an illness that may manifest with suicidal ideation. Many BD patients overly identify with their disease, stating, “I am bipolar” or “I am suicidal.” The “I am” statement originates from the verb “to be,” which implies the disease is part of the patient’s identity. The goal of this intervention is to help the patient learn to disidentify from the disease and decide that suicidal thoughts do not represent their core self, but are a manifestation of the underlying disease.
The psychosynthesis model of helping patients disidentify and therefore disown suicidal thoughts is compatible with interventions that use mindfulness-based cognitive therapy training to teach patients to experience their thoughts as just passing through their consciousness without taking ownership of them.17
Table 2
Examples of ego-syntonic vs ego-dystonic suicidal thoughts
| Ego-syntonic | Ego-dystonic |
|---|---|
| ‘I want to be dead. I found a simple and sure way to do it’ | ‘I am having suicidal thoughts again and I don’t like it’ |
| ‘I know my family will be better off without me’ | ‘I’m afraid the illness is coming back. I can’t stop these images’ |
| ‘Life is too hard, too much pain. I just want to end it all’ | ‘I see my body in a coffin. It scares the hell out of me’ |
| ‘I’ve come to the end, life for me is over and done’ | ‘I don’t want to die. Please help me get well again’ |
| ‘I know my life is over. I just have to find the right way to do it’ | ‘It is as if a part of me wants to die but the rest of me wants to live’ |
| ‘Nobody cares about me. It is as if I am already dead’ | ‘I know my family needs me. I want to be there for them’ |
| ‘I have nothing to live for’ | ‘I have so much to live for, why am I having such crazy thoughts?’ |
The intervention
Assessment of suicidality is a fundamental skill for every mental health clinician.18 The psychotherapeutic intervention I use integrates the cognitive therapy principles of reframing, relabeling, and restructuring patients’ thoughts with disidentification from dysfunctional thoughts, feelings, and desires, based on psychosynthesis principles.
First, I conduct a comprehensive mental status examination that includes an in-depth exploration of the patient’s suicidal thoughts to determine if they are ego-syntonic or ego-dystonic. I begin by asking patients to clarify and elaborate on their statements referring to suicide, asking questions such as “Is there a part of you that objects to these thoughts?” and “Is there a part of you that wants to live?” If a patient indicates that he or she does experience inner conflict regarding such thoughts, these thoughts are classified as ego-dystonic. If a patient does not have any counter thoughts regarding the suicidal thoughts and fully identifies with them, the thoughts are classified as ego-syntonic.
I follow this with a treatment plan that helps patients change their view of their suicidal thoughts. I ask the patient to change these suicidal thoughts to ego-dystonic by focusing on the following statement: “I, (patient’s name), am a human being and like all human beings, I have thoughts; however, I am not my thoughts, I am much more than that.” I ask my patient to read this out loud and to mindfully meditate on this statement several times a day to reinforce the new understanding that these suicidal thoughts are a manifestation of the chemical imbalance of the mood disorder, and do not represent the patient as a person.
This intervention is paired with a future-focused internalized imagery experience I have described in previous articles.19,20 In this part of the treatment, the patient and I discuss a specific expected life milestone that is positive and for which he or she would want to be present (eg, children graduating from high school or college, a wedding, birth of a child/grandchild, etc.). Using guided imagery, the patient experiences this event with all 5 senses during the session. I instruct the patient to internalize the experience and bring it back from the future to the present. This creates a “hook into the future” that is coupled with this desired milestone event in the patient’s life.
The following 3 case studies provide examples of the application of this treatment intervention.
CASE 1: Disidentifying family history
Mrs. G, a 42-year-old mother of 2, suffers from bipolar II disorder with recurrent episodes of depression associated with ego-syntonic suicidal thoughts. She states that at times she feels she is a burden to her husband and children and believes they may be better off without her. She says she believes “ending it all” must be her destiny. After further investigation, I learn Mrs. G has a family history of BD and 3 relatives have committed suicide. This family history may partially explain her belief that suicide must be “in her genes.”
I discuss with Mrs. G the strategy of changing her thoughts. I tell her to write in her journal—which she brings to her sessions—the following statements: “I am a human being. I am an adult woman and mother of 2 children. I know I have thoughts but I am not my thoughts, I am much more than that. I know I have genes but I am not my genes, I am much more than that. I know I have feelings, but I am not my feelings, I am much more than that. I know I have cousins, uncles, aunts, and other relatives but I am not my relatives. I am uniquely myself, different from the others.”
I ask Mrs. G to read these statements out loud and repeat them several times a day to reinforce this new way of perceiving the suicidal thoughts and to disidentify from the thoughts and her family history as it relates to suicide.
Mrs. G and I talk about the future and expected family milestones. When I ask if her son would want her to be present at his college graduation, she says yes. We then discuss in detail the date, time of day, and location of this event, followed by a guided imagery exercise focused on the graduation. She is guided to experience this event with all 5 senses and describes the event in detail, including the expression on the faces of her husband and children, their voices, and the scent of their aftershave lotion. She hears her son saying, “Mom, I love you. Thank you for being there with me all these years. I could not have done it without you.” I ask Mrs. G to internalize these experiences and carve them into her memory. She is instructed to come back from this future-focused guided imagery experience. When her eyes open, she looks at me and describes her experience in great detail, at times using the past tense, which confirms that the future-focused event was internalized.
In her next session, Mrs. G reports an improvement in her sleep and a change in her suicidal thoughts, which now are only fleeting.
CASE 2: Experiencing graduation
Ms. J, age 17, was diagnosed with bipolar I disorder when she was 15. She has a family history of BD in her mother, 2 maternal aunts, her grandmother, and an older sister. All these women have a history of suicidal thoughts and suicide attempts requiring hospital treatment, but no completed suicides.
Ms. J has been taking an adequate combination of mood stabilizers. She has recovered from 2 previous depressive episodes and is experiencing a third relapse with suicidal thoughts. At times, she experiences these thoughts as ego-syntonic; at other times, they are ego-dystonic.
I first educate her about the nature of BD, explaining that her suicidal thoughts are a manifestation of a chemical imbalance in her brain as a result of the depressive relapse. I teach her to use guided imagery to focus on her favorite place of peace and serenity, the beach, which produces immediate relief of the intense anxiety she felt.
After we complete the disidentification exercise, I ask her to focus on her high school graduation ceremony, which is scheduled to take place in 1 year. In a state of guided imagery, she experiences her graduation from high school with all 5 senses. As she returns to a state of full alertness with her eyes open, she describes the graduation ceremony experience in detail using the past tense, as if it had already occurred, thereby creating her own hook into the future. I instruct her to write about this experience in her journal and bring it with her to the next session.
The following session, Ms. J reports that her suicide ideations have “disappeared.” She says this was accompanied by improvements in her overall mood and sleep.
CASE 3: Internalizing the future
Mr. C, a 38-year-old married father of 4 children, has bipolar II disorder and is in a depressed state. He has been treated with optimal doses of mood stabilizers and atypical antipsychotics but continues to have suicidal thoughts. These thoughts are at times ego-syntonic; he says, “My family would be better off without me.” When Mr. C’s mood improves, however, the suicidal thoughts become more ego-dystonic; he expresses fear that he might act out on the thoughts and states that he does not want to die, he really wants to live and get better. He has no history of suicide attempts.
During our session, I ask Mr. C to focus on a new perspective to understand his thoughts by repeating the following statements: “I, JC, am a human being. I know I have a bipolar mood disorder; however, I must remember I am not bipolar. I have suicidal thoughts; however, I am not my thoughts, I am much more than that. I know I want to live, to heal, and to get better. I want to be alive and well so I can see and participate in my children’s graduation from high school and be there when they get married and when my grandchildren are born.”
I teach Mr. C to use guided imagery, during which he experiences such future positive images and milestones in his life in all 5 senses and internalizes them by using the “back from the future” technique.17 By the end of the session, he reports feeling better, more hopeful, and confident in his abilities to control his suicidal thoughts. I instruct him to write in his diary about his experiences with the future-focused positive milestones and to bring this assignment to his next appointment.
At his next appointment, Mr. C reports that his suicidal thoughts have become more fleeting, lasting for 10 to 30 seconds, and then spontaneously change to focus on issues of the “here and now.” When I ask him to read what he’s written, what stands out is the use of past tense verbs to describe future-focused experiences. For me, this confirms that Mr. C has internalized the future, creating the desirable “future hook” that acts as an antidote to the suicidal thoughts.
Related Resources
- Rouget BW, Aubry JM. Efficacy of psychoeducational approaches on bipolar disorders: a review of the literature. J Affect Disord. 2007;98:11-27.
- Weinberg I, Ronningstam E, Goldblatt MJ, et al. Strategies in treatment of suicidality: identification of common and treatment-specific interventions in empirically supported treatment manuals. J Clin Psychiatry. 2010;71:699-706.
Drug Brand Name
- Lithium • Eskalith, Lithobid
Disclosure
Dr. Torem reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. McIntyre RS, Konarski JZ. Bipolar disorder: a national health concern. CNS Spectr. 2004;9(11 suppl 12):6-15.
2. Tsai SY, Lee CH, Kuo CJ, et al. A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry. 2005;66(12):1586-1591.
3. Osby U, Brandt L, Correia N, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58(9):844-850.
4. Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: risks and management. CNS Spectr. 2006;11(6):465-471.
5. Gelenberg AJ. Can lithium help to prevent suicide? Acta Psychiatr Scand. 2001;104(3):161-162.
6. Schou M. Suicidal behavior and prophylactic lithium treatment of major mood disorders: a review of reviews. Suicide Life Threat Behav. 2001;30(3):289-293.
7. Burgess S, Geddes J, Hawton K, et al. Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev. 2001;(3):CD003013.-
8. Baldessarini RJ, Tondo L, Davis P, et al. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006;8(5 Pt 2):625-639.
9. Tondo L, Baldessarini RJ. Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients. Epidemiol Psichiatr Soc. 2009;18(3):179-183.
10. Miklowitz DJ. Adjunctive psychotherapy for bipolar disorder: state of the evidence. Am J Psychiatry. 2008;165(11):1408-1419.
11. Hirschfeld RMA, Harris TH, Davis HK. Making efficacious choices: the integration of pharmacotherapy and nonpharmacologic approaches to the treatment of patients with bipolar disorder. Current Psychiatry. 2009;8(10 suppl):S6-S11.
12. Rucci P, Frank E, Kostelnik B, et al. Suicide attempts in patients with bipolar I disorder during acute and maintenance phases of intensive treatment with pharmacotherapy and adjunctive psychotherapy. Am J Psychiatry. 2002;159(7):1160-1164.
13. Fountoulakis KN, Gonda X, Siamouli M, et al. Psychotherapeutic intervention and suicide risk reduction in bipolar disorder: a review of the evidence. J Affect Disord. 2009;113(1-2):21-29.
14. Pompili M, Rihmer Z, Innamorati M, et al. Assessment and treatment of suicide risk in bipolar disorders. Expert Rev Neurother. 2009;9(1):109-136.
15. Assagioli R. Psychosynthesis: a collection of basic writings. New York NY: The Viking Press Inc.; 1965.
16. Assagioli R. The act of will. New York NY: The Viking Press Inc.; 1973.
17. Williams JM, Alatiq Y, Crane C, et al. Mindfulness-based cognitive therapy (MBCT) in bipolar disorder: preliminary evaluation of immediate effects on between-episode functioning. J Affect Disord. 2008;107(1-3):275-279.
18. Shea SC. The delicate art of eliciting suicidal ideation. Psychiatric Annals. 2004;34:385-400.
19. Torem MS. “Back from the future”: a powerful age-progression technique. Am J Clin Hypn. 1992;35(2):81-88.
20. Torem MS. Treating depression: a remedy from the future. In: Yapko MD ed. Hypnosis and treating depression: applications in clinical practice. New York, NY: Routledge; 2006:97–119.
Discuss this article at www.facebook.com/CurrentPsychiatry
Patients with bipolar disorder (BD) have a high risk for suicidal ideation, suicide attempts, and suicide.1-3 Approximately 25% to 50% of BD patients attempt suicide at least once, and their attempts often are lethal—the ratio of attempts to completed suicides in BD patients is 3:1, compared with 30:1 in the general population.4 Lithium has been shown to effectively stabilize BD patients’ mood and significantly reduce the rates of suicide attempts and completed suicides,5-9 but does not reduce BD patients’ long-term suicide risk to that of the general population.
Literature on psychotherapeutic treatments for patients with BD primarily focuses on improving patients’ adherence to pharmacotherapy and achieving faster recovery and remission.10 Nonpharmacologic treatments for patients with BD include psychoeducation, family-focused psychoeducation, cognitive therapy, and interpersonal and social rhythm therapy (Table 1).11 Literature on nonpharmacologic treatments to address suicidality in BD patients is limited,12,13 and additional psychotherapeutic interventions to reduce suicide risk in BD patients are needed.14
In this article, I describe a novel psychotherapeutic intervention I use that integrates cognitive therapy principles with ideas derived from the psychosynthesis model.15,16 It consists of teaching patients to “disidentify” from suicidal thoughts, followed by a guided-imagery exercise in which patients experience a future positive life event with all 5 senses and internalize this experience. This creates a “hook into the future” that changes the present to match the future event and acts as an antidote to suicidal thoughts. I have used this strategy successfully in many patients as an adjunct to pharmacotherapy.
Table 1
Nonpharmacologic interventions for bipolar disorder
| Goals | Techniques |
|---|---|
| Psychoeducation | |
|
|
| Family-focused psychoeducation | |
|
|
| Cognitive therapy | |
|
|
| Interpersonal and social rhythm therapy | |
|
|
| BD: bipolar disorder Source: Reference 11 | |
A theoretical model
Roberto Assagioli, who established the approach to psychology called psychosynthesis, formulated a fundamental psychological principle in controlling one’s behavior: “We are dominated by everything with which our self becomes identified. We can dominate and control everything from which we disidentify ourselves.”15 According to the psychosynthesis model, it is easier to change thoughts we identify as foreign to “the self” (ego-dystonic) than thoughts we identify as being part of “the self” (ego-syntonic).
Patients whose suicidal thoughts are ego-syntonic identify with the thoughts as representing themselves and take ownership of these thoughts. Such patients are at a greater risk of acting on suicidal thoughts.
Patients whose suicidal thoughts are ego-dystonic consider the suicidal thoughts foreign to their core self and do not believe such thoughts represent them. In essence, they “disown” the thoughts and typically want to control and eliminate them. Examples of patients’ ego-syntonic vs ego-dystonic suicidal thoughts are listed in Table 2.
This construct calls for an intervention to help patients who have ego-syntonic suicidal thoughts restructure them as a manifestation of BD, rather then the patient’s core self belief. The intervention emphasizes the patient is not “a suicidal patient” but suffers from an illness that may manifest with suicidal ideation. Many BD patients overly identify with their disease, stating, “I am bipolar” or “I am suicidal.” The “I am” statement originates from the verb “to be,” which implies the disease is part of the patient’s identity. The goal of this intervention is to help the patient learn to disidentify from the disease and decide that suicidal thoughts do not represent their core self, but are a manifestation of the underlying disease.
The psychosynthesis model of helping patients disidentify and therefore disown suicidal thoughts is compatible with interventions that use mindfulness-based cognitive therapy training to teach patients to experience their thoughts as just passing through their consciousness without taking ownership of them.17
Table 2
Examples of ego-syntonic vs ego-dystonic suicidal thoughts
| Ego-syntonic | Ego-dystonic |
|---|---|
| ‘I want to be dead. I found a simple and sure way to do it’ | ‘I am having suicidal thoughts again and I don’t like it’ |
| ‘I know my family will be better off without me’ | ‘I’m afraid the illness is coming back. I can’t stop these images’ |
| ‘Life is too hard, too much pain. I just want to end it all’ | ‘I see my body in a coffin. It scares the hell out of me’ |
| ‘I’ve come to the end, life for me is over and done’ | ‘I don’t want to die. Please help me get well again’ |
| ‘I know my life is over. I just have to find the right way to do it’ | ‘It is as if a part of me wants to die but the rest of me wants to live’ |
| ‘Nobody cares about me. It is as if I am already dead’ | ‘I know my family needs me. I want to be there for them’ |
| ‘I have nothing to live for’ | ‘I have so much to live for, why am I having such crazy thoughts?’ |
The intervention
Assessment of suicidality is a fundamental skill for every mental health clinician.18 The psychotherapeutic intervention I use integrates the cognitive therapy principles of reframing, relabeling, and restructuring patients’ thoughts with disidentification from dysfunctional thoughts, feelings, and desires, based on psychosynthesis principles.
First, I conduct a comprehensive mental status examination that includes an in-depth exploration of the patient’s suicidal thoughts to determine if they are ego-syntonic or ego-dystonic. I begin by asking patients to clarify and elaborate on their statements referring to suicide, asking questions such as “Is there a part of you that objects to these thoughts?” and “Is there a part of you that wants to live?” If a patient indicates that he or she does experience inner conflict regarding such thoughts, these thoughts are classified as ego-dystonic. If a patient does not have any counter thoughts regarding the suicidal thoughts and fully identifies with them, the thoughts are classified as ego-syntonic.
I follow this with a treatment plan that helps patients change their view of their suicidal thoughts. I ask the patient to change these suicidal thoughts to ego-dystonic by focusing on the following statement: “I, (patient’s name), am a human being and like all human beings, I have thoughts; however, I am not my thoughts, I am much more than that.” I ask my patient to read this out loud and to mindfully meditate on this statement several times a day to reinforce the new understanding that these suicidal thoughts are a manifestation of the chemical imbalance of the mood disorder, and do not represent the patient as a person.
This intervention is paired with a future-focused internalized imagery experience I have described in previous articles.19,20 In this part of the treatment, the patient and I discuss a specific expected life milestone that is positive and for which he or she would want to be present (eg, children graduating from high school or college, a wedding, birth of a child/grandchild, etc.). Using guided imagery, the patient experiences this event with all 5 senses during the session. I instruct the patient to internalize the experience and bring it back from the future to the present. This creates a “hook into the future” that is coupled with this desired milestone event in the patient’s life.
The following 3 case studies provide examples of the application of this treatment intervention.
CASE 1: Disidentifying family history
Mrs. G, a 42-year-old mother of 2, suffers from bipolar II disorder with recurrent episodes of depression associated with ego-syntonic suicidal thoughts. She states that at times she feels she is a burden to her husband and children and believes they may be better off without her. She says she believes “ending it all” must be her destiny. After further investigation, I learn Mrs. G has a family history of BD and 3 relatives have committed suicide. This family history may partially explain her belief that suicide must be “in her genes.”
I discuss with Mrs. G the strategy of changing her thoughts. I tell her to write in her journal—which she brings to her sessions—the following statements: “I am a human being. I am an adult woman and mother of 2 children. I know I have thoughts but I am not my thoughts, I am much more than that. I know I have genes but I am not my genes, I am much more than that. I know I have feelings, but I am not my feelings, I am much more than that. I know I have cousins, uncles, aunts, and other relatives but I am not my relatives. I am uniquely myself, different from the others.”
I ask Mrs. G to read these statements out loud and repeat them several times a day to reinforce this new way of perceiving the suicidal thoughts and to disidentify from the thoughts and her family history as it relates to suicide.
Mrs. G and I talk about the future and expected family milestones. When I ask if her son would want her to be present at his college graduation, she says yes. We then discuss in detail the date, time of day, and location of this event, followed by a guided imagery exercise focused on the graduation. She is guided to experience this event with all 5 senses and describes the event in detail, including the expression on the faces of her husband and children, their voices, and the scent of their aftershave lotion. She hears her son saying, “Mom, I love you. Thank you for being there with me all these years. I could not have done it without you.” I ask Mrs. G to internalize these experiences and carve them into her memory. She is instructed to come back from this future-focused guided imagery experience. When her eyes open, she looks at me and describes her experience in great detail, at times using the past tense, which confirms that the future-focused event was internalized.
In her next session, Mrs. G reports an improvement in her sleep and a change in her suicidal thoughts, which now are only fleeting.
CASE 2: Experiencing graduation
Ms. J, age 17, was diagnosed with bipolar I disorder when she was 15. She has a family history of BD in her mother, 2 maternal aunts, her grandmother, and an older sister. All these women have a history of suicidal thoughts and suicide attempts requiring hospital treatment, but no completed suicides.
Ms. J has been taking an adequate combination of mood stabilizers. She has recovered from 2 previous depressive episodes and is experiencing a third relapse with suicidal thoughts. At times, she experiences these thoughts as ego-syntonic; at other times, they are ego-dystonic.
I first educate her about the nature of BD, explaining that her suicidal thoughts are a manifestation of a chemical imbalance in her brain as a result of the depressive relapse. I teach her to use guided imagery to focus on her favorite place of peace and serenity, the beach, which produces immediate relief of the intense anxiety she felt.
After we complete the disidentification exercise, I ask her to focus on her high school graduation ceremony, which is scheduled to take place in 1 year. In a state of guided imagery, she experiences her graduation from high school with all 5 senses. As she returns to a state of full alertness with her eyes open, she describes the graduation ceremony experience in detail using the past tense, as if it had already occurred, thereby creating her own hook into the future. I instruct her to write about this experience in her journal and bring it with her to the next session.
The following session, Ms. J reports that her suicide ideations have “disappeared.” She says this was accompanied by improvements in her overall mood and sleep.
CASE 3: Internalizing the future
Mr. C, a 38-year-old married father of 4 children, has bipolar II disorder and is in a depressed state. He has been treated with optimal doses of mood stabilizers and atypical antipsychotics but continues to have suicidal thoughts. These thoughts are at times ego-syntonic; he says, “My family would be better off without me.” When Mr. C’s mood improves, however, the suicidal thoughts become more ego-dystonic; he expresses fear that he might act out on the thoughts and states that he does not want to die, he really wants to live and get better. He has no history of suicide attempts.
During our session, I ask Mr. C to focus on a new perspective to understand his thoughts by repeating the following statements: “I, JC, am a human being. I know I have a bipolar mood disorder; however, I must remember I am not bipolar. I have suicidal thoughts; however, I am not my thoughts, I am much more than that. I know I want to live, to heal, and to get better. I want to be alive and well so I can see and participate in my children’s graduation from high school and be there when they get married and when my grandchildren are born.”
I teach Mr. C to use guided imagery, during which he experiences such future positive images and milestones in his life in all 5 senses and internalizes them by using the “back from the future” technique.17 By the end of the session, he reports feeling better, more hopeful, and confident in his abilities to control his suicidal thoughts. I instruct him to write in his diary about his experiences with the future-focused positive milestones and to bring this assignment to his next appointment.
At his next appointment, Mr. C reports that his suicidal thoughts have become more fleeting, lasting for 10 to 30 seconds, and then spontaneously change to focus on issues of the “here and now.” When I ask him to read what he’s written, what stands out is the use of past tense verbs to describe future-focused experiences. For me, this confirms that Mr. C has internalized the future, creating the desirable “future hook” that acts as an antidote to the suicidal thoughts.
Related Resources
- Rouget BW, Aubry JM. Efficacy of psychoeducational approaches on bipolar disorders: a review of the literature. J Affect Disord. 2007;98:11-27.
- Weinberg I, Ronningstam E, Goldblatt MJ, et al. Strategies in treatment of suicidality: identification of common and treatment-specific interventions in empirically supported treatment manuals. J Clin Psychiatry. 2010;71:699-706.
Drug Brand Name
- Lithium • Eskalith, Lithobid
Disclosure
Dr. Torem reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Discuss this article at www.facebook.com/CurrentPsychiatry
Patients with bipolar disorder (BD) have a high risk for suicidal ideation, suicide attempts, and suicide.1-3 Approximately 25% to 50% of BD patients attempt suicide at least once, and their attempts often are lethal—the ratio of attempts to completed suicides in BD patients is 3:1, compared with 30:1 in the general population.4 Lithium has been shown to effectively stabilize BD patients’ mood and significantly reduce the rates of suicide attempts and completed suicides,5-9 but does not reduce BD patients’ long-term suicide risk to that of the general population.
Literature on psychotherapeutic treatments for patients with BD primarily focuses on improving patients’ adherence to pharmacotherapy and achieving faster recovery and remission.10 Nonpharmacologic treatments for patients with BD include psychoeducation, family-focused psychoeducation, cognitive therapy, and interpersonal and social rhythm therapy (Table 1).11 Literature on nonpharmacologic treatments to address suicidality in BD patients is limited,12,13 and additional psychotherapeutic interventions to reduce suicide risk in BD patients are needed.14
In this article, I describe a novel psychotherapeutic intervention I use that integrates cognitive therapy principles with ideas derived from the psychosynthesis model.15,16 It consists of teaching patients to “disidentify” from suicidal thoughts, followed by a guided-imagery exercise in which patients experience a future positive life event with all 5 senses and internalize this experience. This creates a “hook into the future” that changes the present to match the future event and acts as an antidote to suicidal thoughts. I have used this strategy successfully in many patients as an adjunct to pharmacotherapy.
Table 1
Nonpharmacologic interventions for bipolar disorder
| Goals | Techniques |
|---|---|
| Psychoeducation | |
|
|
| Family-focused psychoeducation | |
|
|
| Cognitive therapy | |
|
|
| Interpersonal and social rhythm therapy | |
|
|
| BD: bipolar disorder Source: Reference 11 | |
A theoretical model
Roberto Assagioli, who established the approach to psychology called psychosynthesis, formulated a fundamental psychological principle in controlling one’s behavior: “We are dominated by everything with which our self becomes identified. We can dominate and control everything from which we disidentify ourselves.”15 According to the psychosynthesis model, it is easier to change thoughts we identify as foreign to “the self” (ego-dystonic) than thoughts we identify as being part of “the self” (ego-syntonic).
Patients whose suicidal thoughts are ego-syntonic identify with the thoughts as representing themselves and take ownership of these thoughts. Such patients are at a greater risk of acting on suicidal thoughts.
Patients whose suicidal thoughts are ego-dystonic consider the suicidal thoughts foreign to their core self and do not believe such thoughts represent them. In essence, they “disown” the thoughts and typically want to control and eliminate them. Examples of patients’ ego-syntonic vs ego-dystonic suicidal thoughts are listed in Table 2.
This construct calls for an intervention to help patients who have ego-syntonic suicidal thoughts restructure them as a manifestation of BD, rather then the patient’s core self belief. The intervention emphasizes the patient is not “a suicidal patient” but suffers from an illness that may manifest with suicidal ideation. Many BD patients overly identify with their disease, stating, “I am bipolar” or “I am suicidal.” The “I am” statement originates from the verb “to be,” which implies the disease is part of the patient’s identity. The goal of this intervention is to help the patient learn to disidentify from the disease and decide that suicidal thoughts do not represent their core self, but are a manifestation of the underlying disease.
The psychosynthesis model of helping patients disidentify and therefore disown suicidal thoughts is compatible with interventions that use mindfulness-based cognitive therapy training to teach patients to experience their thoughts as just passing through their consciousness without taking ownership of them.17
Table 2
Examples of ego-syntonic vs ego-dystonic suicidal thoughts
| Ego-syntonic | Ego-dystonic |
|---|---|
| ‘I want to be dead. I found a simple and sure way to do it’ | ‘I am having suicidal thoughts again and I don’t like it’ |
| ‘I know my family will be better off without me’ | ‘I’m afraid the illness is coming back. I can’t stop these images’ |
| ‘Life is too hard, too much pain. I just want to end it all’ | ‘I see my body in a coffin. It scares the hell out of me’ |
| ‘I’ve come to the end, life for me is over and done’ | ‘I don’t want to die. Please help me get well again’ |
| ‘I know my life is over. I just have to find the right way to do it’ | ‘It is as if a part of me wants to die but the rest of me wants to live’ |
| ‘Nobody cares about me. It is as if I am already dead’ | ‘I know my family needs me. I want to be there for them’ |
| ‘I have nothing to live for’ | ‘I have so much to live for, why am I having such crazy thoughts?’ |
The intervention
Assessment of suicidality is a fundamental skill for every mental health clinician.18 The psychotherapeutic intervention I use integrates the cognitive therapy principles of reframing, relabeling, and restructuring patients’ thoughts with disidentification from dysfunctional thoughts, feelings, and desires, based on psychosynthesis principles.
First, I conduct a comprehensive mental status examination that includes an in-depth exploration of the patient’s suicidal thoughts to determine if they are ego-syntonic or ego-dystonic. I begin by asking patients to clarify and elaborate on their statements referring to suicide, asking questions such as “Is there a part of you that objects to these thoughts?” and “Is there a part of you that wants to live?” If a patient indicates that he or she does experience inner conflict regarding such thoughts, these thoughts are classified as ego-dystonic. If a patient does not have any counter thoughts regarding the suicidal thoughts and fully identifies with them, the thoughts are classified as ego-syntonic.
I follow this with a treatment plan that helps patients change their view of their suicidal thoughts. I ask the patient to change these suicidal thoughts to ego-dystonic by focusing on the following statement: “I, (patient’s name), am a human being and like all human beings, I have thoughts; however, I am not my thoughts, I am much more than that.” I ask my patient to read this out loud and to mindfully meditate on this statement several times a day to reinforce the new understanding that these suicidal thoughts are a manifestation of the chemical imbalance of the mood disorder, and do not represent the patient as a person.
This intervention is paired with a future-focused internalized imagery experience I have described in previous articles.19,20 In this part of the treatment, the patient and I discuss a specific expected life milestone that is positive and for which he or she would want to be present (eg, children graduating from high school or college, a wedding, birth of a child/grandchild, etc.). Using guided imagery, the patient experiences this event with all 5 senses during the session. I instruct the patient to internalize the experience and bring it back from the future to the present. This creates a “hook into the future” that is coupled with this desired milestone event in the patient’s life.
The following 3 case studies provide examples of the application of this treatment intervention.
CASE 1: Disidentifying family history
Mrs. G, a 42-year-old mother of 2, suffers from bipolar II disorder with recurrent episodes of depression associated with ego-syntonic suicidal thoughts. She states that at times she feels she is a burden to her husband and children and believes they may be better off without her. She says she believes “ending it all” must be her destiny. After further investigation, I learn Mrs. G has a family history of BD and 3 relatives have committed suicide. This family history may partially explain her belief that suicide must be “in her genes.”
I discuss with Mrs. G the strategy of changing her thoughts. I tell her to write in her journal—which she brings to her sessions—the following statements: “I am a human being. I am an adult woman and mother of 2 children. I know I have thoughts but I am not my thoughts, I am much more than that. I know I have genes but I am not my genes, I am much more than that. I know I have feelings, but I am not my feelings, I am much more than that. I know I have cousins, uncles, aunts, and other relatives but I am not my relatives. I am uniquely myself, different from the others.”
I ask Mrs. G to read these statements out loud and repeat them several times a day to reinforce this new way of perceiving the suicidal thoughts and to disidentify from the thoughts and her family history as it relates to suicide.
Mrs. G and I talk about the future and expected family milestones. When I ask if her son would want her to be present at his college graduation, she says yes. We then discuss in detail the date, time of day, and location of this event, followed by a guided imagery exercise focused on the graduation. She is guided to experience this event with all 5 senses and describes the event in detail, including the expression on the faces of her husband and children, their voices, and the scent of their aftershave lotion. She hears her son saying, “Mom, I love you. Thank you for being there with me all these years. I could not have done it without you.” I ask Mrs. G to internalize these experiences and carve them into her memory. She is instructed to come back from this future-focused guided imagery experience. When her eyes open, she looks at me and describes her experience in great detail, at times using the past tense, which confirms that the future-focused event was internalized.
In her next session, Mrs. G reports an improvement in her sleep and a change in her suicidal thoughts, which now are only fleeting.
CASE 2: Experiencing graduation
Ms. J, age 17, was diagnosed with bipolar I disorder when she was 15. She has a family history of BD in her mother, 2 maternal aunts, her grandmother, and an older sister. All these women have a history of suicidal thoughts and suicide attempts requiring hospital treatment, but no completed suicides.
Ms. J has been taking an adequate combination of mood stabilizers. She has recovered from 2 previous depressive episodes and is experiencing a third relapse with suicidal thoughts. At times, she experiences these thoughts as ego-syntonic; at other times, they are ego-dystonic.
I first educate her about the nature of BD, explaining that her suicidal thoughts are a manifestation of a chemical imbalance in her brain as a result of the depressive relapse. I teach her to use guided imagery to focus on her favorite place of peace and serenity, the beach, which produces immediate relief of the intense anxiety she felt.
After we complete the disidentification exercise, I ask her to focus on her high school graduation ceremony, which is scheduled to take place in 1 year. In a state of guided imagery, she experiences her graduation from high school with all 5 senses. As she returns to a state of full alertness with her eyes open, she describes the graduation ceremony experience in detail using the past tense, as if it had already occurred, thereby creating her own hook into the future. I instruct her to write about this experience in her journal and bring it with her to the next session.
The following session, Ms. J reports that her suicide ideations have “disappeared.” She says this was accompanied by improvements in her overall mood and sleep.
CASE 3: Internalizing the future
Mr. C, a 38-year-old married father of 4 children, has bipolar II disorder and is in a depressed state. He has been treated with optimal doses of mood stabilizers and atypical antipsychotics but continues to have suicidal thoughts. These thoughts are at times ego-syntonic; he says, “My family would be better off without me.” When Mr. C’s mood improves, however, the suicidal thoughts become more ego-dystonic; he expresses fear that he might act out on the thoughts and states that he does not want to die, he really wants to live and get better. He has no history of suicide attempts.
During our session, I ask Mr. C to focus on a new perspective to understand his thoughts by repeating the following statements: “I, JC, am a human being. I know I have a bipolar mood disorder; however, I must remember I am not bipolar. I have suicidal thoughts; however, I am not my thoughts, I am much more than that. I know I want to live, to heal, and to get better. I want to be alive and well so I can see and participate in my children’s graduation from high school and be there when they get married and when my grandchildren are born.”
I teach Mr. C to use guided imagery, during which he experiences such future positive images and milestones in his life in all 5 senses and internalizes them by using the “back from the future” technique.17 By the end of the session, he reports feeling better, more hopeful, and confident in his abilities to control his suicidal thoughts. I instruct him to write in his diary about his experiences with the future-focused positive milestones and to bring this assignment to his next appointment.
At his next appointment, Mr. C reports that his suicidal thoughts have become more fleeting, lasting for 10 to 30 seconds, and then spontaneously change to focus on issues of the “here and now.” When I ask him to read what he’s written, what stands out is the use of past tense verbs to describe future-focused experiences. For me, this confirms that Mr. C has internalized the future, creating the desirable “future hook” that acts as an antidote to the suicidal thoughts.
Related Resources
- Rouget BW, Aubry JM. Efficacy of psychoeducational approaches on bipolar disorders: a review of the literature. J Affect Disord. 2007;98:11-27.
- Weinberg I, Ronningstam E, Goldblatt MJ, et al. Strategies in treatment of suicidality: identification of common and treatment-specific interventions in empirically supported treatment manuals. J Clin Psychiatry. 2010;71:699-706.
Drug Brand Name
- Lithium • Eskalith, Lithobid
Disclosure
Dr. Torem reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. McIntyre RS, Konarski JZ. Bipolar disorder: a national health concern. CNS Spectr. 2004;9(11 suppl 12):6-15.
2. Tsai SY, Lee CH, Kuo CJ, et al. A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry. 2005;66(12):1586-1591.
3. Osby U, Brandt L, Correia N, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58(9):844-850.
4. Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: risks and management. CNS Spectr. 2006;11(6):465-471.
5. Gelenberg AJ. Can lithium help to prevent suicide? Acta Psychiatr Scand. 2001;104(3):161-162.
6. Schou M. Suicidal behavior and prophylactic lithium treatment of major mood disorders: a review of reviews. Suicide Life Threat Behav. 2001;30(3):289-293.
7. Burgess S, Geddes J, Hawton K, et al. Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev. 2001;(3):CD003013.-
8. Baldessarini RJ, Tondo L, Davis P, et al. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006;8(5 Pt 2):625-639.
9. Tondo L, Baldessarini RJ. Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients. Epidemiol Psichiatr Soc. 2009;18(3):179-183.
10. Miklowitz DJ. Adjunctive psychotherapy for bipolar disorder: state of the evidence. Am J Psychiatry. 2008;165(11):1408-1419.
11. Hirschfeld RMA, Harris TH, Davis HK. Making efficacious choices: the integration of pharmacotherapy and nonpharmacologic approaches to the treatment of patients with bipolar disorder. Current Psychiatry. 2009;8(10 suppl):S6-S11.
12. Rucci P, Frank E, Kostelnik B, et al. Suicide attempts in patients with bipolar I disorder during acute and maintenance phases of intensive treatment with pharmacotherapy and adjunctive psychotherapy. Am J Psychiatry. 2002;159(7):1160-1164.
13. Fountoulakis KN, Gonda X, Siamouli M, et al. Psychotherapeutic intervention and suicide risk reduction in bipolar disorder: a review of the evidence. J Affect Disord. 2009;113(1-2):21-29.
14. Pompili M, Rihmer Z, Innamorati M, et al. Assessment and treatment of suicide risk in bipolar disorders. Expert Rev Neurother. 2009;9(1):109-136.
15. Assagioli R. Psychosynthesis: a collection of basic writings. New York NY: The Viking Press Inc.; 1965.
16. Assagioli R. The act of will. New York NY: The Viking Press Inc.; 1973.
17. Williams JM, Alatiq Y, Crane C, et al. Mindfulness-based cognitive therapy (MBCT) in bipolar disorder: preliminary evaluation of immediate effects on between-episode functioning. J Affect Disord. 2008;107(1-3):275-279.
18. Shea SC. The delicate art of eliciting suicidal ideation. Psychiatric Annals. 2004;34:385-400.
19. Torem MS. “Back from the future”: a powerful age-progression technique. Am J Clin Hypn. 1992;35(2):81-88.
20. Torem MS. Treating depression: a remedy from the future. In: Yapko MD ed. Hypnosis and treating depression: applications in clinical practice. New York, NY: Routledge; 2006:97–119.
1. McIntyre RS, Konarski JZ. Bipolar disorder: a national health concern. CNS Spectr. 2004;9(11 suppl 12):6-15.
2. Tsai SY, Lee CH, Kuo CJ, et al. A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry. 2005;66(12):1586-1591.
3. Osby U, Brandt L, Correia N, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58(9):844-850.
4. Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: risks and management. CNS Spectr. 2006;11(6):465-471.
5. Gelenberg AJ. Can lithium help to prevent suicide? Acta Psychiatr Scand. 2001;104(3):161-162.
6. Schou M. Suicidal behavior and prophylactic lithium treatment of major mood disorders: a review of reviews. Suicide Life Threat Behav. 2001;30(3):289-293.
7. Burgess S, Geddes J, Hawton K, et al. Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev. 2001;(3):CD003013.-
8. Baldessarini RJ, Tondo L, Davis P, et al. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006;8(5 Pt 2):625-639.
9. Tondo L, Baldessarini RJ. Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients. Epidemiol Psichiatr Soc. 2009;18(3):179-183.
10. Miklowitz DJ. Adjunctive psychotherapy for bipolar disorder: state of the evidence. Am J Psychiatry. 2008;165(11):1408-1419.
11. Hirschfeld RMA, Harris TH, Davis HK. Making efficacious choices: the integration of pharmacotherapy and nonpharmacologic approaches to the treatment of patients with bipolar disorder. Current Psychiatry. 2009;8(10 suppl):S6-S11.
12. Rucci P, Frank E, Kostelnik B, et al. Suicide attempts in patients with bipolar I disorder during acute and maintenance phases of intensive treatment with pharmacotherapy and adjunctive psychotherapy. Am J Psychiatry. 2002;159(7):1160-1164.
13. Fountoulakis KN, Gonda X, Siamouli M, et al. Psychotherapeutic intervention and suicide risk reduction in bipolar disorder: a review of the evidence. J Affect Disord. 2009;113(1-2):21-29.
14. Pompili M, Rihmer Z, Innamorati M, et al. Assessment and treatment of suicide risk in bipolar disorders. Expert Rev Neurother. 2009;9(1):109-136.
15. Assagioli R. Psychosynthesis: a collection of basic writings. New York NY: The Viking Press Inc.; 1965.
16. Assagioli R. The act of will. New York NY: The Viking Press Inc.; 1973.
17. Williams JM, Alatiq Y, Crane C, et al. Mindfulness-based cognitive therapy (MBCT) in bipolar disorder: preliminary evaluation of immediate effects on between-episode functioning. J Affect Disord. 2008;107(1-3):275-279.
18. Shea SC. The delicate art of eliciting suicidal ideation. Psychiatric Annals. 2004;34:385-400.
19. Torem MS. “Back from the future”: a powerful age-progression technique. Am J Clin Hypn. 1992;35(2):81-88.
20. Torem MS. Treating depression: a remedy from the future. In: Yapko MD ed. Hypnosis and treating depression: applications in clinical practice. New York, NY: Routledge; 2006:97–119.
Off-Label Use of Atypical Antipsychotics Minimally Effective
Atypical antipsychotics are effective in only a few of the many off-label conditions for which they are currently used, according to a meta-analysis in the Sept. 28 issue of JAMA.
In particular, there is no good evidence to support the use of atypical antipsychotics for substance abuse disorder, eating disorders, or insomnia. And the evidence for using them for posttraumatic stress disorder and personality disorders is characterized as "mixed," said Dr. Alicia Ruelaz Maher of Rand Health, Southern California Evidence-Based Practice Center, Santa Monica, and her colleagues.
Atypical antipsychotics are approved for use in schizophrenia, bipolar disorder, and, for select agents, depression. But their use has rapidly increased in recent years, and it is estimated that their off-label use doubled between 1995 and 2008.
Dr. Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. For their meta-analysis, Dr. Maher and her colleagues included 162 efficacy trials and 231 trials or large observational studies that addressed adverse events (JAMA 2011;306:1359-69).
Among their findings were the following:
• "First, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment of behavioral symptoms in dementia." These drugs improved psychosis, agitation, and symptoms such as hallucinations, suspiciousness, dysphoria, anxiety, aggression, disinhibition, and apathy, though they did so only to a degree "considered to be the minimum clinically observable change."
• In three large and very recent trials not included in previous meta-analyses, quetiapine showed significant benefits for generalized anxiety disorder. However, "we classified the strength of evidence for this outcome as ‘moderate,’ based on the inconsistency of results and because all [the trials] were funded by manufacturers."
• Risperidone was associated with significant improvement in OCD. But that finding was tempered by the fact there may have been publication bias affecting the pooled results.
• "The strength of evidence has decreased from moderate to low for [use of] quetiapine in patients with OCD."
• New evidence indicates that atypical antipsychotics are ineffective for eating disorders and substance abuse disorder.
• The level of evidence is mixed regarding personality disorders, and is moderate for an association of risperidone with improving PTSD."
Dr. Maher and her colleagues cautioned that most of the studies they reviewed – for example, 27 of the 38 trials of dementia and 12 of the 14 trials of anxiety – were sponsored by drug manufacturers. And they found no studies at all on the off-label use of three newer atypical antipsychotic drugs: asenapine, iloperidone, and paliperidone.
In addition, studies published after June 1, 2011, including a large randomized, control trial of risperidone for patients with military-related PTSD and symptoms resistant to selective serotonin reuptake inhibitors, were not included in the current review.
Still, evidence found in the meta-analysis should provide guidance to clinicians who are considering off-label prescribing of atypical antipsychotics, the investigators wrote.
This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s colleagues reported ties to Eli Lilly.
Atypical antipsychotics are effective in only a few of the many off-label conditions for which they are currently used, according to a meta-analysis in the Sept. 28 issue of JAMA.
In particular, there is no good evidence to support the use of atypical antipsychotics for substance abuse disorder, eating disorders, or insomnia. And the evidence for using them for posttraumatic stress disorder and personality disorders is characterized as "mixed," said Dr. Alicia Ruelaz Maher of Rand Health, Southern California Evidence-Based Practice Center, Santa Monica, and her colleagues.
Atypical antipsychotics are approved for use in schizophrenia, bipolar disorder, and, for select agents, depression. But their use has rapidly increased in recent years, and it is estimated that their off-label use doubled between 1995 and 2008.
Dr. Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. For their meta-analysis, Dr. Maher and her colleagues included 162 efficacy trials and 231 trials or large observational studies that addressed adverse events (JAMA 2011;306:1359-69).
Among their findings were the following:
• "First, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment of behavioral symptoms in dementia." These drugs improved psychosis, agitation, and symptoms such as hallucinations, suspiciousness, dysphoria, anxiety, aggression, disinhibition, and apathy, though they did so only to a degree "considered to be the minimum clinically observable change."
• In three large and very recent trials not included in previous meta-analyses, quetiapine showed significant benefits for generalized anxiety disorder. However, "we classified the strength of evidence for this outcome as ‘moderate,’ based on the inconsistency of results and because all [the trials] were funded by manufacturers."
• Risperidone was associated with significant improvement in OCD. But that finding was tempered by the fact there may have been publication bias affecting the pooled results.
• "The strength of evidence has decreased from moderate to low for [use of] quetiapine in patients with OCD."
• New evidence indicates that atypical antipsychotics are ineffective for eating disorders and substance abuse disorder.
• The level of evidence is mixed regarding personality disorders, and is moderate for an association of risperidone with improving PTSD."
Dr. Maher and her colleagues cautioned that most of the studies they reviewed – for example, 27 of the 38 trials of dementia and 12 of the 14 trials of anxiety – were sponsored by drug manufacturers. And they found no studies at all on the off-label use of three newer atypical antipsychotic drugs: asenapine, iloperidone, and paliperidone.
In addition, studies published after June 1, 2011, including a large randomized, control trial of risperidone for patients with military-related PTSD and symptoms resistant to selective serotonin reuptake inhibitors, were not included in the current review.
Still, evidence found in the meta-analysis should provide guidance to clinicians who are considering off-label prescribing of atypical antipsychotics, the investigators wrote.
This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s colleagues reported ties to Eli Lilly.
Atypical antipsychotics are effective in only a few of the many off-label conditions for which they are currently used, according to a meta-analysis in the Sept. 28 issue of JAMA.
In particular, there is no good evidence to support the use of atypical antipsychotics for substance abuse disorder, eating disorders, or insomnia. And the evidence for using them for posttraumatic stress disorder and personality disorders is characterized as "mixed," said Dr. Alicia Ruelaz Maher of Rand Health, Southern California Evidence-Based Practice Center, Santa Monica, and her colleagues.
Atypical antipsychotics are approved for use in schizophrenia, bipolar disorder, and, for select agents, depression. But their use has rapidly increased in recent years, and it is estimated that their off-label use doubled between 1995 and 2008.
Dr. Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. For their meta-analysis, Dr. Maher and her colleagues included 162 efficacy trials and 231 trials or large observational studies that addressed adverse events (JAMA 2011;306:1359-69).
Among their findings were the following:
• "First, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment of behavioral symptoms in dementia." These drugs improved psychosis, agitation, and symptoms such as hallucinations, suspiciousness, dysphoria, anxiety, aggression, disinhibition, and apathy, though they did so only to a degree "considered to be the minimum clinically observable change."
• In three large and very recent trials not included in previous meta-analyses, quetiapine showed significant benefits for generalized anxiety disorder. However, "we classified the strength of evidence for this outcome as ‘moderate,’ based on the inconsistency of results and because all [the trials] were funded by manufacturers."
• Risperidone was associated with significant improvement in OCD. But that finding was tempered by the fact there may have been publication bias affecting the pooled results.
• "The strength of evidence has decreased from moderate to low for [use of] quetiapine in patients with OCD."
• New evidence indicates that atypical antipsychotics are ineffective for eating disorders and substance abuse disorder.
• The level of evidence is mixed regarding personality disorders, and is moderate for an association of risperidone with improving PTSD."
Dr. Maher and her colleagues cautioned that most of the studies they reviewed – for example, 27 of the 38 trials of dementia and 12 of the 14 trials of anxiety – were sponsored by drug manufacturers. And they found no studies at all on the off-label use of three newer atypical antipsychotic drugs: asenapine, iloperidone, and paliperidone.
In addition, studies published after June 1, 2011, including a large randomized, control trial of risperidone for patients with military-related PTSD and symptoms resistant to selective serotonin reuptake inhibitors, were not included in the current review.
Still, evidence found in the meta-analysis should provide guidance to clinicians who are considering off-label prescribing of atypical antipsychotics, the investigators wrote.
This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s colleagues reported ties to Eli Lilly.
FROM JAMA
Major Finding: Three atypical antipsychotic drugs are minimally effective for dementia, one is effective for generalized anxiety disorder, and one may be effective for OCD, but there is little evidence to support the off-label use of these agents in any other cases.
Data Source: A systematic review of 2,006 articles and a meta-analysis of 162 efficacy trials concerning the off-label use of atypical antipsychotic drugs.
Disclosures: This study was supported by the Agency for Healthcare Research and Quality, with some support from the Department of Veterans Affairs. One of Dr. Maher’s associates reported ties to Eli Lilly.
Opioid use disorder during pregnancy
For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.
Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.
After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.
Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.1 This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.2
Early identification is crucial
Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use3 and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.4 Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.5
Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.6
Chasnoff et al7 studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:
-
physical examination findings or history that suggests substance use or withdrawal symptoms
-
positive drug test results for illicit or nonprescribed opioids
-
aberrant medication-taking behaviors in those receiving prescribed opioids
-
nicotine or alcohol use in the month before they knew they were pregnant
-
a history of addiction-related disorders
-
evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
-
poor prenatal care attendance
-
unexplained fetal growth abnormalities.
Chasnoff et al demonstrated the reliability and effectiveness of a 1-minute, 5-item instrument (the “4 P’s Plus”) to screen for substance use, including heroin, during pregnancy (Table 1)8 In a study of 228 pregnant women, the overall internal consistency of this instrument was low but acceptable. More than three-quarters of patients (78%) were correctly classified as positive or negative, sensitivity was 87%, specificity was 76%, negative predictive validity was extremely high (97%), and positive predictive validity was low (36%). This low positive predictive validity may be acceptable in this population because over-identification of women at risk may be preferred to under-identification. The 4 P’s Plus identifies light and infrequent substance users who otherwise would go undetected, although it may place undue burden on providers to follow up on what later may be revealed to be a false positive screen.9 OUD-specific screening approaches are lacking; screening for general substance use is discussed elsewhere in the literature.10
A combination of interviewing and biologic drug screening may be more effective than either approach alone.11 Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.
Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.2
Stigma against pregnant women with OUD easily can erode therapeutic efforts. Perhaps the most important element of assessment is maximizing the therapeutic alliance to ensure that the patient complies with prenatal obstetric care and maternal addiction services. Pregnancy may be an opportune time to motivate women with OUD to make a change because they may be more open to receiving help.12 Motivational interventions are helpful for many but not all patients; the best approach to such interventions is still uncertain.13 Regardless of the mother’s motivation, prenatal care is fundamental.
Table 1 The ‘4P’s Plus’ screen for substance use during pregnancy
| Parents: Did either of your parents ever have a problem with alcohol or drugs? |
| Partner: Does your partner have a problem with alcohol or drugs? |
| Past: Have you ever drunk beer, wine, or liquor? |
| Pregnancy: In the month before you knew you were pregnant, how many cigarettes did you smoke? |
| In the month before you knew you were pregnant, how many beers/how much wine/ how much liquor did you drink? |
| A positive screen results when a patient answers either of the 2 questions relating to pregnancy, indicating any alcohol or tobacco use in the month before she knew she was pregnant |
| Source:Reference 8 |
Office management
OUD-specific treatment decreases opioid use and improves birth outcomes14; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.5 The Addiction Severity Index version tailored to women and pregnancy15 examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.16 Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.5,17,18
Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.5
Pregnant women with OUD should be screened for comorbid medical, obstetric, and psychiatric complications and referred accordingly (Table 2 and Table 3).6 Coordination among the patient’s psychiatrist, primary care provider, and obstetrician/gynecologist is essential. Programs that integrate these approaches into a single treatment team may be ideal. Although pregnancy per se may not be associated with higher risk of mental disorders, the risk of major depressive disorder may be increased during the postpartum period.19 Young, unmarried women with recent stressful life events, complicated pregnancies, and poor overall health may face a significantly increased risk of psychiatric illness during pregnancy.19 Patients whose opioid use has caused pregnancy complications may experience guilt and grief.
Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.12
Table 2 Medical complications common to pregnancy and substance abuse
| Anemia |
| Bacteremia/sepsis |
| Endocarditis |
| Cellulitis |
| Depression/anxiety |
| Gestational diabetes |
| Hepatitis (chronic and acute) |
| Hypertension/tachycardia |
| Phlebitis |
| Pneumonia |
| Gingivitis/poor oral hygiene |
| Sexually transmitted diseases |
|
|
| Tetanus |
| Cystitis |
| Pyelonephritis |
| AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus |
| Source:Reference 6 |
Table 3 Obstetric complications in women with addiction disorders
| Placental abruption |
| Chorioamnionitis |
| Placental insufficiency |
| Intrauterine growth restriction |
| Hypoxic/ischemic brain injury |
| Meconium passage |
| Neonatal abstinence syndrome |
| Spontaneous abortion |
| Intrauterine fetal death |
| Premature labor and delivery |
| Preterm, premature rupture of membranes |
| Postpartum hemorrhage |
| Hypertensive emergencies/preeclampsia |
| Source:Reference 6 |
Opioid agonist therapy
Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives (Table 4).20
Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:
-
their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
-
their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
-
research on the use of naltrexone during pregnancy is lacking.
Methadone has been used to treat OUD during pregnancy since the late 1970s.5 It requires adherence to strict federal regulations and is FDA pregnancy class C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate well-controlled studies in humans, but potential benefits may warrant use in pregnant women despite potential risks). Pregnant women have been safely maintained on methadone without adverse long-term maternal or fetal effects, and the National Institutes of Health recommends it as the standard of care for pregnant women with OUD. A woman steadily maintained on methadone is more likely to have a healthy pregnancy and infant than a woman who uses alcohol or other drugs.21 Further, the structure and services of methadone maintenance treatment can improve compliance with prenatal care and help prepare patients for parental responsibilities.
Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24
Buprenorphine is FDA pregnancy class C. Although not approved for use during pregnancy, it has been used successfully for pregnant patients with OUD.12,25 It is a partial agonist of the mu opioid receptor and an antagonist of the kappa opioid receptor, which may reduce its abuse liability and NAS severity.
The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.
Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.
In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29
Table 4 Opioid agonist treatment objectives for addicted patients who are pregnant
| General objectives |
| Prevent opioid withdrawal signs and symptoms |
| Provide a comfortable induction onto the medication |
| Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs |
| Enhance treatment retention |
| Create a more optimal environment for behavioral and psychosocial interventions |
| Pregnancy-specific objectives |
| Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs |
| Stabilize the intrauterine environment |
| Enhance involvement in prenatal care |
| Create an optimal environment to address pregnancy-specific problems |
| Source:Reference 20 |
Delivery and postnatal care
Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.30
During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.31 Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.
To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.
CASE CONTINUED: Medication change
Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.
After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.
Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.
Related Resources
-
Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
-
Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
-
Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
Drug Brand Names
Aripiprazole • Abilify
Buprenorphine and naloxone •Suboxone
Buprenorphine • Subutex
Butorphanol • Stadol
Citalopram • Celexa
Fentanyl • Duragesic, Sublimaze, others
Methadone • Dolophine
Naloxone • Narcan
Naltrexone • ReVia
Nalbuphine • Nubain
Oxycodone • Oxycontin
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.
For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.
Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.
After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.
Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.1 This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.2
Early identification is crucial
Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use3 and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.4 Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.5
Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.6
Chasnoff et al7 studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:
-
physical examination findings or history that suggests substance use or withdrawal symptoms
-
positive drug test results for illicit or nonprescribed opioids
-
aberrant medication-taking behaviors in those receiving prescribed opioids
-
nicotine or alcohol use in the month before they knew they were pregnant
-
a history of addiction-related disorders
-
evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
-
poor prenatal care attendance
-
unexplained fetal growth abnormalities.
Chasnoff et al demonstrated the reliability and effectiveness of a 1-minute, 5-item instrument (the “4 P’s Plus”) to screen for substance use, including heroin, during pregnancy (Table 1)8 In a study of 228 pregnant women, the overall internal consistency of this instrument was low but acceptable. More than three-quarters of patients (78%) were correctly classified as positive or negative, sensitivity was 87%, specificity was 76%, negative predictive validity was extremely high (97%), and positive predictive validity was low (36%). This low positive predictive validity may be acceptable in this population because over-identification of women at risk may be preferred to under-identification. The 4 P’s Plus identifies light and infrequent substance users who otherwise would go undetected, although it may place undue burden on providers to follow up on what later may be revealed to be a false positive screen.9 OUD-specific screening approaches are lacking; screening for general substance use is discussed elsewhere in the literature.10
A combination of interviewing and biologic drug screening may be more effective than either approach alone.11 Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.
Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.2
Stigma against pregnant women with OUD easily can erode therapeutic efforts. Perhaps the most important element of assessment is maximizing the therapeutic alliance to ensure that the patient complies with prenatal obstetric care and maternal addiction services. Pregnancy may be an opportune time to motivate women with OUD to make a change because they may be more open to receiving help.12 Motivational interventions are helpful for many but not all patients; the best approach to such interventions is still uncertain.13 Regardless of the mother’s motivation, prenatal care is fundamental.
Table 1 The ‘4P’s Plus’ screen for substance use during pregnancy
| Parents: Did either of your parents ever have a problem with alcohol or drugs? |
| Partner: Does your partner have a problem with alcohol or drugs? |
| Past: Have you ever drunk beer, wine, or liquor? |
| Pregnancy: In the month before you knew you were pregnant, how many cigarettes did you smoke? |
| In the month before you knew you were pregnant, how many beers/how much wine/ how much liquor did you drink? |
| A positive screen results when a patient answers either of the 2 questions relating to pregnancy, indicating any alcohol or tobacco use in the month before she knew she was pregnant |
| Source:Reference 8 |
Office management
OUD-specific treatment decreases opioid use and improves birth outcomes14; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.5 The Addiction Severity Index version tailored to women and pregnancy15 examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.16 Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.5,17,18
Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.5
Pregnant women with OUD should be screened for comorbid medical, obstetric, and psychiatric complications and referred accordingly (Table 2 and Table 3).6 Coordination among the patient’s psychiatrist, primary care provider, and obstetrician/gynecologist is essential. Programs that integrate these approaches into a single treatment team may be ideal. Although pregnancy per se may not be associated with higher risk of mental disorders, the risk of major depressive disorder may be increased during the postpartum period.19 Young, unmarried women with recent stressful life events, complicated pregnancies, and poor overall health may face a significantly increased risk of psychiatric illness during pregnancy.19 Patients whose opioid use has caused pregnancy complications may experience guilt and grief.
Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.12
Table 2 Medical complications common to pregnancy and substance abuse
| Anemia |
| Bacteremia/sepsis |
| Endocarditis |
| Cellulitis |
| Depression/anxiety |
| Gestational diabetes |
| Hepatitis (chronic and acute) |
| Hypertension/tachycardia |
| Phlebitis |
| Pneumonia |
| Gingivitis/poor oral hygiene |
| Sexually transmitted diseases |
|
|
| Tetanus |
| Cystitis |
| Pyelonephritis |
| AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus |
| Source:Reference 6 |
Table 3 Obstetric complications in women with addiction disorders
| Placental abruption |
| Chorioamnionitis |
| Placental insufficiency |
| Intrauterine growth restriction |
| Hypoxic/ischemic brain injury |
| Meconium passage |
| Neonatal abstinence syndrome |
| Spontaneous abortion |
| Intrauterine fetal death |
| Premature labor and delivery |
| Preterm, premature rupture of membranes |
| Postpartum hemorrhage |
| Hypertensive emergencies/preeclampsia |
| Source:Reference 6 |
Opioid agonist therapy
Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives (Table 4).20
Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:
-
their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
-
their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
-
research on the use of naltrexone during pregnancy is lacking.
Methadone has been used to treat OUD during pregnancy since the late 1970s.5 It requires adherence to strict federal regulations and is FDA pregnancy class C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate well-controlled studies in humans, but potential benefits may warrant use in pregnant women despite potential risks). Pregnant women have been safely maintained on methadone without adverse long-term maternal or fetal effects, and the National Institutes of Health recommends it as the standard of care for pregnant women with OUD. A woman steadily maintained on methadone is more likely to have a healthy pregnancy and infant than a woman who uses alcohol or other drugs.21 Further, the structure and services of methadone maintenance treatment can improve compliance with prenatal care and help prepare patients for parental responsibilities.
Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24
Buprenorphine is FDA pregnancy class C. Although not approved for use during pregnancy, it has been used successfully for pregnant patients with OUD.12,25 It is a partial agonist of the mu opioid receptor and an antagonist of the kappa opioid receptor, which may reduce its abuse liability and NAS severity.
The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.
Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.
In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29
Table 4 Opioid agonist treatment objectives for addicted patients who are pregnant
| General objectives |
| Prevent opioid withdrawal signs and symptoms |
| Provide a comfortable induction onto the medication |
| Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs |
| Enhance treatment retention |
| Create a more optimal environment for behavioral and psychosocial interventions |
| Pregnancy-specific objectives |
| Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs |
| Stabilize the intrauterine environment |
| Enhance involvement in prenatal care |
| Create an optimal environment to address pregnancy-specific problems |
| Source:Reference 20 |
Delivery and postnatal care
Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.30
During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.31 Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.
To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.
CASE CONTINUED: Medication change
Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.
After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.
Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.
Related Resources
-
Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
-
Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
-
Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
Drug Brand Names
Aripiprazole • Abilify
Buprenorphine and naloxone •Suboxone
Buprenorphine • Subutex
Butorphanol • Stadol
Citalopram • Celexa
Fentanyl • Duragesic, Sublimaze, others
Methadone • Dolophine
Naloxone • Narcan
Naltrexone • ReVia
Nalbuphine • Nubain
Oxycodone • Oxycontin
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.
For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.
Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.
After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.
Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.1 This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.2
Early identification is crucial
Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use3 and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.4 Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.5
Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.6
Chasnoff et al7 studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:
-
physical examination findings or history that suggests substance use or withdrawal symptoms
-
positive drug test results for illicit or nonprescribed opioids
-
aberrant medication-taking behaviors in those receiving prescribed opioids
-
nicotine or alcohol use in the month before they knew they were pregnant
-
a history of addiction-related disorders
-
evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
-
poor prenatal care attendance
-
unexplained fetal growth abnormalities.
Chasnoff et al demonstrated the reliability and effectiveness of a 1-minute, 5-item instrument (the “4 P’s Plus”) to screen for substance use, including heroin, during pregnancy (Table 1)8 In a study of 228 pregnant women, the overall internal consistency of this instrument was low but acceptable. More than three-quarters of patients (78%) were correctly classified as positive or negative, sensitivity was 87%, specificity was 76%, negative predictive validity was extremely high (97%), and positive predictive validity was low (36%). This low positive predictive validity may be acceptable in this population because over-identification of women at risk may be preferred to under-identification. The 4 P’s Plus identifies light and infrequent substance users who otherwise would go undetected, although it may place undue burden on providers to follow up on what later may be revealed to be a false positive screen.9 OUD-specific screening approaches are lacking; screening for general substance use is discussed elsewhere in the literature.10
A combination of interviewing and biologic drug screening may be more effective than either approach alone.11 Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.
Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.2
Stigma against pregnant women with OUD easily can erode therapeutic efforts. Perhaps the most important element of assessment is maximizing the therapeutic alliance to ensure that the patient complies with prenatal obstetric care and maternal addiction services. Pregnancy may be an opportune time to motivate women with OUD to make a change because they may be more open to receiving help.12 Motivational interventions are helpful for many but not all patients; the best approach to such interventions is still uncertain.13 Regardless of the mother’s motivation, prenatal care is fundamental.
Table 1 The ‘4P’s Plus’ screen for substance use during pregnancy
| Parents: Did either of your parents ever have a problem with alcohol or drugs? |
| Partner: Does your partner have a problem with alcohol or drugs? |
| Past: Have you ever drunk beer, wine, or liquor? |
| Pregnancy: In the month before you knew you were pregnant, how many cigarettes did you smoke? |
| In the month before you knew you were pregnant, how many beers/how much wine/ how much liquor did you drink? |
| A positive screen results when a patient answers either of the 2 questions relating to pregnancy, indicating any alcohol or tobacco use in the month before she knew she was pregnant |
| Source:Reference 8 |
Office management
OUD-specific treatment decreases opioid use and improves birth outcomes14; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.5 The Addiction Severity Index version tailored to women and pregnancy15 examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.16 Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.5,17,18
Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.5
Pregnant women with OUD should be screened for comorbid medical, obstetric, and psychiatric complications and referred accordingly (Table 2 and Table 3).6 Coordination among the patient’s psychiatrist, primary care provider, and obstetrician/gynecologist is essential. Programs that integrate these approaches into a single treatment team may be ideal. Although pregnancy per se may not be associated with higher risk of mental disorders, the risk of major depressive disorder may be increased during the postpartum period.19 Young, unmarried women with recent stressful life events, complicated pregnancies, and poor overall health may face a significantly increased risk of psychiatric illness during pregnancy.19 Patients whose opioid use has caused pregnancy complications may experience guilt and grief.
Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.12
Table 2 Medical complications common to pregnancy and substance abuse
| Anemia |
| Bacteremia/sepsis |
| Endocarditis |
| Cellulitis |
| Depression/anxiety |
| Gestational diabetes |
| Hepatitis (chronic and acute) |
| Hypertension/tachycardia |
| Phlebitis |
| Pneumonia |
| Gingivitis/poor oral hygiene |
| Sexually transmitted diseases |
|
|
| Tetanus |
| Cystitis |
| Pyelonephritis |
| AIDS: acquired immune deficiency syndrome; HIV: human immunodeficiency virus |
| Source:Reference 6 |
Table 3 Obstetric complications in women with addiction disorders
| Placental abruption |
| Chorioamnionitis |
| Placental insufficiency |
| Intrauterine growth restriction |
| Hypoxic/ischemic brain injury |
| Meconium passage |
| Neonatal abstinence syndrome |
| Spontaneous abortion |
| Intrauterine fetal death |
| Premature labor and delivery |
| Preterm, premature rupture of membranes |
| Postpartum hemorrhage |
| Hypertensive emergencies/preeclampsia |
| Source:Reference 6 |
Opioid agonist therapy
Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives (Table 4).20
Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:
-
their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
-
their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
-
research on the use of naltrexone during pregnancy is lacking.
Methadone has been used to treat OUD during pregnancy since the late 1970s.5 It requires adherence to strict federal regulations and is FDA pregnancy class C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate well-controlled studies in humans, but potential benefits may warrant use in pregnant women despite potential risks). Pregnant women have been safely maintained on methadone without adverse long-term maternal or fetal effects, and the National Institutes of Health recommends it as the standard of care for pregnant women with OUD. A woman steadily maintained on methadone is more likely to have a healthy pregnancy and infant than a woman who uses alcohol or other drugs.21 Further, the structure and services of methadone maintenance treatment can improve compliance with prenatal care and help prepare patients for parental responsibilities.
Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.22-24
Buprenorphine is FDA pregnancy class C. Although not approved for use during pregnancy, it has been used successfully for pregnant patients with OUD.12,25 It is a partial agonist of the mu opioid receptor and an antagonist of the kappa opioid receptor, which may reduce its abuse liability and NAS severity.
The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.28 However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.
Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.
In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.29
Table 4 Opioid agonist treatment objectives for addicted patients who are pregnant
| General objectives |
| Prevent opioid withdrawal signs and symptoms |
| Provide a comfortable induction onto the medication |
| Block the euphoric and reinforcing effects of illicit opioids while also attenuating the motivation (craving, social interactions) to use illicit opioids and other drugs |
| Enhance treatment retention |
| Create a more optimal environment for behavioral and psychosocial interventions |
| Pregnancy-specific objectives |
| Eliminate or reduce fetal exposure to illicit opioids and other illicit drugs |
| Stabilize the intrauterine environment |
| Enhance involvement in prenatal care |
| Create an optimal environment to address pregnancy-specific problems |
| Source:Reference 20 |
Delivery and postnatal care
Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.30
During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.31 Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.
To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.
CASE CONTINUED: Medication change
Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.
After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.
Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.
Related Resources
-
Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
-
Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
-
Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
Drug Brand Names
Aripiprazole • Abilify
Buprenorphine and naloxone •Suboxone
Buprenorphine • Subutex
Butorphanol • Stadol
Citalopram • Celexa
Fentanyl • Duragesic, Sublimaze, others
Methadone • Dolophine
Naloxone • Narcan
Naltrexone • ReVia
Nalbuphine • Nubain
Oxycodone • Oxycontin
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.
The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.
Does a Bipolar Disorder and Intelligence Link Matter?
The idea that bipolar disorder somehow links with creativity, intelligence, and even genius has an inescapable appeal and is a concept that has kicked around for at least a few decades. It seems somehow heartening to think that at least one psychiatric illness could have a bright side, that some people could productively harness a touch of mania to create notable works of art or literature. Psychologist and bipolar-disorder patient Kay Redfield Jamison published Touched With Fire in 1989, a book-length exploration of “manic depressive illness and the artistic temperament.”
The problem with looking anecdotally at the past lives of famous creators is that retrospective assessment of psychopathology introduces selection bias and lacks reliability. To get a better handle on the academic background of people who develop bipolar disorder, British psychiatrist Robin M. Murray and his associates ran a study, published last year, that reviewed Swedish national school records during 1988-1997 that included academic-performance assessments for more than 700,000 students at age 16 years. The researchers also examined Swedish hospital-discharge records for psychiatric hospitalizations through the end of 2003, which meant that each of the school kids had an average follow-up of more than 9 years for possible psychiatric hospitalization. During follow-up, 280 of the students had an initial hospitalization for bipolar disorder, and 483 had an initial hospitalization for schizophrenia.
As 16-year-old students, those with an academic assessment that exceeded average by more than two standard deviations had a statistically significant, threefold increased risk for later being diagnosed with bipolar disorder in an adjusted analysis that compared them with all the other students. Students on the low end academically, whose assessment at age 16 years put them more than two standard deviations below average, also had a significantly increased, twofold risk for later being diagnosed with bipolar disorder. In contrast, the risk for a later diagnosis of schizophrenia only increased among students at the low end academically. High academic performance at age 16 linked with protection against later developing schizophrenia.
An intriguing finding, but what does it mean? “Are bipolar genes associated with higher IQ or creativity?” Professor Murray asked after he reviewed this research in a talk earlier this month at the annual congress of the European College of Neuropsychopharmacology. He later told me his skepticism about the bipolar and creativity link, a skepticism that he believes other psychiatrists share. “I don’t think it’s accepted [among most psychiatrists], and I don’t think I accepted it,” he told me in an interview. “You do come across these families [where genius and psychiatric disease coexist]. It hasn’t been accepted, but it’s been there. What is more accepted is that patients with bipolar disorder tend to more often come from middle- and upper-class families than do patients with schizophrenia. You have to take it into account [when you speak with patients with bipolar disorder] that you’re talking with people who are smart, and it may help explain why the genes [predisposing people to develop bipolar disorder] have remained in the population,” Professor Murray ultimately characterized the notion of a creativity and bipolar link as “folklore.”
Whether true or not, the problem with viewing bipolar disorder as possibly having the positive side of conferring on at least some patients a “creative,” muse-like impulse is that I believe it diminishes the real risks that bipolar disorder poses to affected patients and to their friends and family. I spoke recently to a person who had been married to a bipolar patient and heard about the scary, horrific episodes of destructive and self-destructive behavior the illness triggered. The debilitating reality of uncontrolled bipolar disorder makes the hypothesis of a link between bipolar and creativity seem inconsequential.
---Mitchel Zoler (on Twitter @mitchelzoler)
The idea that bipolar disorder somehow links with creativity, intelligence, and even genius has an inescapable appeal and is a concept that has kicked around for at least a few decades. It seems somehow heartening to think that at least one psychiatric illness could have a bright side, that some people could productively harness a touch of mania to create notable works of art or literature. Psychologist and bipolar-disorder patient Kay Redfield Jamison published Touched With Fire in 1989, a book-length exploration of “manic depressive illness and the artistic temperament.”
The problem with looking anecdotally at the past lives of famous creators is that retrospective assessment of psychopathology introduces selection bias and lacks reliability. To get a better handle on the academic background of people who develop bipolar disorder, British psychiatrist Robin M. Murray and his associates ran a study, published last year, that reviewed Swedish national school records during 1988-1997 that included academic-performance assessments for more than 700,000 students at age 16 years. The researchers also examined Swedish hospital-discharge records for psychiatric hospitalizations through the end of 2003, which meant that each of the school kids had an average follow-up of more than 9 years for possible psychiatric hospitalization. During follow-up, 280 of the students had an initial hospitalization for bipolar disorder, and 483 had an initial hospitalization for schizophrenia.
As 16-year-old students, those with an academic assessment that exceeded average by more than two standard deviations had a statistically significant, threefold increased risk for later being diagnosed with bipolar disorder in an adjusted analysis that compared them with all the other students. Students on the low end academically, whose assessment at age 16 years put them more than two standard deviations below average, also had a significantly increased, twofold risk for later being diagnosed with bipolar disorder. In contrast, the risk for a later diagnosis of schizophrenia only increased among students at the low end academically. High academic performance at age 16 linked with protection against later developing schizophrenia.
An intriguing finding, but what does it mean? “Are bipolar genes associated with higher IQ or creativity?” Professor Murray asked after he reviewed this research in a talk earlier this month at the annual congress of the European College of Neuropsychopharmacology. He later told me his skepticism about the bipolar and creativity link, a skepticism that he believes other psychiatrists share. “I don’t think it’s accepted [among most psychiatrists], and I don’t think I accepted it,” he told me in an interview. “You do come across these families [where genius and psychiatric disease coexist]. It hasn’t been accepted, but it’s been there. What is more accepted is that patients with bipolar disorder tend to more often come from middle- and upper-class families than do patients with schizophrenia. You have to take it into account [when you speak with patients with bipolar disorder] that you’re talking with people who are smart, and it may help explain why the genes [predisposing people to develop bipolar disorder] have remained in the population,” Professor Murray ultimately characterized the notion of a creativity and bipolar link as “folklore.”
Whether true or not, the problem with viewing bipolar disorder as possibly having the positive side of conferring on at least some patients a “creative,” muse-like impulse is that I believe it diminishes the real risks that bipolar disorder poses to affected patients and to their friends and family. I spoke recently to a person who had been married to a bipolar patient and heard about the scary, horrific episodes of destructive and self-destructive behavior the illness triggered. The debilitating reality of uncontrolled bipolar disorder makes the hypothesis of a link between bipolar and creativity seem inconsequential.
---Mitchel Zoler (on Twitter @mitchelzoler)
The idea that bipolar disorder somehow links with creativity, intelligence, and even genius has an inescapable appeal and is a concept that has kicked around for at least a few decades. It seems somehow heartening to think that at least one psychiatric illness could have a bright side, that some people could productively harness a touch of mania to create notable works of art or literature. Psychologist and bipolar-disorder patient Kay Redfield Jamison published Touched With Fire in 1989, a book-length exploration of “manic depressive illness and the artistic temperament.”
The problem with looking anecdotally at the past lives of famous creators is that retrospective assessment of psychopathology introduces selection bias and lacks reliability. To get a better handle on the academic background of people who develop bipolar disorder, British psychiatrist Robin M. Murray and his associates ran a study, published last year, that reviewed Swedish national school records during 1988-1997 that included academic-performance assessments for more than 700,000 students at age 16 years. The researchers also examined Swedish hospital-discharge records for psychiatric hospitalizations through the end of 2003, which meant that each of the school kids had an average follow-up of more than 9 years for possible psychiatric hospitalization. During follow-up, 280 of the students had an initial hospitalization for bipolar disorder, and 483 had an initial hospitalization for schizophrenia.
As 16-year-old students, those with an academic assessment that exceeded average by more than two standard deviations had a statistically significant, threefold increased risk for later being diagnosed with bipolar disorder in an adjusted analysis that compared them with all the other students. Students on the low end academically, whose assessment at age 16 years put them more than two standard deviations below average, also had a significantly increased, twofold risk for later being diagnosed with bipolar disorder. In contrast, the risk for a later diagnosis of schizophrenia only increased among students at the low end academically. High academic performance at age 16 linked with protection against later developing schizophrenia.
An intriguing finding, but what does it mean? “Are bipolar genes associated with higher IQ or creativity?” Professor Murray asked after he reviewed this research in a talk earlier this month at the annual congress of the European College of Neuropsychopharmacology. He later told me his skepticism about the bipolar and creativity link, a skepticism that he believes other psychiatrists share. “I don’t think it’s accepted [among most psychiatrists], and I don’t think I accepted it,” he told me in an interview. “You do come across these families [where genius and psychiatric disease coexist]. It hasn’t been accepted, but it’s been there. What is more accepted is that patients with bipolar disorder tend to more often come from middle- and upper-class families than do patients with schizophrenia. You have to take it into account [when you speak with patients with bipolar disorder] that you’re talking with people who are smart, and it may help explain why the genes [predisposing people to develop bipolar disorder] have remained in the population,” Professor Murray ultimately characterized the notion of a creativity and bipolar link as “folklore.”
Whether true or not, the problem with viewing bipolar disorder as possibly having the positive side of conferring on at least some patients a “creative,” muse-like impulse is that I believe it diminishes the real risks that bipolar disorder poses to affected patients and to their friends and family. I spoke recently to a person who had been married to a bipolar patient and heard about the scary, horrific episodes of destructive and self-destructive behavior the illness triggered. The debilitating reality of uncontrolled bipolar disorder makes the hypothesis of a link between bipolar and creativity seem inconsequential.
---Mitchel Zoler (on Twitter @mitchelzoler)