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COVID-19 prompts ‘lifesaving’ policy change for opioid addiction
In the face of the US COVID-19 pandemic, the US Substance Abuse and Mental Health Services Administration (SAMHSA) has announced policy changes to allow some patients in opioid treatment programs (OTP) to take home their medication.
According to the agency, states may request “blanket exceptions” for all stable patients in an OTP to receive a 28-day supply of take-home doses of medications such as methadone and buprenorphine, which are used to treat opioid use disorder (OUD).
States may request up to 14 days of take-home medication for patients who are less stable but who can, in the judgment of OTP clinicians, safely handle this level of take-home medication.
“SAMHSA recognizes the evolving issues surrounding COVID-19 and the emerging needs OTPs continue to face,” the agency writes in its updated guidance.
“SAMHSA affirms its commitment to supporting OTPs in any way possible during this time. As such, we are expanding our previous guidance to provide increased flexibility,” the agency said.
A ‘Lifesaving’ Decision
Commenting on the SAMHSA policy change, Richard Saitz, MD, professor and chair of the department of community health sciences, Boston University School of Public Health, said, the policy “is not only a good idea, it is critical and lifesaving.”
“This approach had to be done now. With the reduction in face-to-face visits, patients with opioid use disorder need a way to access treatment. If they cannot get opioid agonists, they would withdraw and return to illicit opioid use and high overdose risk and it would be cruel,” said Saitz.
“It is possible that there will be some diversion and some risk of overdose or misuse, but even for less stable patients the benefit likely far outweighs the risk,” he told Medscape Medical News.
Saitz believes policy changes like this should have been made before a crisis.
“Honestly, this is perhaps a silver lining of the crisis” and could lead to permanent change in how OUD is treated in the US, he said.
“Just like we are learning what can be done without a medical in-person visit, we will learn that it is perfectly fine to treat patients with addiction more like we treat patients with other chronic diseases who take medication that has risks and benefits,” Saitz said.
in cases when a patient is quarantined because of coronavirus.
Typically, only licensed practitioners can dispense or administer OUD medications to patients, but during the COVID-19 crisis, treatment program staff members, law enforcement officers, and national guard personnel will be allowed to deliver OUD medications to an approved “lockbox” at the patient’s doorstep. The change applies only while the coronavirus public health emergency lasts.
“This is also an excellent idea,” Saitz said.
ASAM Also Responds
In addition, the American Society of Addiction Medicine (ASAM) released a focused update to its National Practice Guideline for the Treatment of Opioid Use Disorder (NPG).
The update is “especially critical in the context of the ongoing COVID-19 emergency, which threatens to curtail patient access to evidence-based treatment,” the organization said in a news release. The new document updates the 2015 NPG. It includes 13 new recommendations and major revisions to 35 existing recommendations.
One new recommendation states that comprehensive assessment of a patient is critical for treatment planning, but completing all assessments should not delay or preclude initiating pharmacotherapy for OUD. Another new recommendation states that there is no recommended time limit for pharmacotherapy.
ASAM continues to recommend that patients’ psychosocial needs be assessed and psychosocial treatment offered. However, if patients can’t access psychosocial treatment because they are in isolation or have other risk factors that preclude external interactions, clinicians should not delay initiation of medication for the treatment of addiction.
Expanding the use of telemedicine might also be appropriate for many patients, ASAM announced.
They note that the NPG is the first to address in a single document all medications currently approved by the US Food and Drug Administration to treat OUD and opioid withdrawal, including all available buprenorphine formulations.
“All of the updated recommendations are designed to both improve the quality and consistency of care and reduce barriers to access to care for Americans living with OUD. The updated recommendations aim to support initiation of buprenorphine treatment in the emergency department and other urgent care settings,” the society said in the release.
“In addition, [the recommendations] provide greater flexibility on dosing during the initiation of buprenorphine treatment and for initiation of buprenorphine at home (which is also an important change in the midst of the COVID-19 crisis).”
The full document is available online.
This article first appeared on Medscape.com.
In the face of the US COVID-19 pandemic, the US Substance Abuse and Mental Health Services Administration (SAMHSA) has announced policy changes to allow some patients in opioid treatment programs (OTP) to take home their medication.
According to the agency, states may request “blanket exceptions” for all stable patients in an OTP to receive a 28-day supply of take-home doses of medications such as methadone and buprenorphine, which are used to treat opioid use disorder (OUD).
States may request up to 14 days of take-home medication for patients who are less stable but who can, in the judgment of OTP clinicians, safely handle this level of take-home medication.
“SAMHSA recognizes the evolving issues surrounding COVID-19 and the emerging needs OTPs continue to face,” the agency writes in its updated guidance.
“SAMHSA affirms its commitment to supporting OTPs in any way possible during this time. As such, we are expanding our previous guidance to provide increased flexibility,” the agency said.
A ‘Lifesaving’ Decision
Commenting on the SAMHSA policy change, Richard Saitz, MD, professor and chair of the department of community health sciences, Boston University School of Public Health, said, the policy “is not only a good idea, it is critical and lifesaving.”
“This approach had to be done now. With the reduction in face-to-face visits, patients with opioid use disorder need a way to access treatment. If they cannot get opioid agonists, they would withdraw and return to illicit opioid use and high overdose risk and it would be cruel,” said Saitz.
“It is possible that there will be some diversion and some risk of overdose or misuse, but even for less stable patients the benefit likely far outweighs the risk,” he told Medscape Medical News.
Saitz believes policy changes like this should have been made before a crisis.
“Honestly, this is perhaps a silver lining of the crisis” and could lead to permanent change in how OUD is treated in the US, he said.
“Just like we are learning what can be done without a medical in-person visit, we will learn that it is perfectly fine to treat patients with addiction more like we treat patients with other chronic diseases who take medication that has risks and benefits,” Saitz said.
in cases when a patient is quarantined because of coronavirus.
Typically, only licensed practitioners can dispense or administer OUD medications to patients, but during the COVID-19 crisis, treatment program staff members, law enforcement officers, and national guard personnel will be allowed to deliver OUD medications to an approved “lockbox” at the patient’s doorstep. The change applies only while the coronavirus public health emergency lasts.
“This is also an excellent idea,” Saitz said.
ASAM Also Responds
In addition, the American Society of Addiction Medicine (ASAM) released a focused update to its National Practice Guideline for the Treatment of Opioid Use Disorder (NPG).
The update is “especially critical in the context of the ongoing COVID-19 emergency, which threatens to curtail patient access to evidence-based treatment,” the organization said in a news release. The new document updates the 2015 NPG. It includes 13 new recommendations and major revisions to 35 existing recommendations.
One new recommendation states that comprehensive assessment of a patient is critical for treatment planning, but completing all assessments should not delay or preclude initiating pharmacotherapy for OUD. Another new recommendation states that there is no recommended time limit for pharmacotherapy.
ASAM continues to recommend that patients’ psychosocial needs be assessed and psychosocial treatment offered. However, if patients can’t access psychosocial treatment because they are in isolation or have other risk factors that preclude external interactions, clinicians should not delay initiation of medication for the treatment of addiction.
Expanding the use of telemedicine might also be appropriate for many patients, ASAM announced.
They note that the NPG is the first to address in a single document all medications currently approved by the US Food and Drug Administration to treat OUD and opioid withdrawal, including all available buprenorphine formulations.
“All of the updated recommendations are designed to both improve the quality and consistency of care and reduce barriers to access to care for Americans living with OUD. The updated recommendations aim to support initiation of buprenorphine treatment in the emergency department and other urgent care settings,” the society said in the release.
“In addition, [the recommendations] provide greater flexibility on dosing during the initiation of buprenorphine treatment and for initiation of buprenorphine at home (which is also an important change in the midst of the COVID-19 crisis).”
The full document is available online.
This article first appeared on Medscape.com.
In the face of the US COVID-19 pandemic, the US Substance Abuse and Mental Health Services Administration (SAMHSA) has announced policy changes to allow some patients in opioid treatment programs (OTP) to take home their medication.
According to the agency, states may request “blanket exceptions” for all stable patients in an OTP to receive a 28-day supply of take-home doses of medications such as methadone and buprenorphine, which are used to treat opioid use disorder (OUD).
States may request up to 14 days of take-home medication for patients who are less stable but who can, in the judgment of OTP clinicians, safely handle this level of take-home medication.
“SAMHSA recognizes the evolving issues surrounding COVID-19 and the emerging needs OTPs continue to face,” the agency writes in its updated guidance.
“SAMHSA affirms its commitment to supporting OTPs in any way possible during this time. As such, we are expanding our previous guidance to provide increased flexibility,” the agency said.
A ‘Lifesaving’ Decision
Commenting on the SAMHSA policy change, Richard Saitz, MD, professor and chair of the department of community health sciences, Boston University School of Public Health, said, the policy “is not only a good idea, it is critical and lifesaving.”
“This approach had to be done now. With the reduction in face-to-face visits, patients with opioid use disorder need a way to access treatment. If they cannot get opioid agonists, they would withdraw and return to illicit opioid use and high overdose risk and it would be cruel,” said Saitz.
“It is possible that there will be some diversion and some risk of overdose or misuse, but even for less stable patients the benefit likely far outweighs the risk,” he told Medscape Medical News.
Saitz believes policy changes like this should have been made before a crisis.
“Honestly, this is perhaps a silver lining of the crisis” and could lead to permanent change in how OUD is treated in the US, he said.
“Just like we are learning what can be done without a medical in-person visit, we will learn that it is perfectly fine to treat patients with addiction more like we treat patients with other chronic diseases who take medication that has risks and benefits,” Saitz said.
in cases when a patient is quarantined because of coronavirus.
Typically, only licensed practitioners can dispense or administer OUD medications to patients, but during the COVID-19 crisis, treatment program staff members, law enforcement officers, and national guard personnel will be allowed to deliver OUD medications to an approved “lockbox” at the patient’s doorstep. The change applies only while the coronavirus public health emergency lasts.
“This is also an excellent idea,” Saitz said.
ASAM Also Responds
In addition, the American Society of Addiction Medicine (ASAM) released a focused update to its National Practice Guideline for the Treatment of Opioid Use Disorder (NPG).
The update is “especially critical in the context of the ongoing COVID-19 emergency, which threatens to curtail patient access to evidence-based treatment,” the organization said in a news release. The new document updates the 2015 NPG. It includes 13 new recommendations and major revisions to 35 existing recommendations.
One new recommendation states that comprehensive assessment of a patient is critical for treatment planning, but completing all assessments should not delay or preclude initiating pharmacotherapy for OUD. Another new recommendation states that there is no recommended time limit for pharmacotherapy.
ASAM continues to recommend that patients’ psychosocial needs be assessed and psychosocial treatment offered. However, if patients can’t access psychosocial treatment because they are in isolation or have other risk factors that preclude external interactions, clinicians should not delay initiation of medication for the treatment of addiction.
Expanding the use of telemedicine might also be appropriate for many patients, ASAM announced.
They note that the NPG is the first to address in a single document all medications currently approved by the US Food and Drug Administration to treat OUD and opioid withdrawal, including all available buprenorphine formulations.
“All of the updated recommendations are designed to both improve the quality and consistency of care and reduce barriers to access to care for Americans living with OUD. The updated recommendations aim to support initiation of buprenorphine treatment in the emergency department and other urgent care settings,” the society said in the release.
“In addition, [the recommendations] provide greater flexibility on dosing during the initiation of buprenorphine treatment and for initiation of buprenorphine at home (which is also an important change in the midst of the COVID-19 crisis).”
The full document is available online.
This article first appeared on Medscape.com.
ERAS protocol for cesarean delivery reduces opioid usage
GRAPEVINE, TEX. – An enhanced recovery after surgery (ERAS) pathway for cesarean delivery decreased postoperative opioid usage by 62% in one health care organization, researchers reported at the Pregnancy Meeting. The protocol incorporates a stepwise approach to pain control with no scheduled postoperative opioids.
Abington Jefferson Health, which includes two hospitals in Pennsylvania, implemented an ERAS pathway for all cesarean deliveries in October 2018. Kathryn Ruymann, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Ruymann is an obstetrics and gynecology resident at Abington Jefferson Health.
Prior to the ERAS protocol, 99%-100% of patients took an opioid during the postoperative period. “With ERAS, 26% of patients never took an opioid during the postop period,” Dr. Ruymann and her associates reported. “Pain scores decreased with ERAS for postoperative days 1-3 and remained unchanged on day 4.”
One in 300 opioid-naive patients who receives opioids after cesarean delivery becomes a persistent user, one study has shown (Am J Obstet Gynecol. 2016 Sep; 215(3):353.e1-18). “ERAS pathways integrate evidence-based interventions before, during, and after surgery to optimize outcomes, specifically to decrease postoperative opioid use,” the researchers said.
While other surgical fields have adopted ERAS pathways, more research is needed in obstetrics, said Dr. Ruymann. More than 4,500 women deliver at Abington Jefferson Health each year, and about a third undergo cesarean deliveries.
The organization’s ERAS pathway incorporates preoperative education, fasting guidelines, and intraoperative analgesia, nausea prophylaxis, and antimicrobial therapy. Under the new protocol, postoperative analgesia includes scheduled administration of nonopioid medications, including celecoxib and acetaminophen. In addition, patients may take 5-10 mg of oxycodone orally every 4 hours as needed, and hydromorphone 0.4 mg IV as needed may be used for refractory pain. In addition, patients should resume eating as soon as tolerated and be out of bed within 4 hours after surgery, according to the protocol. Postoperative management of pruritus and instructions on how to wean off opioids at home are among the other elements of the enhanced recovery plan.
To examine postoperative opioid usage before and after implementation of the ERAS pathway, the investigators conducted a retrospective cohort study of 316 women who underwent cesarean delivery 3 months before the start of the ERAS pathway and 267 who underwent cesarean delivery 3 months after. The researchers used an application developed in Qlik Sense, a data analytics platform, to calculate opioid usage.
Mean postoperative opioid use decreased by 62%. The reduction in opioid use remained 8 months after starting the ERAS pathway.
“An ERAS pathway for [cesarean delivery] decreases postoperative opioid usage by integrating a multimodal stepwise approach to pain control and recovery,” the researchers said. “Standardized order sets and departmentwide education were crucial in the success of ERAS. Additional research is needed to evaluate the impact of unique components of ERAS in order to optimize this pathway.”
The researchers had no disclosures.
SOURCE: Ruymann K et al. Am J Obstet Gynecol. 2020 Jan;222(1):S212, Abstract 315.
GRAPEVINE, TEX. – An enhanced recovery after surgery (ERAS) pathway for cesarean delivery decreased postoperative opioid usage by 62% in one health care organization, researchers reported at the Pregnancy Meeting. The protocol incorporates a stepwise approach to pain control with no scheduled postoperative opioids.
Abington Jefferson Health, which includes two hospitals in Pennsylvania, implemented an ERAS pathway for all cesarean deliveries in October 2018. Kathryn Ruymann, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Ruymann is an obstetrics and gynecology resident at Abington Jefferson Health.
Prior to the ERAS protocol, 99%-100% of patients took an opioid during the postoperative period. “With ERAS, 26% of patients never took an opioid during the postop period,” Dr. Ruymann and her associates reported. “Pain scores decreased with ERAS for postoperative days 1-3 and remained unchanged on day 4.”
One in 300 opioid-naive patients who receives opioids after cesarean delivery becomes a persistent user, one study has shown (Am J Obstet Gynecol. 2016 Sep; 215(3):353.e1-18). “ERAS pathways integrate evidence-based interventions before, during, and after surgery to optimize outcomes, specifically to decrease postoperative opioid use,” the researchers said.
While other surgical fields have adopted ERAS pathways, more research is needed in obstetrics, said Dr. Ruymann. More than 4,500 women deliver at Abington Jefferson Health each year, and about a third undergo cesarean deliveries.
The organization’s ERAS pathway incorporates preoperative education, fasting guidelines, and intraoperative analgesia, nausea prophylaxis, and antimicrobial therapy. Under the new protocol, postoperative analgesia includes scheduled administration of nonopioid medications, including celecoxib and acetaminophen. In addition, patients may take 5-10 mg of oxycodone orally every 4 hours as needed, and hydromorphone 0.4 mg IV as needed may be used for refractory pain. In addition, patients should resume eating as soon as tolerated and be out of bed within 4 hours after surgery, according to the protocol. Postoperative management of pruritus and instructions on how to wean off opioids at home are among the other elements of the enhanced recovery plan.
To examine postoperative opioid usage before and after implementation of the ERAS pathway, the investigators conducted a retrospective cohort study of 316 women who underwent cesarean delivery 3 months before the start of the ERAS pathway and 267 who underwent cesarean delivery 3 months after. The researchers used an application developed in Qlik Sense, a data analytics platform, to calculate opioid usage.
Mean postoperative opioid use decreased by 62%. The reduction in opioid use remained 8 months after starting the ERAS pathway.
“An ERAS pathway for [cesarean delivery] decreases postoperative opioid usage by integrating a multimodal stepwise approach to pain control and recovery,” the researchers said. “Standardized order sets and departmentwide education were crucial in the success of ERAS. Additional research is needed to evaluate the impact of unique components of ERAS in order to optimize this pathway.”
The researchers had no disclosures.
SOURCE: Ruymann K et al. Am J Obstet Gynecol. 2020 Jan;222(1):S212, Abstract 315.
GRAPEVINE, TEX. – An enhanced recovery after surgery (ERAS) pathway for cesarean delivery decreased postoperative opioid usage by 62% in one health care organization, researchers reported at the Pregnancy Meeting. The protocol incorporates a stepwise approach to pain control with no scheduled postoperative opioids.
Abington Jefferson Health, which includes two hospitals in Pennsylvania, implemented an ERAS pathway for all cesarean deliveries in October 2018. Kathryn Ruymann, MD, said at the meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Ruymann is an obstetrics and gynecology resident at Abington Jefferson Health.
Prior to the ERAS protocol, 99%-100% of patients took an opioid during the postoperative period. “With ERAS, 26% of patients never took an opioid during the postop period,” Dr. Ruymann and her associates reported. “Pain scores decreased with ERAS for postoperative days 1-3 and remained unchanged on day 4.”
One in 300 opioid-naive patients who receives opioids after cesarean delivery becomes a persistent user, one study has shown (Am J Obstet Gynecol. 2016 Sep; 215(3):353.e1-18). “ERAS pathways integrate evidence-based interventions before, during, and after surgery to optimize outcomes, specifically to decrease postoperative opioid use,” the researchers said.
While other surgical fields have adopted ERAS pathways, more research is needed in obstetrics, said Dr. Ruymann. More than 4,500 women deliver at Abington Jefferson Health each year, and about a third undergo cesarean deliveries.
The organization’s ERAS pathway incorporates preoperative education, fasting guidelines, and intraoperative analgesia, nausea prophylaxis, and antimicrobial therapy. Under the new protocol, postoperative analgesia includes scheduled administration of nonopioid medications, including celecoxib and acetaminophen. In addition, patients may take 5-10 mg of oxycodone orally every 4 hours as needed, and hydromorphone 0.4 mg IV as needed may be used for refractory pain. In addition, patients should resume eating as soon as tolerated and be out of bed within 4 hours after surgery, according to the protocol. Postoperative management of pruritus and instructions on how to wean off opioids at home are among the other elements of the enhanced recovery plan.
To examine postoperative opioid usage before and after implementation of the ERAS pathway, the investigators conducted a retrospective cohort study of 316 women who underwent cesarean delivery 3 months before the start of the ERAS pathway and 267 who underwent cesarean delivery 3 months after. The researchers used an application developed in Qlik Sense, a data analytics platform, to calculate opioid usage.
Mean postoperative opioid use decreased by 62%. The reduction in opioid use remained 8 months after starting the ERAS pathway.
“An ERAS pathway for [cesarean delivery] decreases postoperative opioid usage by integrating a multimodal stepwise approach to pain control and recovery,” the researchers said. “Standardized order sets and departmentwide education were crucial in the success of ERAS. Additional research is needed to evaluate the impact of unique components of ERAS in order to optimize this pathway.”
The researchers had no disclosures.
SOURCE: Ruymann K et al. Am J Obstet Gynecol. 2020 Jan;222(1):S212, Abstract 315.
REPORTING FROM THE PREGNANCY MEETING
Kratom: What we know, what to tell your patients
Mitragyna speciosa, better known as kratom, is a tropical evergreen tree that is native to Southeast Asia. Botanically, it is a member of the Rubiaceae family, as is the coffee plant, and physical laborers among indigenous populations have historically chewed the leaves or brewed them as a tea to improve endurance and reduce fatigue.1 Kratom is psychoactive; small amounts (up to 5 g of plant material) possess stimulant properties, while larger doses (>5 g) produce opioid-like, sedative, euphoric, and antinociceptive effects.2
In recent years, kratom has gained popularity in Western parts of the world due to its unique properties and perceived safety as a botanical product. Individuals may use kratom to boost their energy, relieve pain, or treat a wide range of physical or mood problems. Increasingly, kratom is being used by people who abuse opioids to self-manage opioid withdrawal, or for its euphoric effects. But kratom carries several important risks, including addiction, serious adverse effects, and possibly death. In this article, we review the epidemiology and pharmacology of kratom, and provide some guidance for educating patients about this substance.
Widely used but not FDA approved
Although kratom is not regulated or approved by the FDA, 3 to 5 million Americans use it regularly.3 According to an internet survey, kratom users are mostly college-educated, employed white men, age 31 to 50, who take the substance to manage pain or to treat general anxiety and mood disorders.4 Some individuals use kratom as an opioid substitute to reduce symptoms of opioid withdrawal.4
Kratom is available from a wide range of manufacturers in various formulations, including powders, tablets, liquids, and gum. It is sometimes sold in combination with other agents as a single product. Low-cost, over-the-counter kratom products are available as “dietary supplements” in retail stores or online. Although the product packaging sometimes recommends a specific dose, the amount of active ingredients (as well as other agents) is unknown. Kratom is illegal in several states (Box5).
Box
The use and sale of kratom is illegal in several countries, including Australia, Poland, Denmark, Sweden, Malaysia, and Vietnam. In the United States, kratom was legal to grow and purchase in all 50 states until 2015, when the Drug Enforcement Administration (DEA) identified kratom as a “substance of concern.” In August 2016, the DEA submitted a notice of intent to place mitragynine and 7-hydroxymitragynine, 2 alkaloids of kratom that have opioid-like properties, into Schedule I of the Controlled Substance Act; however, due to significant public pressure, the DEA withdrew the request in October 2016.
As of February 2020, kratom was illegal to buy, sell, or use in Wisconsin, Rhode Island, Vermont, Indiana, Arkansas, Alabama, specific counties of some states, and the District of Columbia. Legislation was pending in New York, Missouri, and Louisiana.
Source: Reference 5
The 2 alkaloids of interest
More than 40 alkaloids have been isolated from kratom leaves. The proportions of these alkaloids vary significantly depending on the environment in which the plant is grown, the breeding and harvesting techniques, and the age of the plant.6 Two alkaloids of significant interest are mitragynine (Figure 1) and 7-hydroxymitragynine (Figure 2), both of which are unique to M. speciosa and have opioid-like properties. Administering these alkaloids to morphine-dependent rats resulted in cross-tolerance and precipitated withdrawal when the rats were given naloxone.7 The potency of kratom at the mu opioid receptor has been found to exceed that of morphine.
Competitive binding studies that examined the affinity of mitragynine and 7-hydroxymitragynine at the various opioid receptor subtypes found a preference for the kappa receptors (antagonism), followed by mu (partial agonism), and lastly delta. This profile of mitragynine is very similar to that of buprenorphine.8 The affinity of 7-hydroxymitragynine for the mu receptor (agonism) is significantly greater than that of mitragynine.9 Mitragynine also interacts with noradrenergic and serotonergic pathways by stimulating postsynaptic alpha-2 adrenergic receptors and inhibiting 5-HT2A receptors.9 These properties are responsible for kratom’s ability to manage opioid withdrawal symptoms, which are generally attributed to a hyperactive noradrenergic system. There also is evidence that the hepatic metabolite 7-hydroxymitragynine is important in mediating the analgesic component of mitragynine.10
The initial effects of kratom typically begin within 10 to 20 minutes of consumption, and the full effects are experienced in 30 to 60 minutes.1 The half-life of mitragynine in humans has not yet been determined, but is believed to be relatively short.11 In rats, the half-life of mitragynine is 2 to 3 hours.12 Individuals who use kratom to prevent opioid withdrawal have reported taking it as often as every 6 to 12 hours.13
Continue to: Metabolism of mitragynine...
Metabolism of mitragynine is predominantly carried out through cytochrome P450 (CYP) 3A4, with minor contributions by 2D6 and 2C9. A total of 13 metabolites are produced, including 7-hydroxymitragynine.14 Kratom’s constituents also interact with the CYP system, inhibiting 2C9, 2D6, and 3A4 isoenzymes, and to some extent, 1A2.
Adverse effects can be fatal
An animal study revealed that when administered intravenously, mitragynine and 7-hydroxymitragynine have a similar toxicity profile to heroin.15 When these alkaloids were administered in ascending doses, increases in blood pressure and elevations in liver function tests and creatinine levels from baseline were observed.
Chronic kratom use can result in weight loss, insomnia, constipation, dehydration, skin hyperpigmentation, and extreme fatigue.16 There have also been reports of seizures, delusions, hallucinations, respiratory depression, hepatotoxicity, coma, and death.17,18 An emerging concern is the potential development of fatty liver infiltrates leading to cholestatic liver damage.19-25 One case report described a young man who developed a serum aspartate aminotransferase level of 1,300 IU/L (reference range: 5 to 45 IU/L) and a serum alanine aminotransaminase level of 3,700 IU/L (reference range: 5 to 60 IU/L) after he ingested a kratom product.26 Histologically, the pattern of liver injury mimics primary biliary cholangitis.27
In recent years, calls to poison control centers in the United States related to kratom exposure have risen. Between 2011 and 2017, the number of calls increased from 1 a month to 2 each day.28 The US National Poison Data System has also noted an increase in the number of calls in reference to kratom. It received 2,312 calls from January 2011 through July 2018, with 18 calls occurring in 2011, and 357 within the first 7 months of 2018.29
As of February 2018, the FDA had received reports of 44 deaths associated with kratom.30 There have been reports of fatal overdoses involving kratom, particularly when kratom is co-ingested or used with adulterated and/or combination agents, including one case that involved quetiapine.31-33 There have been reports of deaths believed to be attributed to the use of kratom alone; in one such case, a 35-year-old man experienced a fatal cardiac arrest due to kratom use with no other coingestants.34 Among the reports of deaths in which kratom was the only substance consumed, the mitragynine blood levels of the deceased individuals were found to be higher than the levels associated with individuals who had consumed traditional kratom teas.29
Continue to: There is a lack of quality control...
There is a lack of quality control of commercially available kratom preparations. The FDA has found kratom products that exceeded the level of safe exposure to nickel and lead.35 There have also been reports of Salmonella outbreaks associated with kratom products.36
Detecting kratom use
Mitragynine is a lipophilic alkaloid that is poorly soluble in water37 and eliminated primarily in urine.12 Based on data from treatment center admissions, kratom can be detected in urine samples for 5 to 6 days after use.24,38,39 However, kratom is not detectable by a standard urine toxicology screen; therefore, a high degree of suspicion and special confirmatory testing are necessary. The breakdown products of mitragynine can be detected through gas chromatography coupled with mass spectrometry (GC/MS), liquid chromatography with linear ion trap mass spectrometry, or electrospray tandem mass spectrometry.40-42
A familiar withdrawal syndrome
Abrupt discontinuation of high-dose, long-term kratom use can produce withdrawal symptoms.13 Symptoms of kratom withdrawal resemble those of opioid withdrawal. These include physiological symptoms (mydriasis, nausea, sweating and chills, muscle and body aches, tremors and twitches, diarrhea, rhinorrhea, and lacrimation) and psychological symptoms (insomnia, restlessness, irritability/hostility, fatigue, anxiety, mood disturbances, and hallucinations).13 Symptoms are first noted starting 12 hours after the last use of kratom, and can last up to 7 days.43 Withdrawal intensity has been positively correlated with the daily amount of kratom consumed, as well as the duration and frequency of use.13,16
In 2 case reports, the newborns of women who used kratom during pregnancy experienced neonatal abstinence syndrome.44,45 In these 2 reports, symptoms such as jitteriness, irritability, feeding intolerance, and vomiting emerged on postpartum Day 2. The newborns were admitted to a neonatal ICU and started on a standard opioid protocol with IV morphine and subsequently tapered with an oral formulation over 5 days.44,45
Helping patients who use kratom
The best approach to treating a patient who is experiencing kratom withdrawal is symptomatic management, as would be appropriate for a patient experiencing opioid withdrawal.13 However, the use of agents such as methadone or buprenorphine for patients undergoing kratom withdrawal has not been thoroughly evaluated; very few reports have been published.46,47
Continue to: Similarly, while the standard of care...
Similarly, while the standard of care for treating a patient with opioid use disorder is medication-assisted treatment in combination with counseling and behavioral therapies, there is little evidence on the efficacy of such treatments for patients who use kratom. There are no specific guidelines, and the risk of relapsing to kratom use is high.48,49 Nonetheless, some clinicians have used the same protocol for patients with opioid use disorder to treat patients using kratom, and several published case reports describe this approach.50,51 Because administering buprenorphine/naltrexone to a patient who is dependent on kratom can precipitate withdrawal, clinicians should follow a similar initiation protocol as for opioid dependence when starting a patient on these agents (ie, a washout period with a challenge test would be prudent prior to starting naltrexone).
In cases of kratom overdose, naloxone has been shown to reverse the analgesic effects of mitragynine in rats. However, in a case report of an individual who accidently overdosed on a kratom product, naloxone had a modest effect.52
Bottom Line
Kratom is a botanical substance that acts like a stimulant at low doses and an opioid at higher doses. Patients might use it to treat mood-related symptoms, relieve pain, or manage opioid withdrawal. Kratom use has been associated with the development of addiction as well as a multitude of serious adverse effects, including hepatotoxicity and overdose. Long-term management may be required for a patient who uses kratom.
Related Resources
- White CM. Pharmacologic and clinical assessment of kratom: an update. Am J Health Syst Pharm. 2019;76(23):1915-1925.
- Smith KE, Lawson T. Prevalence and motivations for kratom use in a sample of substance users enrolled in a residential treatment program. Drug Alcohol Depend. 2017;180:340-348.
Drug Brand Names
Buprenorphine • Subutex, Sublocade
Buprenorphine/naltrexone • Suboxone
Methadone • Methadose
Naltrexone • Revia
Naloxone • Narcan
Quetiapine • Seroquel
1. Henningfield JE, Fant RV, Wang DW. The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research. Psychopharmacology (Berl). 2018;235(2):573-589.
2. Chang-Chien GC, Odonkor CA, Amorapanth P, et al. Is kratom the new ‘legal high’ on the block?: the case of an emerging opioid receptor agonist with substance abuse potential. Pain Physician. 2017;20(1):E195-E198.
3. Penders T, Jones WB. Kratom, a substance of increasing concern [PCSS webinar]. Providers Clinical Support System. November 28, 2018. https://pcssnow.org/event/kratom-a-substance-of-increasing-concern. Accessed January 29, 2020.
4. Grundmann O. Patterns of kratom use and health impact in the US-results from an online survey. Drug Alcohol Depend. 2017;176:63-70.
5. US Drug Enforcement Administration. Drugs of concern. https://www.dea.gov/sites/default/files/sites/getsmartaboutdrugs.com/files/publications/DoA_2017Ed_Updated_6.16.17.pdf#page=84. Updated June 16, 2017. Accessed January 29, 2020.
6. Matsumoto K, Horie S, Ishikawa H, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sciences. 2004;74(17):2143-2155.
7. Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull (Tokyo). 2004;52(8):916-928.
8. Suhaimi FW, Yusoff NH, Hassan R, et al. Neurobiology of kratom and its main alkaloid mitragynine. Brain Res Bull. 2016;126(pt 1):29-40.
9. Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012;112(12):792-799.
10. Kruegel AC, Uprety R, Grinnell SG, et al. 7-hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. ACS Cent Sci. 2019;5(6):992-1001.
11. Trakulsrichai S, Sathirakul K, Auparakkitanon S, et al. Pharmacokinetics of mitragynine in man. Drug Des Devel Ther. 2015:9:2421-2429.
12. Warner ML, Kaufman NC, Grundmann O, et al. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Intl J Legal Med. 2016;130(1):127-138.
13. Stanciu CN, Gnanasegaram SA, Ahmed S, et al. Kratom withdrawal: a systematic review with case series. J Psychoactive Drugs. 2019;51(1):12-18.
14. Kamble SH, Sharma A, King TI, et al. Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom). Xenobiotica. 2019;49(11):1279-1288.
15. Smith LC, Lin L, Hwang CS, et al. Lateral flow assessment and unanticipated toxicity of kratom. Chem Res Toxicol. 2019;32(1):113-121.
16. Saingam D, Assanangkornchai S, Geater AF, et al. Factor analytical investigation of Krathom (Mitragyna speciosa Korth.) withdrawal syndrome in Thailand. J Psychoactive Drugs. 2016;48(2):76-85.
17. Vicknasingam B, Narayanan S, Beng GT, et al. The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. Int J Drug Policy. 2010;21(4):283-288.
18. Saingam D, Assanangkornchai S, Geater AF, et al. Pattern and consequences of krathom (Mitragyna speciosa Korth.) use among male villagers in southern Thailand: a qualitative study. Int J Drug Policy. 2013;24(4):351-358.
19. Fernandes CT, Iqbal U, Tighe SP, et al. Kratom-induced cholestatic liver injury and its conservative management. J Investig Med High Impact Case Rep. 2019;7:2324709619836138. doi: 10.1177/2324709619836138.
20. Dorman C, Wong M, Khan A. Cholestatic hepatitis from prolonged kratom use: a case report. Hepatology. 2015;61(3):1086-1087.
21. Osborne CS, Overstreet AN, Rockey DC, et al. Drug-induced liver injury caused by kratom use as an alternative pain treatment amid an ongoing opioid epidemic. J Investig Med High Impact Case Rep. 2019;7:2324709619826167. doi: 10.1177/2324709619826167.
22. Mousa MS, Sephien A, Gutierrez J, et al. N-acetylcysteine for acute hepatitis induced by kratom herbal tea. Am J Ther. 2018;25(5):e550-e551.
23. Riverso M, Chang M, Soldevila-Pico C, et al. Histologic characterization of kratom use-associated liver injury. Gastroenterology Res. 2018;11(1):79-82.
24. Kapp FG, Maurer HH, Auwärter V, et al. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol. 2011;7(3):227-231.
25. Antony A, Lee TP. Herb-induced liver injury with cholestasis and renal injury secondary to short-term use of kratom (Mitragyna speciosa). Am J Ther. 2019;26(4):e546-e547.
26. Palasamudram Shekar S, Rojas EE, D’Angelo CC, et al. Legally lethal kratom: a herbal supplement with overdose potential. J Psychoactive Drugs. 2019;51(1):28-30.
27. Aldyab M, Ells PF, Bui R, et al. Kratom-induced cholestatic liver injury mimicking anti-mitochondrial antibody-negative primary biliary cholangitis: a case report and review of literature. Gastroenterology Res. 2019;12(4):211-215.
28. Post S, Spiller HA, Chounthirath T. Kratom exposures reported to United States poison control centers: 2011-2017. Clinical Toxicol (Phila). 2019;57(10):847-854.
29. Eggleston W, Stoppacher R, Suen K, et al. Kratom use and toxicities in the United States. Pharmacotherapy. 2019;39(7):775-777.
30. US Food & Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom , underscoring its potential for abuse. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-scientific-evidence-presence-opioid-compounds. Published February 6, 2019. Accessed January 29, 2020.
31. Gershman K, Timm K, Frank M, et al. Deaths in Colorado attributed to kratom. N Engl J Med. 2019;380(1):97-98.
32. Kronstrand R, Roman M, Thelander G, et al. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend krypton. J Anal Toxicol. 2011;35(4):242-247.
33. Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019;15(1):110-113.
34. Abdullah HMA, Haq I, Lamfers R. Cardiac arrest in a young healthy male patient secondary to kratom ingestion: is this ‘legal high’ substance more dangerous than initially thought? BMJ Case Rep. 2019;12(7):pii: e229778. doi: 10.1136/bcr-2019-229778.
35. Laboratory analysis of kratom products for heavy metals. US FDA. https://www.fda.gov/news-events/public-health-focus/laboratory-analysis-kratom-products-heavy-metals. Updated April 3, 2019. Accessed January 29, 2020.
36. FDA investigated multistate outbreak of salmonella infections linked to products reported to contain kratom. US FDA. https://www.fda.gov/food/outbreaks-foodborne-illness/fda-investigated-multistate-outbreak-salmonella-infections-linked-products-reported-contain-kratom. Updated June 29, 2018. Accessed January 14, 2020.
37. Aggarwal G, Robertson E, McKinlay J, et a., Death from kratom toxicity and the possible role of intralipid. J Intensive Care Soc. 2018;19(1):61-63.
38. Drug Facts. Kratom. Confirm Biosciences. https://www.confirmbiosciences.com/knowledge/drug-facts/kratom/. Accessed January 14, 2020.
39. Grinspoon P. How long does kratom stay in the system? Addiction Resource. https://addictionresource.com/drugs/kratom/how-long-kratom-stay-in-your-system/. Updated December 18, 2019. Accessed January 29, 2020.
40. Kaewklum D, Kaewklum M, Pootrakronchai R, et al. Detection of mitragynine and its metaboilite in urine following ingestion of leaves of Mitragyna speciosa korth. Recent Advances in Doping Analysis (13). Proceedings of the Manfred Donike Workshop, 23rd Cologne Workshop on Dope Analysis. 2005:403-406.
41. Lu S, Tran BN, Nelsen JL, et al. Quantitative analysis of mitragynine in human urine by high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(24):2499-2505.
42. Philipp AA, Wissenbach DK, Zoerntlein SW, et al. Studies on the metabolism of mitragynine, the main alkaloid of the herbal drug kratom, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry. J Mass Spectrom. 2009;44(8):1249-1261.
43. Manda VK, Bharathi A, Ali Z, et al. Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline. Planta Med. 2014;80(7):568-576.
44. Davidson L, Rawat M, Stojanovski S, et al. Natural drugs, not so natural effects: neonatal abstinence syndrome secondary to ‘kratom‘. J Neonatal Perinatal Med. 2019;12(1):109-112.
45. Mackay L, Abrahams R. Novel case of maternal and neonatal kratom dependence and withdrawal. Can Fam Physician. 2018;64(2):121-122.
46. McWhirter L, Morris S. A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence. Eur Addict Res. 2010;16(4):229-231.
47. Galbis-Reig David. A case report of kratom addiction and withdrawal. WMJ. 2016;115(1):49-52; quiz 53.
48. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciose) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend. 2014;139:132-137.
49. Singh D, Müller CP, Vicknasingam, et al. Social functioning of kratom (Mitragyna speciosa) users in Malaysia. J Psychoactive Drugs. 2015;47(2):125-131.
50. Khazaeli A, Jerry JM, Vazirian M. Treatment of kratom withdrawal and addiction with buprenorphine. J Addict Med. 2018;12(6):493-495.
51. Buresh M. Treatment of kratom dependence with buprenorphine-naloxone maintenance. J Addict Med. 2018;12(6):481-483.
52. Overbeek DL, Abraham J, Munzer BW. Kratom (mitragynine) ingestion requiring naloxone reversal. Clin Pract Cases Emerg Med. 2019;3(1):24-26.
Mitragyna speciosa, better known as kratom, is a tropical evergreen tree that is native to Southeast Asia. Botanically, it is a member of the Rubiaceae family, as is the coffee plant, and physical laborers among indigenous populations have historically chewed the leaves or brewed them as a tea to improve endurance and reduce fatigue.1 Kratom is psychoactive; small amounts (up to 5 g of plant material) possess stimulant properties, while larger doses (>5 g) produce opioid-like, sedative, euphoric, and antinociceptive effects.2
In recent years, kratom has gained popularity in Western parts of the world due to its unique properties and perceived safety as a botanical product. Individuals may use kratom to boost their energy, relieve pain, or treat a wide range of physical or mood problems. Increasingly, kratom is being used by people who abuse opioids to self-manage opioid withdrawal, or for its euphoric effects. But kratom carries several important risks, including addiction, serious adverse effects, and possibly death. In this article, we review the epidemiology and pharmacology of kratom, and provide some guidance for educating patients about this substance.
Widely used but not FDA approved
Although kratom is not regulated or approved by the FDA, 3 to 5 million Americans use it regularly.3 According to an internet survey, kratom users are mostly college-educated, employed white men, age 31 to 50, who take the substance to manage pain or to treat general anxiety and mood disorders.4 Some individuals use kratom as an opioid substitute to reduce symptoms of opioid withdrawal.4
Kratom is available from a wide range of manufacturers in various formulations, including powders, tablets, liquids, and gum. It is sometimes sold in combination with other agents as a single product. Low-cost, over-the-counter kratom products are available as “dietary supplements” in retail stores or online. Although the product packaging sometimes recommends a specific dose, the amount of active ingredients (as well as other agents) is unknown. Kratom is illegal in several states (Box5).
Box
The use and sale of kratom is illegal in several countries, including Australia, Poland, Denmark, Sweden, Malaysia, and Vietnam. In the United States, kratom was legal to grow and purchase in all 50 states until 2015, when the Drug Enforcement Administration (DEA) identified kratom as a “substance of concern.” In August 2016, the DEA submitted a notice of intent to place mitragynine and 7-hydroxymitragynine, 2 alkaloids of kratom that have opioid-like properties, into Schedule I of the Controlled Substance Act; however, due to significant public pressure, the DEA withdrew the request in October 2016.
As of February 2020, kratom was illegal to buy, sell, or use in Wisconsin, Rhode Island, Vermont, Indiana, Arkansas, Alabama, specific counties of some states, and the District of Columbia. Legislation was pending in New York, Missouri, and Louisiana.
Source: Reference 5
The 2 alkaloids of interest
More than 40 alkaloids have been isolated from kratom leaves. The proportions of these alkaloids vary significantly depending on the environment in which the plant is grown, the breeding and harvesting techniques, and the age of the plant.6 Two alkaloids of significant interest are mitragynine (Figure 1) and 7-hydroxymitragynine (Figure 2), both of which are unique to M. speciosa and have opioid-like properties. Administering these alkaloids to morphine-dependent rats resulted in cross-tolerance and precipitated withdrawal when the rats were given naloxone.7 The potency of kratom at the mu opioid receptor has been found to exceed that of morphine.
Competitive binding studies that examined the affinity of mitragynine and 7-hydroxymitragynine at the various opioid receptor subtypes found a preference for the kappa receptors (antagonism), followed by mu (partial agonism), and lastly delta. This profile of mitragynine is very similar to that of buprenorphine.8 The affinity of 7-hydroxymitragynine for the mu receptor (agonism) is significantly greater than that of mitragynine.9 Mitragynine also interacts with noradrenergic and serotonergic pathways by stimulating postsynaptic alpha-2 adrenergic receptors and inhibiting 5-HT2A receptors.9 These properties are responsible for kratom’s ability to manage opioid withdrawal symptoms, which are generally attributed to a hyperactive noradrenergic system. There also is evidence that the hepatic metabolite 7-hydroxymitragynine is important in mediating the analgesic component of mitragynine.10
The initial effects of kratom typically begin within 10 to 20 minutes of consumption, and the full effects are experienced in 30 to 60 minutes.1 The half-life of mitragynine in humans has not yet been determined, but is believed to be relatively short.11 In rats, the half-life of mitragynine is 2 to 3 hours.12 Individuals who use kratom to prevent opioid withdrawal have reported taking it as often as every 6 to 12 hours.13
Continue to: Metabolism of mitragynine...
Metabolism of mitragynine is predominantly carried out through cytochrome P450 (CYP) 3A4, with minor contributions by 2D6 and 2C9. A total of 13 metabolites are produced, including 7-hydroxymitragynine.14 Kratom’s constituents also interact with the CYP system, inhibiting 2C9, 2D6, and 3A4 isoenzymes, and to some extent, 1A2.
Adverse effects can be fatal
An animal study revealed that when administered intravenously, mitragynine and 7-hydroxymitragynine have a similar toxicity profile to heroin.15 When these alkaloids were administered in ascending doses, increases in blood pressure and elevations in liver function tests and creatinine levels from baseline were observed.
Chronic kratom use can result in weight loss, insomnia, constipation, dehydration, skin hyperpigmentation, and extreme fatigue.16 There have also been reports of seizures, delusions, hallucinations, respiratory depression, hepatotoxicity, coma, and death.17,18 An emerging concern is the potential development of fatty liver infiltrates leading to cholestatic liver damage.19-25 One case report described a young man who developed a serum aspartate aminotransferase level of 1,300 IU/L (reference range: 5 to 45 IU/L) and a serum alanine aminotransaminase level of 3,700 IU/L (reference range: 5 to 60 IU/L) after he ingested a kratom product.26 Histologically, the pattern of liver injury mimics primary biliary cholangitis.27
In recent years, calls to poison control centers in the United States related to kratom exposure have risen. Between 2011 and 2017, the number of calls increased from 1 a month to 2 each day.28 The US National Poison Data System has also noted an increase in the number of calls in reference to kratom. It received 2,312 calls from January 2011 through July 2018, with 18 calls occurring in 2011, and 357 within the first 7 months of 2018.29
As of February 2018, the FDA had received reports of 44 deaths associated with kratom.30 There have been reports of fatal overdoses involving kratom, particularly when kratom is co-ingested or used with adulterated and/or combination agents, including one case that involved quetiapine.31-33 There have been reports of deaths believed to be attributed to the use of kratom alone; in one such case, a 35-year-old man experienced a fatal cardiac arrest due to kratom use with no other coingestants.34 Among the reports of deaths in which kratom was the only substance consumed, the mitragynine blood levels of the deceased individuals were found to be higher than the levels associated with individuals who had consumed traditional kratom teas.29
Continue to: There is a lack of quality control...
There is a lack of quality control of commercially available kratom preparations. The FDA has found kratom products that exceeded the level of safe exposure to nickel and lead.35 There have also been reports of Salmonella outbreaks associated with kratom products.36
Detecting kratom use
Mitragynine is a lipophilic alkaloid that is poorly soluble in water37 and eliminated primarily in urine.12 Based on data from treatment center admissions, kratom can be detected in urine samples for 5 to 6 days after use.24,38,39 However, kratom is not detectable by a standard urine toxicology screen; therefore, a high degree of suspicion and special confirmatory testing are necessary. The breakdown products of mitragynine can be detected through gas chromatography coupled with mass spectrometry (GC/MS), liquid chromatography with linear ion trap mass spectrometry, or electrospray tandem mass spectrometry.40-42
A familiar withdrawal syndrome
Abrupt discontinuation of high-dose, long-term kratom use can produce withdrawal symptoms.13 Symptoms of kratom withdrawal resemble those of opioid withdrawal. These include physiological symptoms (mydriasis, nausea, sweating and chills, muscle and body aches, tremors and twitches, diarrhea, rhinorrhea, and lacrimation) and psychological symptoms (insomnia, restlessness, irritability/hostility, fatigue, anxiety, mood disturbances, and hallucinations).13 Symptoms are first noted starting 12 hours after the last use of kratom, and can last up to 7 days.43 Withdrawal intensity has been positively correlated with the daily amount of kratom consumed, as well as the duration and frequency of use.13,16
In 2 case reports, the newborns of women who used kratom during pregnancy experienced neonatal abstinence syndrome.44,45 In these 2 reports, symptoms such as jitteriness, irritability, feeding intolerance, and vomiting emerged on postpartum Day 2. The newborns were admitted to a neonatal ICU and started on a standard opioid protocol with IV morphine and subsequently tapered with an oral formulation over 5 days.44,45
Helping patients who use kratom
The best approach to treating a patient who is experiencing kratom withdrawal is symptomatic management, as would be appropriate for a patient experiencing opioid withdrawal.13 However, the use of agents such as methadone or buprenorphine for patients undergoing kratom withdrawal has not been thoroughly evaluated; very few reports have been published.46,47
Continue to: Similarly, while the standard of care...
Similarly, while the standard of care for treating a patient with opioid use disorder is medication-assisted treatment in combination with counseling and behavioral therapies, there is little evidence on the efficacy of such treatments for patients who use kratom. There are no specific guidelines, and the risk of relapsing to kratom use is high.48,49 Nonetheless, some clinicians have used the same protocol for patients with opioid use disorder to treat patients using kratom, and several published case reports describe this approach.50,51 Because administering buprenorphine/naltrexone to a patient who is dependent on kratom can precipitate withdrawal, clinicians should follow a similar initiation protocol as for opioid dependence when starting a patient on these agents (ie, a washout period with a challenge test would be prudent prior to starting naltrexone).
In cases of kratom overdose, naloxone has been shown to reverse the analgesic effects of mitragynine in rats. However, in a case report of an individual who accidently overdosed on a kratom product, naloxone had a modest effect.52
Bottom Line
Kratom is a botanical substance that acts like a stimulant at low doses and an opioid at higher doses. Patients might use it to treat mood-related symptoms, relieve pain, or manage opioid withdrawal. Kratom use has been associated with the development of addiction as well as a multitude of serious adverse effects, including hepatotoxicity and overdose. Long-term management may be required for a patient who uses kratom.
Related Resources
- White CM. Pharmacologic and clinical assessment of kratom: an update. Am J Health Syst Pharm. 2019;76(23):1915-1925.
- Smith KE, Lawson T. Prevalence and motivations for kratom use in a sample of substance users enrolled in a residential treatment program. Drug Alcohol Depend. 2017;180:340-348.
Drug Brand Names
Buprenorphine • Subutex, Sublocade
Buprenorphine/naltrexone • Suboxone
Methadone • Methadose
Naltrexone • Revia
Naloxone • Narcan
Quetiapine • Seroquel
Mitragyna speciosa, better known as kratom, is a tropical evergreen tree that is native to Southeast Asia. Botanically, it is a member of the Rubiaceae family, as is the coffee plant, and physical laborers among indigenous populations have historically chewed the leaves or brewed them as a tea to improve endurance and reduce fatigue.1 Kratom is psychoactive; small amounts (up to 5 g of plant material) possess stimulant properties, while larger doses (>5 g) produce opioid-like, sedative, euphoric, and antinociceptive effects.2
In recent years, kratom has gained popularity in Western parts of the world due to its unique properties and perceived safety as a botanical product. Individuals may use kratom to boost their energy, relieve pain, or treat a wide range of physical or mood problems. Increasingly, kratom is being used by people who abuse opioids to self-manage opioid withdrawal, or for its euphoric effects. But kratom carries several important risks, including addiction, serious adverse effects, and possibly death. In this article, we review the epidemiology and pharmacology of kratom, and provide some guidance for educating patients about this substance.
Widely used but not FDA approved
Although kratom is not regulated or approved by the FDA, 3 to 5 million Americans use it regularly.3 According to an internet survey, kratom users are mostly college-educated, employed white men, age 31 to 50, who take the substance to manage pain or to treat general anxiety and mood disorders.4 Some individuals use kratom as an opioid substitute to reduce symptoms of opioid withdrawal.4
Kratom is available from a wide range of manufacturers in various formulations, including powders, tablets, liquids, and gum. It is sometimes sold in combination with other agents as a single product. Low-cost, over-the-counter kratom products are available as “dietary supplements” in retail stores or online. Although the product packaging sometimes recommends a specific dose, the amount of active ingredients (as well as other agents) is unknown. Kratom is illegal in several states (Box5).
Box
The use and sale of kratom is illegal in several countries, including Australia, Poland, Denmark, Sweden, Malaysia, and Vietnam. In the United States, kratom was legal to grow and purchase in all 50 states until 2015, when the Drug Enforcement Administration (DEA) identified kratom as a “substance of concern.” In August 2016, the DEA submitted a notice of intent to place mitragynine and 7-hydroxymitragynine, 2 alkaloids of kratom that have opioid-like properties, into Schedule I of the Controlled Substance Act; however, due to significant public pressure, the DEA withdrew the request in October 2016.
As of February 2020, kratom was illegal to buy, sell, or use in Wisconsin, Rhode Island, Vermont, Indiana, Arkansas, Alabama, specific counties of some states, and the District of Columbia. Legislation was pending in New York, Missouri, and Louisiana.
Source: Reference 5
The 2 alkaloids of interest
More than 40 alkaloids have been isolated from kratom leaves. The proportions of these alkaloids vary significantly depending on the environment in which the plant is grown, the breeding and harvesting techniques, and the age of the plant.6 Two alkaloids of significant interest are mitragynine (Figure 1) and 7-hydroxymitragynine (Figure 2), both of which are unique to M. speciosa and have opioid-like properties. Administering these alkaloids to morphine-dependent rats resulted in cross-tolerance and precipitated withdrawal when the rats were given naloxone.7 The potency of kratom at the mu opioid receptor has been found to exceed that of morphine.
Competitive binding studies that examined the affinity of mitragynine and 7-hydroxymitragynine at the various opioid receptor subtypes found a preference for the kappa receptors (antagonism), followed by mu (partial agonism), and lastly delta. This profile of mitragynine is very similar to that of buprenorphine.8 The affinity of 7-hydroxymitragynine for the mu receptor (agonism) is significantly greater than that of mitragynine.9 Mitragynine also interacts with noradrenergic and serotonergic pathways by stimulating postsynaptic alpha-2 adrenergic receptors and inhibiting 5-HT2A receptors.9 These properties are responsible for kratom’s ability to manage opioid withdrawal symptoms, which are generally attributed to a hyperactive noradrenergic system. There also is evidence that the hepatic metabolite 7-hydroxymitragynine is important in mediating the analgesic component of mitragynine.10
The initial effects of kratom typically begin within 10 to 20 minutes of consumption, and the full effects are experienced in 30 to 60 minutes.1 The half-life of mitragynine in humans has not yet been determined, but is believed to be relatively short.11 In rats, the half-life of mitragynine is 2 to 3 hours.12 Individuals who use kratom to prevent opioid withdrawal have reported taking it as often as every 6 to 12 hours.13
Continue to: Metabolism of mitragynine...
Metabolism of mitragynine is predominantly carried out through cytochrome P450 (CYP) 3A4, with minor contributions by 2D6 and 2C9. A total of 13 metabolites are produced, including 7-hydroxymitragynine.14 Kratom’s constituents also interact with the CYP system, inhibiting 2C9, 2D6, and 3A4 isoenzymes, and to some extent, 1A2.
Adverse effects can be fatal
An animal study revealed that when administered intravenously, mitragynine and 7-hydroxymitragynine have a similar toxicity profile to heroin.15 When these alkaloids were administered in ascending doses, increases in blood pressure and elevations in liver function tests and creatinine levels from baseline were observed.
Chronic kratom use can result in weight loss, insomnia, constipation, dehydration, skin hyperpigmentation, and extreme fatigue.16 There have also been reports of seizures, delusions, hallucinations, respiratory depression, hepatotoxicity, coma, and death.17,18 An emerging concern is the potential development of fatty liver infiltrates leading to cholestatic liver damage.19-25 One case report described a young man who developed a serum aspartate aminotransferase level of 1,300 IU/L (reference range: 5 to 45 IU/L) and a serum alanine aminotransaminase level of 3,700 IU/L (reference range: 5 to 60 IU/L) after he ingested a kratom product.26 Histologically, the pattern of liver injury mimics primary biliary cholangitis.27
In recent years, calls to poison control centers in the United States related to kratom exposure have risen. Between 2011 and 2017, the number of calls increased from 1 a month to 2 each day.28 The US National Poison Data System has also noted an increase in the number of calls in reference to kratom. It received 2,312 calls from January 2011 through July 2018, with 18 calls occurring in 2011, and 357 within the first 7 months of 2018.29
As of February 2018, the FDA had received reports of 44 deaths associated with kratom.30 There have been reports of fatal overdoses involving kratom, particularly when kratom is co-ingested or used with adulterated and/or combination agents, including one case that involved quetiapine.31-33 There have been reports of deaths believed to be attributed to the use of kratom alone; in one such case, a 35-year-old man experienced a fatal cardiac arrest due to kratom use with no other coingestants.34 Among the reports of deaths in which kratom was the only substance consumed, the mitragynine blood levels of the deceased individuals were found to be higher than the levels associated with individuals who had consumed traditional kratom teas.29
Continue to: There is a lack of quality control...
There is a lack of quality control of commercially available kratom preparations. The FDA has found kratom products that exceeded the level of safe exposure to nickel and lead.35 There have also been reports of Salmonella outbreaks associated with kratom products.36
Detecting kratom use
Mitragynine is a lipophilic alkaloid that is poorly soluble in water37 and eliminated primarily in urine.12 Based on data from treatment center admissions, kratom can be detected in urine samples for 5 to 6 days after use.24,38,39 However, kratom is not detectable by a standard urine toxicology screen; therefore, a high degree of suspicion and special confirmatory testing are necessary. The breakdown products of mitragynine can be detected through gas chromatography coupled with mass spectrometry (GC/MS), liquid chromatography with linear ion trap mass spectrometry, or electrospray tandem mass spectrometry.40-42
A familiar withdrawal syndrome
Abrupt discontinuation of high-dose, long-term kratom use can produce withdrawal symptoms.13 Symptoms of kratom withdrawal resemble those of opioid withdrawal. These include physiological symptoms (mydriasis, nausea, sweating and chills, muscle and body aches, tremors and twitches, diarrhea, rhinorrhea, and lacrimation) and psychological symptoms (insomnia, restlessness, irritability/hostility, fatigue, anxiety, mood disturbances, and hallucinations).13 Symptoms are first noted starting 12 hours after the last use of kratom, and can last up to 7 days.43 Withdrawal intensity has been positively correlated with the daily amount of kratom consumed, as well as the duration and frequency of use.13,16
In 2 case reports, the newborns of women who used kratom during pregnancy experienced neonatal abstinence syndrome.44,45 In these 2 reports, symptoms such as jitteriness, irritability, feeding intolerance, and vomiting emerged on postpartum Day 2. The newborns were admitted to a neonatal ICU and started on a standard opioid protocol with IV morphine and subsequently tapered with an oral formulation over 5 days.44,45
Helping patients who use kratom
The best approach to treating a patient who is experiencing kratom withdrawal is symptomatic management, as would be appropriate for a patient experiencing opioid withdrawal.13 However, the use of agents such as methadone or buprenorphine for patients undergoing kratom withdrawal has not been thoroughly evaluated; very few reports have been published.46,47
Continue to: Similarly, while the standard of care...
Similarly, while the standard of care for treating a patient with opioid use disorder is medication-assisted treatment in combination with counseling and behavioral therapies, there is little evidence on the efficacy of such treatments for patients who use kratom. There are no specific guidelines, and the risk of relapsing to kratom use is high.48,49 Nonetheless, some clinicians have used the same protocol for patients with opioid use disorder to treat patients using kratom, and several published case reports describe this approach.50,51 Because administering buprenorphine/naltrexone to a patient who is dependent on kratom can precipitate withdrawal, clinicians should follow a similar initiation protocol as for opioid dependence when starting a patient on these agents (ie, a washout period with a challenge test would be prudent prior to starting naltrexone).
In cases of kratom overdose, naloxone has been shown to reverse the analgesic effects of mitragynine in rats. However, in a case report of an individual who accidently overdosed on a kratom product, naloxone had a modest effect.52
Bottom Line
Kratom is a botanical substance that acts like a stimulant at low doses and an opioid at higher doses. Patients might use it to treat mood-related symptoms, relieve pain, or manage opioid withdrawal. Kratom use has been associated with the development of addiction as well as a multitude of serious adverse effects, including hepatotoxicity and overdose. Long-term management may be required for a patient who uses kratom.
Related Resources
- White CM. Pharmacologic and clinical assessment of kratom: an update. Am J Health Syst Pharm. 2019;76(23):1915-1925.
- Smith KE, Lawson T. Prevalence and motivations for kratom use in a sample of substance users enrolled in a residential treatment program. Drug Alcohol Depend. 2017;180:340-348.
Drug Brand Names
Buprenorphine • Subutex, Sublocade
Buprenorphine/naltrexone • Suboxone
Methadone • Methadose
Naltrexone • Revia
Naloxone • Narcan
Quetiapine • Seroquel
1. Henningfield JE, Fant RV, Wang DW. The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research. Psychopharmacology (Berl). 2018;235(2):573-589.
2. Chang-Chien GC, Odonkor CA, Amorapanth P, et al. Is kratom the new ‘legal high’ on the block?: the case of an emerging opioid receptor agonist with substance abuse potential. Pain Physician. 2017;20(1):E195-E198.
3. Penders T, Jones WB. Kratom, a substance of increasing concern [PCSS webinar]. Providers Clinical Support System. November 28, 2018. https://pcssnow.org/event/kratom-a-substance-of-increasing-concern. Accessed January 29, 2020.
4. Grundmann O. Patterns of kratom use and health impact in the US-results from an online survey. Drug Alcohol Depend. 2017;176:63-70.
5. US Drug Enforcement Administration. Drugs of concern. https://www.dea.gov/sites/default/files/sites/getsmartaboutdrugs.com/files/publications/DoA_2017Ed_Updated_6.16.17.pdf#page=84. Updated June 16, 2017. Accessed January 29, 2020.
6. Matsumoto K, Horie S, Ishikawa H, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sciences. 2004;74(17):2143-2155.
7. Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull (Tokyo). 2004;52(8):916-928.
8. Suhaimi FW, Yusoff NH, Hassan R, et al. Neurobiology of kratom and its main alkaloid mitragynine. Brain Res Bull. 2016;126(pt 1):29-40.
9. Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012;112(12):792-799.
10. Kruegel AC, Uprety R, Grinnell SG, et al. 7-hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. ACS Cent Sci. 2019;5(6):992-1001.
11. Trakulsrichai S, Sathirakul K, Auparakkitanon S, et al. Pharmacokinetics of mitragynine in man. Drug Des Devel Ther. 2015:9:2421-2429.
12. Warner ML, Kaufman NC, Grundmann O, et al. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Intl J Legal Med. 2016;130(1):127-138.
13. Stanciu CN, Gnanasegaram SA, Ahmed S, et al. Kratom withdrawal: a systematic review with case series. J Psychoactive Drugs. 2019;51(1):12-18.
14. Kamble SH, Sharma A, King TI, et al. Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom). Xenobiotica. 2019;49(11):1279-1288.
15. Smith LC, Lin L, Hwang CS, et al. Lateral flow assessment and unanticipated toxicity of kratom. Chem Res Toxicol. 2019;32(1):113-121.
16. Saingam D, Assanangkornchai S, Geater AF, et al. Factor analytical investigation of Krathom (Mitragyna speciosa Korth.) withdrawal syndrome in Thailand. J Psychoactive Drugs. 2016;48(2):76-85.
17. Vicknasingam B, Narayanan S, Beng GT, et al. The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. Int J Drug Policy. 2010;21(4):283-288.
18. Saingam D, Assanangkornchai S, Geater AF, et al. Pattern and consequences of krathom (Mitragyna speciosa Korth.) use among male villagers in southern Thailand: a qualitative study. Int J Drug Policy. 2013;24(4):351-358.
19. Fernandes CT, Iqbal U, Tighe SP, et al. Kratom-induced cholestatic liver injury and its conservative management. J Investig Med High Impact Case Rep. 2019;7:2324709619836138. doi: 10.1177/2324709619836138.
20. Dorman C, Wong M, Khan A. Cholestatic hepatitis from prolonged kratom use: a case report. Hepatology. 2015;61(3):1086-1087.
21. Osborne CS, Overstreet AN, Rockey DC, et al. Drug-induced liver injury caused by kratom use as an alternative pain treatment amid an ongoing opioid epidemic. J Investig Med High Impact Case Rep. 2019;7:2324709619826167. doi: 10.1177/2324709619826167.
22. Mousa MS, Sephien A, Gutierrez J, et al. N-acetylcysteine for acute hepatitis induced by kratom herbal tea. Am J Ther. 2018;25(5):e550-e551.
23. Riverso M, Chang M, Soldevila-Pico C, et al. Histologic characterization of kratom use-associated liver injury. Gastroenterology Res. 2018;11(1):79-82.
24. Kapp FG, Maurer HH, Auwärter V, et al. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol. 2011;7(3):227-231.
25. Antony A, Lee TP. Herb-induced liver injury with cholestasis and renal injury secondary to short-term use of kratom (Mitragyna speciosa). Am J Ther. 2019;26(4):e546-e547.
26. Palasamudram Shekar S, Rojas EE, D’Angelo CC, et al. Legally lethal kratom: a herbal supplement with overdose potential. J Psychoactive Drugs. 2019;51(1):28-30.
27. Aldyab M, Ells PF, Bui R, et al. Kratom-induced cholestatic liver injury mimicking anti-mitochondrial antibody-negative primary biliary cholangitis: a case report and review of literature. Gastroenterology Res. 2019;12(4):211-215.
28. Post S, Spiller HA, Chounthirath T. Kratom exposures reported to United States poison control centers: 2011-2017. Clinical Toxicol (Phila). 2019;57(10):847-854.
29. Eggleston W, Stoppacher R, Suen K, et al. Kratom use and toxicities in the United States. Pharmacotherapy. 2019;39(7):775-777.
30. US Food & Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom , underscoring its potential for abuse. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-scientific-evidence-presence-opioid-compounds. Published February 6, 2019. Accessed January 29, 2020.
31. Gershman K, Timm K, Frank M, et al. Deaths in Colorado attributed to kratom. N Engl J Med. 2019;380(1):97-98.
32. Kronstrand R, Roman M, Thelander G, et al. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend krypton. J Anal Toxicol. 2011;35(4):242-247.
33. Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019;15(1):110-113.
34. Abdullah HMA, Haq I, Lamfers R. Cardiac arrest in a young healthy male patient secondary to kratom ingestion: is this ‘legal high’ substance more dangerous than initially thought? BMJ Case Rep. 2019;12(7):pii: e229778. doi: 10.1136/bcr-2019-229778.
35. Laboratory analysis of kratom products for heavy metals. US FDA. https://www.fda.gov/news-events/public-health-focus/laboratory-analysis-kratom-products-heavy-metals. Updated April 3, 2019. Accessed January 29, 2020.
36. FDA investigated multistate outbreak of salmonella infections linked to products reported to contain kratom. US FDA. https://www.fda.gov/food/outbreaks-foodborne-illness/fda-investigated-multistate-outbreak-salmonella-infections-linked-products-reported-contain-kratom. Updated June 29, 2018. Accessed January 14, 2020.
37. Aggarwal G, Robertson E, McKinlay J, et a., Death from kratom toxicity and the possible role of intralipid. J Intensive Care Soc. 2018;19(1):61-63.
38. Drug Facts. Kratom. Confirm Biosciences. https://www.confirmbiosciences.com/knowledge/drug-facts/kratom/. Accessed January 14, 2020.
39. Grinspoon P. How long does kratom stay in the system? Addiction Resource. https://addictionresource.com/drugs/kratom/how-long-kratom-stay-in-your-system/. Updated December 18, 2019. Accessed January 29, 2020.
40. Kaewklum D, Kaewklum M, Pootrakronchai R, et al. Detection of mitragynine and its metaboilite in urine following ingestion of leaves of Mitragyna speciosa korth. Recent Advances in Doping Analysis (13). Proceedings of the Manfred Donike Workshop, 23rd Cologne Workshop on Dope Analysis. 2005:403-406.
41. Lu S, Tran BN, Nelsen JL, et al. Quantitative analysis of mitragynine in human urine by high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(24):2499-2505.
42. Philipp AA, Wissenbach DK, Zoerntlein SW, et al. Studies on the metabolism of mitragynine, the main alkaloid of the herbal drug kratom, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry. J Mass Spectrom. 2009;44(8):1249-1261.
43. Manda VK, Bharathi A, Ali Z, et al. Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline. Planta Med. 2014;80(7):568-576.
44. Davidson L, Rawat M, Stojanovski S, et al. Natural drugs, not so natural effects: neonatal abstinence syndrome secondary to ‘kratom‘. J Neonatal Perinatal Med. 2019;12(1):109-112.
45. Mackay L, Abrahams R. Novel case of maternal and neonatal kratom dependence and withdrawal. Can Fam Physician. 2018;64(2):121-122.
46. McWhirter L, Morris S. A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence. Eur Addict Res. 2010;16(4):229-231.
47. Galbis-Reig David. A case report of kratom addiction and withdrawal. WMJ. 2016;115(1):49-52; quiz 53.
48. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciose) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend. 2014;139:132-137.
49. Singh D, Müller CP, Vicknasingam, et al. Social functioning of kratom (Mitragyna speciosa) users in Malaysia. J Psychoactive Drugs. 2015;47(2):125-131.
50. Khazaeli A, Jerry JM, Vazirian M. Treatment of kratom withdrawal and addiction with buprenorphine. J Addict Med. 2018;12(6):493-495.
51. Buresh M. Treatment of kratom dependence with buprenorphine-naloxone maintenance. J Addict Med. 2018;12(6):481-483.
52. Overbeek DL, Abraham J, Munzer BW. Kratom (mitragynine) ingestion requiring naloxone reversal. Clin Pract Cases Emerg Med. 2019;3(1):24-26.
1. Henningfield JE, Fant RV, Wang DW. The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research. Psychopharmacology (Berl). 2018;235(2):573-589.
2. Chang-Chien GC, Odonkor CA, Amorapanth P, et al. Is kratom the new ‘legal high’ on the block?: the case of an emerging opioid receptor agonist with substance abuse potential. Pain Physician. 2017;20(1):E195-E198.
3. Penders T, Jones WB. Kratom, a substance of increasing concern [PCSS webinar]. Providers Clinical Support System. November 28, 2018. https://pcssnow.org/event/kratom-a-substance-of-increasing-concern. Accessed January 29, 2020.
4. Grundmann O. Patterns of kratom use and health impact in the US-results from an online survey. Drug Alcohol Depend. 2017;176:63-70.
5. US Drug Enforcement Administration. Drugs of concern. https://www.dea.gov/sites/default/files/sites/getsmartaboutdrugs.com/files/publications/DoA_2017Ed_Updated_6.16.17.pdf#page=84. Updated June 16, 2017. Accessed January 29, 2020.
6. Matsumoto K, Horie S, Ishikawa H, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sciences. 2004;74(17):2143-2155.
7. Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull (Tokyo). 2004;52(8):916-928.
8. Suhaimi FW, Yusoff NH, Hassan R, et al. Neurobiology of kratom and its main alkaloid mitragynine. Brain Res Bull. 2016;126(pt 1):29-40.
9. Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012;112(12):792-799.
10. Kruegel AC, Uprety R, Grinnell SG, et al. 7-hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. ACS Cent Sci. 2019;5(6):992-1001.
11. Trakulsrichai S, Sathirakul K, Auparakkitanon S, et al. Pharmacokinetics of mitragynine in man. Drug Des Devel Ther. 2015:9:2421-2429.
12. Warner ML, Kaufman NC, Grundmann O, et al. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Intl J Legal Med. 2016;130(1):127-138.
13. Stanciu CN, Gnanasegaram SA, Ahmed S, et al. Kratom withdrawal: a systematic review with case series. J Psychoactive Drugs. 2019;51(1):12-18.
14. Kamble SH, Sharma A, King TI, et al. Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom). Xenobiotica. 2019;49(11):1279-1288.
15. Smith LC, Lin L, Hwang CS, et al. Lateral flow assessment and unanticipated toxicity of kratom. Chem Res Toxicol. 2019;32(1):113-121.
16. Saingam D, Assanangkornchai S, Geater AF, et al. Factor analytical investigation of Krathom (Mitragyna speciosa Korth.) withdrawal syndrome in Thailand. J Psychoactive Drugs. 2016;48(2):76-85.
17. Vicknasingam B, Narayanan S, Beng GT, et al. The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. Int J Drug Policy. 2010;21(4):283-288.
18. Saingam D, Assanangkornchai S, Geater AF, et al. Pattern and consequences of krathom (Mitragyna speciosa Korth.) use among male villagers in southern Thailand: a qualitative study. Int J Drug Policy. 2013;24(4):351-358.
19. Fernandes CT, Iqbal U, Tighe SP, et al. Kratom-induced cholestatic liver injury and its conservative management. J Investig Med High Impact Case Rep. 2019;7:2324709619836138. doi: 10.1177/2324709619836138.
20. Dorman C, Wong M, Khan A. Cholestatic hepatitis from prolonged kratom use: a case report. Hepatology. 2015;61(3):1086-1087.
21. Osborne CS, Overstreet AN, Rockey DC, et al. Drug-induced liver injury caused by kratom use as an alternative pain treatment amid an ongoing opioid epidemic. J Investig Med High Impact Case Rep. 2019;7:2324709619826167. doi: 10.1177/2324709619826167.
22. Mousa MS, Sephien A, Gutierrez J, et al. N-acetylcysteine for acute hepatitis induced by kratom herbal tea. Am J Ther. 2018;25(5):e550-e551.
23. Riverso M, Chang M, Soldevila-Pico C, et al. Histologic characterization of kratom use-associated liver injury. Gastroenterology Res. 2018;11(1):79-82.
24. Kapp FG, Maurer HH, Auwärter V, et al. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol. 2011;7(3):227-231.
25. Antony A, Lee TP. Herb-induced liver injury with cholestasis and renal injury secondary to short-term use of kratom (Mitragyna speciosa). Am J Ther. 2019;26(4):e546-e547.
26. Palasamudram Shekar S, Rojas EE, D’Angelo CC, et al. Legally lethal kratom: a herbal supplement with overdose potential. J Psychoactive Drugs. 2019;51(1):28-30.
27. Aldyab M, Ells PF, Bui R, et al. Kratom-induced cholestatic liver injury mimicking anti-mitochondrial antibody-negative primary biliary cholangitis: a case report and review of literature. Gastroenterology Res. 2019;12(4):211-215.
28. Post S, Spiller HA, Chounthirath T. Kratom exposures reported to United States poison control centers: 2011-2017. Clinical Toxicol (Phila). 2019;57(10):847-854.
29. Eggleston W, Stoppacher R, Suen K, et al. Kratom use and toxicities in the United States. Pharmacotherapy. 2019;39(7):775-777.
30. US Food & Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom , underscoring its potential for abuse. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-scientific-evidence-presence-opioid-compounds. Published February 6, 2019. Accessed January 29, 2020.
31. Gershman K, Timm K, Frank M, et al. Deaths in Colorado attributed to kratom. N Engl J Med. 2019;380(1):97-98.
32. Kronstrand R, Roman M, Thelander G, et al. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend krypton. J Anal Toxicol. 2011;35(4):242-247.
33. Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019;15(1):110-113.
34. Abdullah HMA, Haq I, Lamfers R. Cardiac arrest in a young healthy male patient secondary to kratom ingestion: is this ‘legal high’ substance more dangerous than initially thought? BMJ Case Rep. 2019;12(7):pii: e229778. doi: 10.1136/bcr-2019-229778.
35. Laboratory analysis of kratom products for heavy metals. US FDA. https://www.fda.gov/news-events/public-health-focus/laboratory-analysis-kratom-products-heavy-metals. Updated April 3, 2019. Accessed January 29, 2020.
36. FDA investigated multistate outbreak of salmonella infections linked to products reported to contain kratom. US FDA. https://www.fda.gov/food/outbreaks-foodborne-illness/fda-investigated-multistate-outbreak-salmonella-infections-linked-products-reported-contain-kratom. Updated June 29, 2018. Accessed January 14, 2020.
37. Aggarwal G, Robertson E, McKinlay J, et a., Death from kratom toxicity and the possible role of intralipid. J Intensive Care Soc. 2018;19(1):61-63.
38. Drug Facts. Kratom. Confirm Biosciences. https://www.confirmbiosciences.com/knowledge/drug-facts/kratom/. Accessed January 14, 2020.
39. Grinspoon P. How long does kratom stay in the system? Addiction Resource. https://addictionresource.com/drugs/kratom/how-long-kratom-stay-in-your-system/. Updated December 18, 2019. Accessed January 29, 2020.
40. Kaewklum D, Kaewklum M, Pootrakronchai R, et al. Detection of mitragynine and its metaboilite in urine following ingestion of leaves of Mitragyna speciosa korth. Recent Advances in Doping Analysis (13). Proceedings of the Manfred Donike Workshop, 23rd Cologne Workshop on Dope Analysis. 2005:403-406.
41. Lu S, Tran BN, Nelsen JL, et al. Quantitative analysis of mitragynine in human urine by high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(24):2499-2505.
42. Philipp AA, Wissenbach DK, Zoerntlein SW, et al. Studies on the metabolism of mitragynine, the main alkaloid of the herbal drug kratom, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry. J Mass Spectrom. 2009;44(8):1249-1261.
43. Manda VK, Bharathi A, Ali Z, et al. Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline. Planta Med. 2014;80(7):568-576.
44. Davidson L, Rawat M, Stojanovski S, et al. Natural drugs, not so natural effects: neonatal abstinence syndrome secondary to ‘kratom‘. J Neonatal Perinatal Med. 2019;12(1):109-112.
45. Mackay L, Abrahams R. Novel case of maternal and neonatal kratom dependence and withdrawal. Can Fam Physician. 2018;64(2):121-122.
46. McWhirter L, Morris S. A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence. Eur Addict Res. 2010;16(4):229-231.
47. Galbis-Reig David. A case report of kratom addiction and withdrawal. WMJ. 2016;115(1):49-52; quiz 53.
48. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciose) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend. 2014;139:132-137.
49. Singh D, Müller CP, Vicknasingam, et al. Social functioning of kratom (Mitragyna speciosa) users in Malaysia. J Psychoactive Drugs. 2015;47(2):125-131.
50. Khazaeli A, Jerry JM, Vazirian M. Treatment of kratom withdrawal and addiction with buprenorphine. J Addict Med. 2018;12(6):493-495.
51. Buresh M. Treatment of kratom dependence with buprenorphine-naloxone maintenance. J Addict Med. 2018;12(6):481-483.
52. Overbeek DL, Abraham J, Munzer BW. Kratom (mitragynine) ingestion requiring naloxone reversal. Clin Pract Cases Emerg Med. 2019;3(1):24-26.
Critical care admissions up for pediatric opioid poisonings
ORLANDO – The proportion of children and adolescents admitted to critical care for serious poisonings has increased in recent years, according to authors of a study of more than 750,000 reported opioid exposures.
Critical care units were involved in 10% of pediatric opioid poisoning cases registered in 2015-2018, up from 7% in 2005-2009, reported Megan E. Land, MD, of Emory University, Atlanta, and coinvestigators.
Attempted suicide has represented an increasingly large proportion of pediatric opioid poisonings from 2005 to 2018, according to the researchers, based on retrospective analysis of cases reported to U.S. poison centers.
Mortality related to these pediatric poisonings increased over time, and among children and adolescents admitted to a pediatric ICU, CPR and naloxone use also increased over time, Dr. Land and associates noted.
These said Dr. Land, who presented the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
“I think that this really requires a two-pronged approach,” she explained. “One is that we need to increase mental health resources for kids to address adolescent suicidality, and secondly, we need to decrease access to opioids in the hands of pediatric patients by decreasing prescribing and then also getting those that are unused out of the homes.”
Jeffrey Zimmerman, MD, past president of SCCM, said these findings on pediatric opioid poisonings represent the “iceberg tip” of a much larger societal issue that has impacts well beyond critical care.
“I think acutely, we’re well equipped to deal with the situation in terms of interventions,” Dr. Zimmerman said in an interview. “The bigger issue is dealing with what happens afterward, when the patient leaves the ICU in the hospital.”
When the issue is chronic opioid use among adolescents or children, critical care specialists can help by initiating opioid tapering in the hospital setting, rather than allowing the complete weaning process to play out at home, he said.
All clinicians can help prevent future injury by asking questions of the child and family to ensure that any opiates and other prescription medications at home are locked up, he added.
“These aren’t very glamorous things, but they’re common sense, and there’s more need for this common sense now than there ever has been,” Dr. Zimmerman concluded.
The study by Dr. Land and colleagues included data on primary opioid ingestions registered at 55 poison control centers in the United States. They assessed trends over three time periods: 2005-2009, 2010-2014, and 2015-2018.
They found that children under 19 years of age accounted for 28% of the 753,592 opioid poisonings reported over that time period.
The overall number of reported opioid poisonings among children declined somewhat since about 2010. However, the proportion admitted to a critical care unit increased from 7% in the 2005-2009 period to 10% in the 2015-2018 period, said Dr. Land, who added that the probability of a moderate or major effect increased by 0.55% and 0.11% per year, respectively, over the 14 years studied.
Mortality – 0.21% overall – increased from 0.18% in the earliest era to 0.28% in the most recent era, according to the investigators.
Suicidal intent increased from 14% in the earliest era to 21% in the most recent era, and was linked to near tenfold odds of undergoing a pediatric ICU procedure, Dr. Land and colleagues reported.
Among those children admitted to a pediatric ICU, use of CPR increased from 1% to 3% in the earliest and latest time periods, respectively; likewise, naloxone administration increased from 42% to 51% over those two time periods. By contrast, there was no change in use of mechanical ventilation (12%) or vasopressors (3%) over time, they added.
The opioids most commonly linked to pediatric ICU procedures were fentanyl (odds ratio, 12), heroin (OR, 11), and methadone (OR, 15).
Some funding for the study came from the Georgia Poison Center. Dr. Land had no disclosures relevant to the research.
SOURCE: Land M et al. Crit Care Med. 2020 doi: 10.1097/01.ccm.0000618708.38414.ea.
ORLANDO – The proportion of children and adolescents admitted to critical care for serious poisonings has increased in recent years, according to authors of a study of more than 750,000 reported opioid exposures.
Critical care units were involved in 10% of pediatric opioid poisoning cases registered in 2015-2018, up from 7% in 2005-2009, reported Megan E. Land, MD, of Emory University, Atlanta, and coinvestigators.
Attempted suicide has represented an increasingly large proportion of pediatric opioid poisonings from 2005 to 2018, according to the researchers, based on retrospective analysis of cases reported to U.S. poison centers.
Mortality related to these pediatric poisonings increased over time, and among children and adolescents admitted to a pediatric ICU, CPR and naloxone use also increased over time, Dr. Land and associates noted.
These said Dr. Land, who presented the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
“I think that this really requires a two-pronged approach,” she explained. “One is that we need to increase mental health resources for kids to address adolescent suicidality, and secondly, we need to decrease access to opioids in the hands of pediatric patients by decreasing prescribing and then also getting those that are unused out of the homes.”
Jeffrey Zimmerman, MD, past president of SCCM, said these findings on pediatric opioid poisonings represent the “iceberg tip” of a much larger societal issue that has impacts well beyond critical care.
“I think acutely, we’re well equipped to deal with the situation in terms of interventions,” Dr. Zimmerman said in an interview. “The bigger issue is dealing with what happens afterward, when the patient leaves the ICU in the hospital.”
When the issue is chronic opioid use among adolescents or children, critical care specialists can help by initiating opioid tapering in the hospital setting, rather than allowing the complete weaning process to play out at home, he said.
All clinicians can help prevent future injury by asking questions of the child and family to ensure that any opiates and other prescription medications at home are locked up, he added.
“These aren’t very glamorous things, but they’re common sense, and there’s more need for this common sense now than there ever has been,” Dr. Zimmerman concluded.
The study by Dr. Land and colleagues included data on primary opioid ingestions registered at 55 poison control centers in the United States. They assessed trends over three time periods: 2005-2009, 2010-2014, and 2015-2018.
They found that children under 19 years of age accounted for 28% of the 753,592 opioid poisonings reported over that time period.
The overall number of reported opioid poisonings among children declined somewhat since about 2010. However, the proportion admitted to a critical care unit increased from 7% in the 2005-2009 period to 10% in the 2015-2018 period, said Dr. Land, who added that the probability of a moderate or major effect increased by 0.55% and 0.11% per year, respectively, over the 14 years studied.
Mortality – 0.21% overall – increased from 0.18% in the earliest era to 0.28% in the most recent era, according to the investigators.
Suicidal intent increased from 14% in the earliest era to 21% in the most recent era, and was linked to near tenfold odds of undergoing a pediatric ICU procedure, Dr. Land and colleagues reported.
Among those children admitted to a pediatric ICU, use of CPR increased from 1% to 3% in the earliest and latest time periods, respectively; likewise, naloxone administration increased from 42% to 51% over those two time periods. By contrast, there was no change in use of mechanical ventilation (12%) or vasopressors (3%) over time, they added.
The opioids most commonly linked to pediatric ICU procedures were fentanyl (odds ratio, 12), heroin (OR, 11), and methadone (OR, 15).
Some funding for the study came from the Georgia Poison Center. Dr. Land had no disclosures relevant to the research.
SOURCE: Land M et al. Crit Care Med. 2020 doi: 10.1097/01.ccm.0000618708.38414.ea.
ORLANDO – The proportion of children and adolescents admitted to critical care for serious poisonings has increased in recent years, according to authors of a study of more than 750,000 reported opioid exposures.
Critical care units were involved in 10% of pediatric opioid poisoning cases registered in 2015-2018, up from 7% in 2005-2009, reported Megan E. Land, MD, of Emory University, Atlanta, and coinvestigators.
Attempted suicide has represented an increasingly large proportion of pediatric opioid poisonings from 2005 to 2018, according to the researchers, based on retrospective analysis of cases reported to U.S. poison centers.
Mortality related to these pediatric poisonings increased over time, and among children and adolescents admitted to a pediatric ICU, CPR and naloxone use also increased over time, Dr. Land and associates noted.
These said Dr. Land, who presented the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
“I think that this really requires a two-pronged approach,” she explained. “One is that we need to increase mental health resources for kids to address adolescent suicidality, and secondly, we need to decrease access to opioids in the hands of pediatric patients by decreasing prescribing and then also getting those that are unused out of the homes.”
Jeffrey Zimmerman, MD, past president of SCCM, said these findings on pediatric opioid poisonings represent the “iceberg tip” of a much larger societal issue that has impacts well beyond critical care.
“I think acutely, we’re well equipped to deal with the situation in terms of interventions,” Dr. Zimmerman said in an interview. “The bigger issue is dealing with what happens afterward, when the patient leaves the ICU in the hospital.”
When the issue is chronic opioid use among adolescents or children, critical care specialists can help by initiating opioid tapering in the hospital setting, rather than allowing the complete weaning process to play out at home, he said.
All clinicians can help prevent future injury by asking questions of the child and family to ensure that any opiates and other prescription medications at home are locked up, he added.
“These aren’t very glamorous things, but they’re common sense, and there’s more need for this common sense now than there ever has been,” Dr. Zimmerman concluded.
The study by Dr. Land and colleagues included data on primary opioid ingestions registered at 55 poison control centers in the United States. They assessed trends over three time periods: 2005-2009, 2010-2014, and 2015-2018.
They found that children under 19 years of age accounted for 28% of the 753,592 opioid poisonings reported over that time period.
The overall number of reported opioid poisonings among children declined somewhat since about 2010. However, the proportion admitted to a critical care unit increased from 7% in the 2005-2009 period to 10% in the 2015-2018 period, said Dr. Land, who added that the probability of a moderate or major effect increased by 0.55% and 0.11% per year, respectively, over the 14 years studied.
Mortality – 0.21% overall – increased from 0.18% in the earliest era to 0.28% in the most recent era, according to the investigators.
Suicidal intent increased from 14% in the earliest era to 21% in the most recent era, and was linked to near tenfold odds of undergoing a pediatric ICU procedure, Dr. Land and colleagues reported.
Among those children admitted to a pediatric ICU, use of CPR increased from 1% to 3% in the earliest and latest time periods, respectively; likewise, naloxone administration increased from 42% to 51% over those two time periods. By contrast, there was no change in use of mechanical ventilation (12%) or vasopressors (3%) over time, they added.
The opioids most commonly linked to pediatric ICU procedures were fentanyl (odds ratio, 12), heroin (OR, 11), and methadone (OR, 15).
Some funding for the study came from the Georgia Poison Center. Dr. Land had no disclosures relevant to the research.
SOURCE: Land M et al. Crit Care Med. 2020 doi: 10.1097/01.ccm.0000618708.38414.ea.
REPORTING FROM CCC49
For OUD patients, ‘a lot of work to be done’
Most Americans who need medication-assisted treatment not getting it
LAS VEGAS – For Karen J. Hartwell, MD, few things in her clinical work bring more reward than providing medication-assisted treatment (MAT) to patients with opioid use disorder.
or to see a depression remit on your selection of an antidepressant,” she said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We know that medication-assisted treatment is underused and, sadly, relapse rates remain high.”
According to the Centers for Disease Control and Prevention, there were 70,237 drug-related overdose deaths in 2017 – 47,600 from prescription and illicit opioids. “This is being driven predominately by fentanyl and other high-potency synthetic opioids, followed by prescription opioids and heroin,” said Dr. Hartwell, an associate professor in the addiction sciences division in the department of psychiatry and behavioral sciences at the Medical University of South Carolina, Charleston.
There were an estimated 2 million Americans with an opioid use disorder (OUD) in 2018, she said, and more than 10 million misused prescription opioids. At the same time, prescriptions for opioids have dropped to lowest level in 10 years from a peak in 2012 of 81.3 prescriptions per 100 persons to 58.7 prescriptions per 100 persons in 2017 – total of more than 191 million scripts. “There is a decline in the number of opioid prescriptions, but there is still a lot of diversion, and there are some prescription ‘hot spots’ in the Southeast,” Dr. Hartwell said. “Heroin is a very low cost, and we’re wrestling with the issue of fentanyl.”
To complicate matters, most Americans with opioid use disorder are not in treatment. “In many people, the disorder is never diagnosed, and even fewer engage in care,” she said. “There are challenges with treatment retention, and even fewer achieve remission. There’s a lot of work to be done. One of which is the availability of medication-assisted treatment.”
Dr. Hartwell said that she knows of physician colleagues who have obtained a waiver to prescribe buprenorphine but have yet to prescribe it. “Some people may prefer to avoid the dance [of buprenorphine prescribing],” she said. “I’m here to advise you to dance.” Clinicians can learn about MAT waiver training opportunities by visiting the website of the Providers Clinical Support System, a program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Another option is to join a telementoring session on the topic facilitated by Project ECHO, or Extension for Community Healthcare Outcomes, which is being used by the University of New Mexico, Albuquerque. The goal of this model is to break down the walls between specialty and primary care by linking experts at an academic “hub” with primary care doctors and nurses in nearby communities.
“Our Project ECHO at the Medical University of South Carolina is twice a month on Fridays,” Dr. Hartwell said. “The first half is a case. The second half is a didactic [session], and you get a free hour of CME.”
The most common drugs used for medication-assisted treatment of opioid disorder are buprenorphine (a partial agonist), naltrexone (an antagonist), and methadone (a full agonist). Methadone retention generally is better than buprenorphine or naltrexone. The recommended treatment duration is 6-12 months, yet many studies demonstrate that many only stay on treatment for 30-60 days.
“You want to keep patients on treatment as long as they benefit from the medication,” Dr. Hartwell said. One large study of Medicaid claims data found that the risk of acute care service use and overdose were high following buprenorphine discontinuation, regardless of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high (Am J Psychiatry. 2020 Feb 1;177[2]:117-24). About 5% of patients across all cohorts experienced one or more medically treated overdoses.
“One thing I don’t want is for people to drop out of treatment and not come back to see me,” Dr. Hartwell said. “This is a time for us to use our shared decision-making skills. I like to use the Tapering Readiness Inventory, a list of 16 questions. It asks such things as ‘Are you able to cope with difficult situations without using?’ and ‘Do you have all of the [drug] paraphernalia out of the house?’ We then have a discussion. If the patient decides to go ahead and do a taper, I always leave the door open. So, as that taper persists and someone says, ‘I’m starting to think about using, Doctor,’ I’ll put them back on [buprenorphine]. Or, if they come off the drug and they find themselves at risk of relapsing, they come back in and see me.”
There’s also some evidence that contingency management might be helpful, both in terms of opioid negative urines, and retention and treatment. Meanwhile, extended-release forms of buprenorphine are emerging.
In 2017, the Food and Drug Administration approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe OUD in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. “The recommendations are that you have about a 7-day lead-in of sublingual buprenorphine, and then 2 months of a 300-mg IV injection,” Dr. Hartwell said. “This is followed by either 100-mg injections monthly or 300-mg maintenance in select cases. There is some pain at the injection site. Some clinicians are getting around this by using a little bit of lidocaine prior to giving the injection.”
Another product, Brixadi, is an extended-release weekly (8 mg, 16 mg, 24 mg, 32 mg) and monthly (64 mg, 96 mg, 128 mg) buprenorphine injection used for the treatment of moderate to severe OUD. It is expected to be available in December 2020.
In 2016, the FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of buprenorphine, as part of a complete treatment program. “The 6-month duration kind of takes the issue of adherence off the table,” Dr. Hartwell said. “The caveat with this is that you have to be stable on 8 mg of buprenorphine per day or less. The majority of my patients require much higher doses.”
Dr. Hartwell reported having no relevant disclosures.
Most Americans who need medication-assisted treatment not getting it
Most Americans who need medication-assisted treatment not getting it
LAS VEGAS – For Karen J. Hartwell, MD, few things in her clinical work bring more reward than providing medication-assisted treatment (MAT) to patients with opioid use disorder.
or to see a depression remit on your selection of an antidepressant,” she said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We know that medication-assisted treatment is underused and, sadly, relapse rates remain high.”
According to the Centers for Disease Control and Prevention, there were 70,237 drug-related overdose deaths in 2017 – 47,600 from prescription and illicit opioids. “This is being driven predominately by fentanyl and other high-potency synthetic opioids, followed by prescription opioids and heroin,” said Dr. Hartwell, an associate professor in the addiction sciences division in the department of psychiatry and behavioral sciences at the Medical University of South Carolina, Charleston.
There were an estimated 2 million Americans with an opioid use disorder (OUD) in 2018, she said, and more than 10 million misused prescription opioids. At the same time, prescriptions for opioids have dropped to lowest level in 10 years from a peak in 2012 of 81.3 prescriptions per 100 persons to 58.7 prescriptions per 100 persons in 2017 – total of more than 191 million scripts. “There is a decline in the number of opioid prescriptions, but there is still a lot of diversion, and there are some prescription ‘hot spots’ in the Southeast,” Dr. Hartwell said. “Heroin is a very low cost, and we’re wrestling with the issue of fentanyl.”
To complicate matters, most Americans with opioid use disorder are not in treatment. “In many people, the disorder is never diagnosed, and even fewer engage in care,” she said. “There are challenges with treatment retention, and even fewer achieve remission. There’s a lot of work to be done. One of which is the availability of medication-assisted treatment.”
Dr. Hartwell said that she knows of physician colleagues who have obtained a waiver to prescribe buprenorphine but have yet to prescribe it. “Some people may prefer to avoid the dance [of buprenorphine prescribing],” she said. “I’m here to advise you to dance.” Clinicians can learn about MAT waiver training opportunities by visiting the website of the Providers Clinical Support System, a program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Another option is to join a telementoring session on the topic facilitated by Project ECHO, or Extension for Community Healthcare Outcomes, which is being used by the University of New Mexico, Albuquerque. The goal of this model is to break down the walls between specialty and primary care by linking experts at an academic “hub” with primary care doctors and nurses in nearby communities.
“Our Project ECHO at the Medical University of South Carolina is twice a month on Fridays,” Dr. Hartwell said. “The first half is a case. The second half is a didactic [session], and you get a free hour of CME.”
The most common drugs used for medication-assisted treatment of opioid disorder are buprenorphine (a partial agonist), naltrexone (an antagonist), and methadone (a full agonist). Methadone retention generally is better than buprenorphine or naltrexone. The recommended treatment duration is 6-12 months, yet many studies demonstrate that many only stay on treatment for 30-60 days.
“You want to keep patients on treatment as long as they benefit from the medication,” Dr. Hartwell said. One large study of Medicaid claims data found that the risk of acute care service use and overdose were high following buprenorphine discontinuation, regardless of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high (Am J Psychiatry. 2020 Feb 1;177[2]:117-24). About 5% of patients across all cohorts experienced one or more medically treated overdoses.
“One thing I don’t want is for people to drop out of treatment and not come back to see me,” Dr. Hartwell said. “This is a time for us to use our shared decision-making skills. I like to use the Tapering Readiness Inventory, a list of 16 questions. It asks such things as ‘Are you able to cope with difficult situations without using?’ and ‘Do you have all of the [drug] paraphernalia out of the house?’ We then have a discussion. If the patient decides to go ahead and do a taper, I always leave the door open. So, as that taper persists and someone says, ‘I’m starting to think about using, Doctor,’ I’ll put them back on [buprenorphine]. Or, if they come off the drug and they find themselves at risk of relapsing, they come back in and see me.”
There’s also some evidence that contingency management might be helpful, both in terms of opioid negative urines, and retention and treatment. Meanwhile, extended-release forms of buprenorphine are emerging.
In 2017, the Food and Drug Administration approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe OUD in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. “The recommendations are that you have about a 7-day lead-in of sublingual buprenorphine, and then 2 months of a 300-mg IV injection,” Dr. Hartwell said. “This is followed by either 100-mg injections monthly or 300-mg maintenance in select cases. There is some pain at the injection site. Some clinicians are getting around this by using a little bit of lidocaine prior to giving the injection.”
Another product, Brixadi, is an extended-release weekly (8 mg, 16 mg, 24 mg, 32 mg) and monthly (64 mg, 96 mg, 128 mg) buprenorphine injection used for the treatment of moderate to severe OUD. It is expected to be available in December 2020.
In 2016, the FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of buprenorphine, as part of a complete treatment program. “The 6-month duration kind of takes the issue of adherence off the table,” Dr. Hartwell said. “The caveat with this is that you have to be stable on 8 mg of buprenorphine per day or less. The majority of my patients require much higher doses.”
Dr. Hartwell reported having no relevant disclosures.
LAS VEGAS – For Karen J. Hartwell, MD, few things in her clinical work bring more reward than providing medication-assisted treatment (MAT) to patients with opioid use disorder.
or to see a depression remit on your selection of an antidepressant,” she said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We know that medication-assisted treatment is underused and, sadly, relapse rates remain high.”
According to the Centers for Disease Control and Prevention, there were 70,237 drug-related overdose deaths in 2017 – 47,600 from prescription and illicit opioids. “This is being driven predominately by fentanyl and other high-potency synthetic opioids, followed by prescription opioids and heroin,” said Dr. Hartwell, an associate professor in the addiction sciences division in the department of psychiatry and behavioral sciences at the Medical University of South Carolina, Charleston.
There were an estimated 2 million Americans with an opioid use disorder (OUD) in 2018, she said, and more than 10 million misused prescription opioids. At the same time, prescriptions for opioids have dropped to lowest level in 10 years from a peak in 2012 of 81.3 prescriptions per 100 persons to 58.7 prescriptions per 100 persons in 2017 – total of more than 191 million scripts. “There is a decline in the number of opioid prescriptions, but there is still a lot of diversion, and there are some prescription ‘hot spots’ in the Southeast,” Dr. Hartwell said. “Heroin is a very low cost, and we’re wrestling with the issue of fentanyl.”
To complicate matters, most Americans with opioid use disorder are not in treatment. “In many people, the disorder is never diagnosed, and even fewer engage in care,” she said. “There are challenges with treatment retention, and even fewer achieve remission. There’s a lot of work to be done. One of which is the availability of medication-assisted treatment.”
Dr. Hartwell said that she knows of physician colleagues who have obtained a waiver to prescribe buprenorphine but have yet to prescribe it. “Some people may prefer to avoid the dance [of buprenorphine prescribing],” she said. “I’m here to advise you to dance.” Clinicians can learn about MAT waiver training opportunities by visiting the website of the Providers Clinical Support System, a program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Another option is to join a telementoring session on the topic facilitated by Project ECHO, or Extension for Community Healthcare Outcomes, which is being used by the University of New Mexico, Albuquerque. The goal of this model is to break down the walls between specialty and primary care by linking experts at an academic “hub” with primary care doctors and nurses in nearby communities.
“Our Project ECHO at the Medical University of South Carolina is twice a month on Fridays,” Dr. Hartwell said. “The first half is a case. The second half is a didactic [session], and you get a free hour of CME.”
The most common drugs used for medication-assisted treatment of opioid disorder are buprenorphine (a partial agonist), naltrexone (an antagonist), and methadone (a full agonist). Methadone retention generally is better than buprenorphine or naltrexone. The recommended treatment duration is 6-12 months, yet many studies demonstrate that many only stay on treatment for 30-60 days.
“You want to keep patients on treatment as long as they benefit from the medication,” Dr. Hartwell said. One large study of Medicaid claims data found that the risk of acute care service use and overdose were high following buprenorphine discontinuation, regardless of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high (Am J Psychiatry. 2020 Feb 1;177[2]:117-24). About 5% of patients across all cohorts experienced one or more medically treated overdoses.
“One thing I don’t want is for people to drop out of treatment and not come back to see me,” Dr. Hartwell said. “This is a time for us to use our shared decision-making skills. I like to use the Tapering Readiness Inventory, a list of 16 questions. It asks such things as ‘Are you able to cope with difficult situations without using?’ and ‘Do you have all of the [drug] paraphernalia out of the house?’ We then have a discussion. If the patient decides to go ahead and do a taper, I always leave the door open. So, as that taper persists and someone says, ‘I’m starting to think about using, Doctor,’ I’ll put them back on [buprenorphine]. Or, if they come off the drug and they find themselves at risk of relapsing, they come back in and see me.”
There’s also some evidence that contingency management might be helpful, both in terms of opioid negative urines, and retention and treatment. Meanwhile, extended-release forms of buprenorphine are emerging.
In 2017, the Food and Drug Administration approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe OUD in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. “The recommendations are that you have about a 7-day lead-in of sublingual buprenorphine, and then 2 months of a 300-mg IV injection,” Dr. Hartwell said. “This is followed by either 100-mg injections monthly or 300-mg maintenance in select cases. There is some pain at the injection site. Some clinicians are getting around this by using a little bit of lidocaine prior to giving the injection.”
Another product, Brixadi, is an extended-release weekly (8 mg, 16 mg, 24 mg, 32 mg) and monthly (64 mg, 96 mg, 128 mg) buprenorphine injection used for the treatment of moderate to severe OUD. It is expected to be available in December 2020.
In 2016, the FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of buprenorphine, as part of a complete treatment program. “The 6-month duration kind of takes the issue of adherence off the table,” Dr. Hartwell said. “The caveat with this is that you have to be stable on 8 mg of buprenorphine per day or less. The majority of my patients require much higher doses.”
Dr. Hartwell reported having no relevant disclosures.
REPORTING FROM NPA 2020
U.S. heroin use: Good news, bad news?
U.S. rates of heroin use, heroin use disorder, and heroin injections all increased overall among adults during a recent 17-year period, but rates have plateaued, new research shows.
Although on the face of it this may seem like good news, investigators at the Substance Abuse and Mental Health Services Administration (SAMHSA) note that the plateau in heroin use may simply reflect a switch to fentanyl.
“The recent leveling off of heroin use might reflect shifts from heroin to illicit fentanyl-related compounds,” wrote the investigators, led by Beth Han, MD, PhD, MPH.
The study was published online Feb. 11 as a research letter in JAMA (2020;323[6]:568-71).
National data
For the study, researchers collected data from a nationally representative group of adults aged 18 years or older who participated in the 2002-2018 National Survey on Drug Use and Health (NSDUH).
The analysis included 800,500 respondents during the study period. The mean age of respondents was 34.5 years, and 53.2% were women.
Results showed that the reported past-year prevalence of heroin use increased from 0.17% in 2002 to 0.32% in 2018 (average annual percentage change [AAPC], 5.6; 95% confidence interval [CI], 1.0-10.5; P = .02). During 2002-2016, the APC was 7.6 (95% CI, 6.3-9.0; P less than .001) but then plateaued during 2016-2018 (APC, –7.1; 95% CI, –36.9 to 36.7; P = .69).
The prevalence of heroin use disorder increased from 0.10% in 2002 to 0.21% in 2018 (AAPC, 6.0; 95% CI, 3.2-8.8; P less than .001). The rate remained stable during 2002-2008, increased during 2008-2015, then plateaued during 2015-2018.
The prevalence of heroin injections increased from 0.09% in 2002 to 0.17% in 2018 (AAPC, 6.9; 95% CI, 5.7-8.0; P less than .001), although there was a dip from the previous year. This rate increased during the study period among both men and women, those aged 35-49 years, non-Hispanic whites, and those residing in the Northeast or West regions.
For individuals up to age 25 years and those living in the Midwest, the heroin injection rate stopped increasing and plateaued, but there was an overall increase during the study period.
In 2018, the rate of past-year heroin injection was highest in those in the Northeast, those up to age 49 years, men, and non-Hispanic whites.
More infectious disease testing
Prevalence of heroin injection did not increase among adults who used heroin or who had heroin use disorder. This, the researchers note, “suggests that increases in heroin injection are related to overall increases in heroin use rather than increases in the propensity to inject.”
Future research should examine differences in heroin injection trends across subgroups, the authors wrote.
The researchers advocate for expanding HIV and hepatitis testing and treatment, the provision of sterile syringes, and use of Food and Drug Administration–approved medications for opioid use disorders, particularly among populations at greatest risk – adults in the Northeast, those aged 18-49 years, men, and non-Hispanic whites.
“In parallel, interventions to prevent opioid misuse and opioid use disorder are needed to avert further increases in injection drug use,” they noted.
A limitation of the study was that the NSDUH excludes jail and prison populations and homeless people not in living shelters. In addition, the NSDUH is subject to recall bias.
The study was jointly sponsored by SAMHSA and the National Institute on Drug Abuse of the National Institutes of Health. One author reports owning stock in General Electric Co, 3M Co, and Pfizer Inc.
A version of this article first appeared on Medscape.com.
U.S. rates of heroin use, heroin use disorder, and heroin injections all increased overall among adults during a recent 17-year period, but rates have plateaued, new research shows.
Although on the face of it this may seem like good news, investigators at the Substance Abuse and Mental Health Services Administration (SAMHSA) note that the plateau in heroin use may simply reflect a switch to fentanyl.
“The recent leveling off of heroin use might reflect shifts from heroin to illicit fentanyl-related compounds,” wrote the investigators, led by Beth Han, MD, PhD, MPH.
The study was published online Feb. 11 as a research letter in JAMA (2020;323[6]:568-71).
National data
For the study, researchers collected data from a nationally representative group of adults aged 18 years or older who participated in the 2002-2018 National Survey on Drug Use and Health (NSDUH).
The analysis included 800,500 respondents during the study period. The mean age of respondents was 34.5 years, and 53.2% were women.
Results showed that the reported past-year prevalence of heroin use increased from 0.17% in 2002 to 0.32% in 2018 (average annual percentage change [AAPC], 5.6; 95% confidence interval [CI], 1.0-10.5; P = .02). During 2002-2016, the APC was 7.6 (95% CI, 6.3-9.0; P less than .001) but then plateaued during 2016-2018 (APC, –7.1; 95% CI, –36.9 to 36.7; P = .69).
The prevalence of heroin use disorder increased from 0.10% in 2002 to 0.21% in 2018 (AAPC, 6.0; 95% CI, 3.2-8.8; P less than .001). The rate remained stable during 2002-2008, increased during 2008-2015, then plateaued during 2015-2018.
The prevalence of heroin injections increased from 0.09% in 2002 to 0.17% in 2018 (AAPC, 6.9; 95% CI, 5.7-8.0; P less than .001), although there was a dip from the previous year. This rate increased during the study period among both men and women, those aged 35-49 years, non-Hispanic whites, and those residing in the Northeast or West regions.
For individuals up to age 25 years and those living in the Midwest, the heroin injection rate stopped increasing and plateaued, but there was an overall increase during the study period.
In 2018, the rate of past-year heroin injection was highest in those in the Northeast, those up to age 49 years, men, and non-Hispanic whites.
More infectious disease testing
Prevalence of heroin injection did not increase among adults who used heroin or who had heroin use disorder. This, the researchers note, “suggests that increases in heroin injection are related to overall increases in heroin use rather than increases in the propensity to inject.”
Future research should examine differences in heroin injection trends across subgroups, the authors wrote.
The researchers advocate for expanding HIV and hepatitis testing and treatment, the provision of sterile syringes, and use of Food and Drug Administration–approved medications for opioid use disorders, particularly among populations at greatest risk – adults in the Northeast, those aged 18-49 years, men, and non-Hispanic whites.
“In parallel, interventions to prevent opioid misuse and opioid use disorder are needed to avert further increases in injection drug use,” they noted.
A limitation of the study was that the NSDUH excludes jail and prison populations and homeless people not in living shelters. In addition, the NSDUH is subject to recall bias.
The study was jointly sponsored by SAMHSA and the National Institute on Drug Abuse of the National Institutes of Health. One author reports owning stock in General Electric Co, 3M Co, and Pfizer Inc.
A version of this article first appeared on Medscape.com.
U.S. rates of heroin use, heroin use disorder, and heroin injections all increased overall among adults during a recent 17-year period, but rates have plateaued, new research shows.
Although on the face of it this may seem like good news, investigators at the Substance Abuse and Mental Health Services Administration (SAMHSA) note that the plateau in heroin use may simply reflect a switch to fentanyl.
“The recent leveling off of heroin use might reflect shifts from heroin to illicit fentanyl-related compounds,” wrote the investigators, led by Beth Han, MD, PhD, MPH.
The study was published online Feb. 11 as a research letter in JAMA (2020;323[6]:568-71).
National data
For the study, researchers collected data from a nationally representative group of adults aged 18 years or older who participated in the 2002-2018 National Survey on Drug Use and Health (NSDUH).
The analysis included 800,500 respondents during the study period. The mean age of respondents was 34.5 years, and 53.2% were women.
Results showed that the reported past-year prevalence of heroin use increased from 0.17% in 2002 to 0.32% in 2018 (average annual percentage change [AAPC], 5.6; 95% confidence interval [CI], 1.0-10.5; P = .02). During 2002-2016, the APC was 7.6 (95% CI, 6.3-9.0; P less than .001) but then plateaued during 2016-2018 (APC, –7.1; 95% CI, –36.9 to 36.7; P = .69).
The prevalence of heroin use disorder increased from 0.10% in 2002 to 0.21% in 2018 (AAPC, 6.0; 95% CI, 3.2-8.8; P less than .001). The rate remained stable during 2002-2008, increased during 2008-2015, then plateaued during 2015-2018.
The prevalence of heroin injections increased from 0.09% in 2002 to 0.17% in 2018 (AAPC, 6.9; 95% CI, 5.7-8.0; P less than .001), although there was a dip from the previous year. This rate increased during the study period among both men and women, those aged 35-49 years, non-Hispanic whites, and those residing in the Northeast or West regions.
For individuals up to age 25 years and those living in the Midwest, the heroin injection rate stopped increasing and plateaued, but there was an overall increase during the study period.
In 2018, the rate of past-year heroin injection was highest in those in the Northeast, those up to age 49 years, men, and non-Hispanic whites.
More infectious disease testing
Prevalence of heroin injection did not increase among adults who used heroin or who had heroin use disorder. This, the researchers note, “suggests that increases in heroin injection are related to overall increases in heroin use rather than increases in the propensity to inject.”
Future research should examine differences in heroin injection trends across subgroups, the authors wrote.
The researchers advocate for expanding HIV and hepatitis testing and treatment, the provision of sterile syringes, and use of Food and Drug Administration–approved medications for opioid use disorders, particularly among populations at greatest risk – adults in the Northeast, those aged 18-49 years, men, and non-Hispanic whites.
“In parallel, interventions to prevent opioid misuse and opioid use disorder are needed to avert further increases in injection drug use,” they noted.
A limitation of the study was that the NSDUH excludes jail and prison populations and homeless people not in living shelters. In addition, the NSDUH is subject to recall bias.
The study was jointly sponsored by SAMHSA and the National Institute on Drug Abuse of the National Institutes of Health. One author reports owning stock in General Electric Co, 3M Co, and Pfizer Inc.
A version of this article first appeared on Medscape.com.
Patients remain satisfied despite reduced use of opioids post partum
GRAPEVINE, TEX. – The amount of opioids prescribed post partum may decline over time without affecting levels of pain control satisfaction, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Data from a large center indicate that trends in opioid use significantly declined from 2017 to 2019, but not at the expense of adequate pain control, said Nevert Badreldin, MD, assistant professor of obstetrics and gynecology at Northwestern University in Chicago. Patients consistently reported that they were satisfied with inpatient pain control, while opioid use per inpatient day decreased from about 30 morphine milligram equivalents (MME) to less than 20 MME during that time.
To assess trends in postpartum opioid prescribing, opioid use, and pain control satisfaction, Dr. Badreldin and colleagues evaluated data from a prospective observational study. Their analysis included data from women who used an opioid during postpartum hospitalization between May 2017 and July 2019. The researchers excluded women with NSAID or morphine allergies or recent opioid use, as well as those who received general anesthesia without concurrent neuraxial anesthesia, those who underwent peripartum hysterectomy, and women admitted to the ICU.
The investigators used nonparametric tests of trend to assess the difference over time in the proportion of patients who received an opioid prescription at discharge and in the total MME prescribed post partum.
Of 900 women with inpatient opioid use, 471 agreed to be followed after discharge. In that group, the amount of opioid use per inpatient day significantly declined. In addition, the percentage who received an opioid prescription at discharge significantly declined, as did the total MME prescribed at discharge.
“Both inpatient and outpatient satisfaction with pain control were unchanged,” the researchers reported. “In this population, both the frequency and amount of opioid use in the postpartum period declined from 2017 to 2019, without any change in satisfaction with pain control.”
The study was supported by the Society for Maternal-Fetal Medicine/AMAG 2017 Health Policy Award, and a coauthor received support from the National Institute of Child Health and Human Development.
Source: Badreldin N et al. Am J Obstet Gynecol. 2020 Jan;222(1):S93, Abstract 120.
GRAPEVINE, TEX. – The amount of opioids prescribed post partum may decline over time without affecting levels of pain control satisfaction, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Data from a large center indicate that trends in opioid use significantly declined from 2017 to 2019, but not at the expense of adequate pain control, said Nevert Badreldin, MD, assistant professor of obstetrics and gynecology at Northwestern University in Chicago. Patients consistently reported that they were satisfied with inpatient pain control, while opioid use per inpatient day decreased from about 30 morphine milligram equivalents (MME) to less than 20 MME during that time.
To assess trends in postpartum opioid prescribing, opioid use, and pain control satisfaction, Dr. Badreldin and colleagues evaluated data from a prospective observational study. Their analysis included data from women who used an opioid during postpartum hospitalization between May 2017 and July 2019. The researchers excluded women with NSAID or morphine allergies or recent opioid use, as well as those who received general anesthesia without concurrent neuraxial anesthesia, those who underwent peripartum hysterectomy, and women admitted to the ICU.
The investigators used nonparametric tests of trend to assess the difference over time in the proportion of patients who received an opioid prescription at discharge and in the total MME prescribed post partum.
Of 900 women with inpatient opioid use, 471 agreed to be followed after discharge. In that group, the amount of opioid use per inpatient day significantly declined. In addition, the percentage who received an opioid prescription at discharge significantly declined, as did the total MME prescribed at discharge.
“Both inpatient and outpatient satisfaction with pain control were unchanged,” the researchers reported. “In this population, both the frequency and amount of opioid use in the postpartum period declined from 2017 to 2019, without any change in satisfaction with pain control.”
The study was supported by the Society for Maternal-Fetal Medicine/AMAG 2017 Health Policy Award, and a coauthor received support from the National Institute of Child Health and Human Development.
Source: Badreldin N et al. Am J Obstet Gynecol. 2020 Jan;222(1):S93, Abstract 120.
GRAPEVINE, TEX. – The amount of opioids prescribed post partum may decline over time without affecting levels of pain control satisfaction, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Data from a large center indicate that trends in opioid use significantly declined from 2017 to 2019, but not at the expense of adequate pain control, said Nevert Badreldin, MD, assistant professor of obstetrics and gynecology at Northwestern University in Chicago. Patients consistently reported that they were satisfied with inpatient pain control, while opioid use per inpatient day decreased from about 30 morphine milligram equivalents (MME) to less than 20 MME during that time.
To assess trends in postpartum opioid prescribing, opioid use, and pain control satisfaction, Dr. Badreldin and colleagues evaluated data from a prospective observational study. Their analysis included data from women who used an opioid during postpartum hospitalization between May 2017 and July 2019. The researchers excluded women with NSAID or morphine allergies or recent opioid use, as well as those who received general anesthesia without concurrent neuraxial anesthesia, those who underwent peripartum hysterectomy, and women admitted to the ICU.
The investigators used nonparametric tests of trend to assess the difference over time in the proportion of patients who received an opioid prescription at discharge and in the total MME prescribed post partum.
Of 900 women with inpatient opioid use, 471 agreed to be followed after discharge. In that group, the amount of opioid use per inpatient day significantly declined. In addition, the percentage who received an opioid prescription at discharge significantly declined, as did the total MME prescribed at discharge.
“Both inpatient and outpatient satisfaction with pain control were unchanged,” the researchers reported. “In this population, both the frequency and amount of opioid use in the postpartum period declined from 2017 to 2019, without any change in satisfaction with pain control.”
The study was supported by the Society for Maternal-Fetal Medicine/AMAG 2017 Health Policy Award, and a coauthor received support from the National Institute of Child Health and Human Development.
Source: Badreldin N et al. Am J Obstet Gynecol. 2020 Jan;222(1):S93, Abstract 120.
REPORTING FROM THE PREGNANCY MEETING
Opioid use disorder in adolescents: An overview
Ms. L, age 17, seeks treatment because she has an ongoing struggle with multiple substances, including benzodiazepines, heroin, alcohol, cannabis, and prescription opioids.
She reports that she was 13 when she first used a prescription opioid that was not prescribed for her. She also reports engaging in unsafe sexual practices while using these substances, and has been diagnosed and treated for a sexually transmitted disease. She dropped out of school and is estranged from her family. She says that for a long time she has felt depressed and that she uses drugs to “self-medicate my emotions.” She endorses high anxiety and lack of motivation. Ms. L also reports having several criminal charges for theft, assault, and exchanging sex for drugs. She has undergone 3 admissions for detoxification, but promptly resumed using drugs, primarily heroin and oxycodone, immediately after discharge. Ms. L meets DSM-5 criteria for opioid use disorder (OUD).
Ms. L’s case illustrates a disturbing trend in the current opioid epidemic in the United States. Nearly 11.8 million individuals age ≥12 reported misuse of opioids in the last year.1 Adolescents who misuse prescription or illicit opioids are more likely to be involved with the legal system due to truancy, running away from home, physical altercations, prostitution, exchanging sex for drugs, robbery, and gang involvement. Adolescents who use opioids may also struggle with academic decline, drop out of school early, be unable to maintain a job, and have relationship difficulties, especially with family members.
In this article, I describe the scope of OUD among adolescents, including epidemiology, clinical manifestations, screening tools, and treatment approaches.
Scope of the problem
According to the most recent Monitoring the Future survey of more than 42,500 8th, 10th, and 12th grade students, 2.7% of 12th graders reported prescription opioid misuse (reported in the survey as “narcotics other than heroin”) in the past year.2 In addition, 0.4% of 12th graders reported heroin use over the same period.2 Although the prevalence of opioid use among adolescents has been declining over the past 5 years,2 it still represents a serious health crisis.
Part of the issue may relate to easier access to more potent opioids. For example, heroin available today can be >4 times purer than it was in the past. In 2002, t
Between 1997 and 2012, the annual incidence of youth (age 15 to 19) hospitalizations for prescription opioid poisoning increased >170%.5 Approximately 6% to 9% of youth involved in risky opioid use develop OUD 6 to 12 months after s
Continue to: In recent years...
In recent years, deaths from drug overdose have increased for all age groups; however, limited data is available regarding adolescent overdose deaths. According to the Centers for Disease Control and Prevention (CDC), from 2015 to 2016, drug overdose death rates for persons age 15 to 24 increased to 28%.9
How opioids work
Opioids activate specific transmembrane neurotransmitter receptors, including mu, kappa, and delta, in the CNS and peripheral nervous system (PNS). This leads to activation of G protein–mediated intracellular signal transduction. Mainly it is activation of endogenous mu opioid receptors that mediates the reward, withdrawal, and analgesic effects of opioids. These effects depend on the location of mu receptors. In the CNS, activation of mu opioid receptors may cause miosis, respiratory depression, euphoria, and analgesia.10
Different opioids vary in terms of their half-life; for most opioids, the half-life ranges from 2 to 4 hours.10 Heroin has a half-life of 30 minutes, but due to active metabolites its duration of action is 4 to 5 hours. Opioid metabolites can be detected in urine toxicology within approximately 1 to 2 days since last use.10
Chronic opioid use is associated with neurologic effects that change the function of areas of the brain that control pleasure/reward, stress, decision-making, and more. This leads to cravings, continued substance use, and dependence.11 After continued long-term use, patients report decreased euphoria, but typically they continue to use opioids to avoid withdrawal symptoms or worsening mood.
Criteria for opioid use disorder
In DSM-5, substance use disorders (SUDs)are no longer categorized as abuse or dependence.12 For opioids, the diagnosis is OUD. The Table12 outlines the DSM-5 criteria for OUD. Craving opioids is included for the first time in the OUD diagnosis. Having problems with the legal system is no longer considered a diagnostic criterion for OUD.
Continue to: A vulnerable population
A vulnerable population
As defined by Erik Erikson’s psychosocial stages of development, adolescents struggle between establishing their own identity vs role confusion.13 In an attempt to relate to peers or give in to peer pressure, some adolescents start by experimenting with nicotine, alcohol, and/or marijuana; however, some may move on to using other illicit drugs.14 Risk factors for the development of SUDs include early onset of substance use and a rapid progression through stages of substance use from experimentation to regular use, risky use, and dependence.15 In our case study, Ms. L’s substance use followed a similar pattern. Further, the comorbidity of SUDs and other psychiatric disorders may add a layer of complexity when caring for adolescents. Box 116-20 describes the relationship between comorbid psychiatric disorders and SUDs in adolescents.
Box 1
Disruptive behavior disorders are the most common coexisting psychiatric disorders in an adolescent with a substance use disorder (SUD), including opioid use disorder. These individuals typically present with aggression and other conduct disorder symptoms, and have early involvement with the legal system. Conversely, patients with conduct disorder are at high risk of early initiation of illicit substance use, including opioids. Early onset of substance use is a strong risk factor for developing an SUD.16
Mood disorders, particularly depression, can either precede or occur as a result of heavy and prolonged substance use.17 The estimated prevalence of major depressive disorder in individuals with an SUD is 24% to 50%. Among adolescents, an SUD is also a risk factor for suicidal ideation, suicide attempts, and completed suicide.18-20
Anxiety disorders, especially social phobia, and posttraumatic stress disorder are common in individuals with SUD.
Adolescents with SUD should be carefully evaluated for comorbid psychiatric disorders and treated accordingly.
Clinical manifestations
Common clinical manifestations of opioid use vary depending on when the patient is seen. An individual with OUD may appear acutely intoxicated, be in withdrawal, or show no effects. Chronic/prolonged use can lead to tolerance, such that a user needs to ingest larger amounts of the opioid to produce the same effects.
Acute intoxication can cause sedation, slurring of speech, and pinpoint pupils. Fresh injection sites may be visible on physical examination of IV users. The effects of acute intoxication usually depend on the half-life of the specific opioid and the individual’s tolerance.10 Tolerance to heroin can occur in 10 days and withdrawal can manifest in 3 to 7 hours after last use, depending on dose and purity.3 Tolerance can lead to unintentional overdose and death.
Withdrawal. Individuals experiencing withdrawal from opioids present with flu-like physical symptoms, including generalized body ache, rhinorrhea, diarrhea, goose bumps, lacrimation, and vomiting. Individuals also may experience irritability, restlessness, insomnia, anxiety, and depression during withdrawal.
Other manifestations. Excessive and chronic/prolonged opioid use can adversely impact socio-occupational functioning and cause academic decline in adolescents and youth. Personal relationships are significantly affected. Opioid users may have legal difficulties as a result of committing crimes such as theft, prostitution, or robbery in order to obtain opioids.
Continue to: Screening for OUD
Screening for OUD
Several screening tools are available to assess adolescents for SUDs, including OUD.
CRAFFT is a 6-item, clinician-administered screening tool that has been approved by American Academy of Pediatrics’ Committee on Substance Abuse for adolescents and young adults age <21.21-23 This commonly used tool can assess for alcohol, cannabis, and other drug use. A score ≥2 is considered positive for drug use, indicating that the individual would require further evaluation and assessment22,23 (Figure). There is also a self-administered CRAFFT questionnaire that can be completed by the patient.
NIDA-modified ASSIST. The American Psychiatric Association has adapted the National Institute on Drug Abuse (NIDA)-modified ASSIST. One version is designated for parents/guardians to administer to their children (age 6 to 17), and one is designated for adolescents (age 11 to 17) to self-administer.24,25 Each screening tool has 2 levels: Level 1 screens for substance use and other mental health symptoms, and Level 2 is more specific for substance use alone.
Drug Use Screening Inventory (DUSI) is a self-report questionnaire that has 149 items that assess the use of numerous drugs. It is designed to quantify the severity of consequences associated with drug and alcohol use.26,27
Problem-Oriented Screening Instrument for Teenagers (PO
Continue to: Personal Experience Screening Questionnaire (PESQ)...
Personal Experience Screening Questionnaire (PESQ) is a brief, 40-item, cost-effective, self-report questionnaire that can help identify adolescents (age 12 to 18) who should be referred for further evaluation.30
Addressing treatment expectations
For an adolescent with OUD, treatment should begin in the least restrictive environment that is perceived as safe for the patient. An adolescent’s readiness and motivation to achieve and maintain abstinence are crucial. Treatment planning should include the adolescent as well as his/her family to ensure they are able to verbalize their expectations. Start with a definitive treatment plan that addresses an individual’s needs. The plan should provide structure and an understanding of treatment expectations. The treatment team should clarify the realistic plan and goals based on empirical and clinical evidence. Treatment goals should include interventions to strengthen interpersonal relationships and assist with rehabilitation, such as establishing academic and/or vocational goals. Addressing readiness and working on a patient’s motivation is extremely important for most of these interventions.
In order for any intervention to be successful, clinicians need to establish and foster rapport with the adolescent. By law, substance use or behaviors related to substance use are not allowed to be shared outside the patient-clinician relationship, unless the adolescent gives consent or there are concerns that such behaviors might put the patient or others at risk. It is important to prime the adolescent and help them understand that any information pertaining to their safety or the safety of others may need to be shared outside the patient-clinician relationship.
Choosing an intervention
Less than 50% of a nationally representative sample of 345 addiction treatment programs serving adolescents and adults offer medications for treating OUD.31 Even in programs that offer pharmacotherapy, medications are significantly underutilized. Fewer than 30% of patients in addiction treatment programs receive medication, compared with 74% of patients receiving treatment for other mental health disorders.31 A
Psychotherapy may be used to treat OUD in adolescents. Several family therapies have been studied and are considered as critical psychotherapeutic interventions for treating SUDs, including structural family treatment and functional family therapy approaches.34 An integrated behavioral and family therapy model is also recommended for adolescent patients with SUDs. Cognitive distortions and use of self-deprecatory statements are common among adolescents.35 Therefore, using approaches of cognitive-behavioral therapy (CBT), or CBT plus motivational enhancement therapy, also might be effective for this population.36 The adolescent community reinforcement approach (A-CRA) is a behavioral treatment designed to help adolescents and their families learn how to lead a healthy and happy life without the use of drugs or alcohol by increasing access to social, familial, and educational/vocational reinforcers. Support groups and peer and family support should be encouraged as adjuncts to other interventions. In some areas, sober housing options for adolescents are also available.
Continue to: Harm-reduction strategies
Harm-reduction strategies. Although the primary goal of treatment for adolescents with OUD is to achieve and maintain abstinence from opioid use, implicit and explicit goals can be set. Short-term implicit goals may include harm-reduction strategies that emphasize decreasing the duration, frequency, and amount of substance use and limiting the chances of adverse effects, while the long-term explicit goal should be abstinence from opioid use.
Naloxone nasal spray is used as a harm-reduction strategy. It is an FDA-approved formulation that can reverse the effects of unintentional opioid overdoses and potentially prevent death from respiratory depression.37 Other harm-reduction strategies include needle exchange programs, which provide sterile needles to individuals who inject drugs in an effort to prevent or reduce the transmission of human immunodeficiency virus and other bloodborne viruses that can be spread via shared injection equipment. Fentanyl testing strips allow opioid users to test for the presence fentanyl and fentanyl analogs in the unregulated “street” opioid supply.
Pharmacologic interventions. Because there is limited empirical evidence on the efficacy of medication-assisted treatment (MAT) for adolescents with OUD, clinicians need to rely on evidence from research and experience with adults. Unfortunately, MAT is offered to adolescents considerably less often than it is to adults. Feder et al38 reported that only 2.4% of adolescents received MAT for heroin use and only 0.4% of adolescents received MAT for prescription opioid use, compared with 26.3% and 12% of adults, respectively.
Detoxification. Medications available for detoxification from opioids include opiates (such as methadone or buprenorphine) and clonidine (a central sympathomimetic). If the patient has used heroin for a short period (<1 year) and has no history of detoxification, consider a detoxification strategy with a longer-term taper (90 to 180 days) to allow for stabilization.
Maintenance treatment. Consider maintenance treatment for adolescents with a history of long-term opioid use and at least 2 prior short-term detoxification attempts or nonpharmacotherapy-based treatment within 12 months. Be sure to receive consent from a legal guardian and the patient. Maintenance treatment is usually recommended to continue for 1 to 6 years. Maintenance programs with longer durations have shown higher rates of abstinence, improved engagement, and retention in treatment.39
Continue to: According to guidelines from...
According to guidelines from the American Society of Addiction Medicine (ASAM), adolescents age >16 should be offered MAT; the first-line treatment is buprenorphine.40 To avoid risks of abuse and diversion, a combination of buprenorphine/naloxone may be administered.
Maintenance with buprenorphine
In order to prescribe and dispense buprenorphine, clinicians need to obtain a waiver from the Substance Abuse and Mental Health Services Administration. Before initiating buprenorphine, consider the type of opioid the individual used (short- or long-acting), the severity of the OUD, and the last reported use. The 3 phases of buprenorphine treatment are41:
- Induction phase. Buprenorphine can be initiated at 2 to 4 mg/d. Some patients may require up to 8 mg/d on the first day, which can be administered in divided doses.42 Evaluate and monitor patients carefully during the first few hours after the first dose. Patients should be in early withdrawal; otherwise, the buprenorphine might precipitate withdrawal. The induction phase can be completed in 2 to 4 days by titrating the dose so that the signs and symptoms of opioid withdrawal are minimal, and the patient is able to continue treatment. It may be helpful to have the patient’s legal guardian nearby in case the patient does not tolerate the medication or experiences withdrawal. The initial target dose for buprenorphine is approximately 12 to 16 mg/d.
- Stabilization phase. Patients no longer experience withdrawal symptoms and no longer have cravings. This phase can last 6 to 8 weeks. During this phase, patients should be seen weekly and doses should be adjusted if necessary. As a partial mu agonist, buprenorphine does not activate mu receptors fully and reaches a ceiling effect. Hence, doses >24 mg/d have limited added agonist properties.
- Maintenance phase. Because discontinuation of buprenorphine is associated with high relapse rates, patients may need to be maintained long-term on their stabilization dose, and for some patients, the length of time could be indefinite.39 During this phase, patients continue to undergo follow-up, but do so less frequently.
Methadone maintenance is generally not recommended for individuals age <18.
Preventing opioid diversion
Prescription medications that are kept in the home are a substantial source of opioids for adolescents. In 2014, 56% of 12th graders who did not need medications for medical purposes were able to acquire them from their friends or relatives; 36% of 12th graders used their own prescriptions.21 Limiting adolescents’ access to prescription opioids is the first line of prevention. Box 2 describes interventions and strategies to limit adolescents’ access to opioids.
Box 2
Many adolescents obtain opioids for recreational use from medications that were legitimately prescribed to family or friends. Both clinicians and parents/ guardians can take steps to reduce or prevent this type of diversion
Health care facilities. Regulating the number of pills dispensed to patients is crucial. It is highly recommended to prescribe only the minimal number of opioids necessary. In most cases, 3 to 7 days’ worth of opioids at a time might be sufficient, especially after surgical procedures.
Home. Families can limit adolescents’ access to prescription opioids in the home by keeping all medications in a lock box.
Proper disposal. Various entities offer locations for patients to drop off their unused opioids and other medications for safe disposal. These include police or fire departments and retail pharmacies. The US Drug Enforcement Administration sponsors a National Prescription Drug Take Back Day; see https://www.deadiversion.usdoj.gov/drug_disposal/takeback/index.html. The FDA also offers information on where and how to dispose of unused medicines at https://www.fda.gov/consumers/consumer-updates/where-and-how-dispose-unused-medicines.
CASE CONTINUED
Ms. L is initially prescribed, clonidine, 0.1 mg every 6 hours, to address opioid withdrawal. Clonidine is then tapered and maintained at 0.1 mg twice a day for irritability and impulse control. She is also prescribed sertraline, 100 mg/d, for depression and anxiety, and trazodone, 75 mg as needed at night, to assist with sleep.
Continue to: Following inpatient hospitalization...
Following inpatient hospitalization, during 12 weeks of partial hospital treatment, Ms. L participates in individual psychotherapy sessions 5 days/week; family therapy sessions once a week; and experiential therapy along with group sessions with other peers. She undergoes medication evaluations and adjustments on a weekly basis. Ms. L is now working at a store and is pursuing a high school equivalency certificate. She manages to avoid high-risk behaviors, although she reports having occasional cravings. Ms. L is actively involved in Narcotics Anonymous and has a sponsor. She has reconciled with her mother and moved back home, so she can stay away from her former acquaintances who are still using.
Bottom Line
Adolescents with opioid use disorder can benefit from an individualized treatment plan that includes psychosocial interventions, pharmacotherapy, or a combination of the two. Treatment planning should include the adolescent and his/her family to ensure they are able to verbalize their expectations. Treatment should focus on interventions that strengthen interpersonal relationships and assist with rehabilitation. Ongoing follow-up care is necessary for maintaining abstinence.
Related Resource
- Patkar AA, Weisler RH. Opioid abuse and overdose: Keep your patients safe. Current Psychiatry. 2017;16(8):8-12,14-16.
Drug Brand Names
Buprenorphine • Subutex, Sublocade
Buprenorphine/naloxone • Suboxone
Clonidine • Clorpres
Methadone • Methadose
Naloxone • Narcan
Oxycodone • OxyContin
Sertraline • Zoloft
Tramadol • Ultram
Trazodone • Desyrel, Oleptro
1. Davis JP, Prindle JJ, Eddie D, et al. Addressing the opioid epidemic with behavioral interventions for adolescents and young adults: a quasi-experimental design. J Consult Clin Psychol. 2019;87(10):941-951.
2. National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services. Monitoring the Future Survey: High School and Youth Trends. https://www.drugabuse.gov/publications/drugfacts/monitoring-future-survey-high-school-youth-trends. Updated December 2019. Accessed January 13, 2020.
3. Hopfer CJ, Khuri E, Crowley TJ. Treating adolescent heroin use. J Am Acad Child Adolesc Psychiatry. 2003;42(5):609-611.
4. US Department of Justice, Drug Enforcement Agency, Diversion Control Division. https://www.deadiversion.usdoj.gov/. Accessed January 21, 2020.
5. Gaither JR, Leventhal JM, Ryan SA, et al. National trends in hospitalizations for opioid poisonings among children and adolescents, 1997-2012. JAMA Pediatr. 2016;170(12):1195-1201.
6. Parker MA, Anthony JC. Epidemiological evidence on extra-medical use of prescription pain relievers: transitions from newly incident use to dependence among 12-21 year olds in United States using meta-analysis, 2002-13. Peer J. 2015;3:e1340. doi: 10.7717/peerj.1340. eCollection 2015.
7. Subramaniam GA, Fishman MJ, Woody G. Treatment of opioid-dependent adolescents and young adults with buprenorphine. Curr Psychiatry Rep. 2009;11(5):360-363.
8. Borodovsky JT, Levy S, Fishman M. Buprenorphine treatment for adolescents and young adults with opioid use disorders: a narrative review. J Addict Med. 2018;12(3):170-183.
9. Centers for Disease Control and Prevention: National Center for Health Statistics. Drug overdose deaths in the United States, 1999-2016. https://www.cdc.gov/nchs/products/databriefs/db294.htm. Published December 2017. Accessed January 15, 2020.
10. Strain E. Opioid use disorder: epidemiology, pharmacology, clinical manifestation, course, screening, assessment, diagnosis. https://www.uptodate.com/contents/opioid-use-disorder-epidemiology-pharmacology-clinical-manifestations-course-screening-assessment-and-diagnosis. Updated August 15, 2019. Accessed January 21, 2020.
11. American Academy of Pediatrics Committee on Substance Use and Prevention. Policy statement: medication-assisted treatment of adolescents with opioid use disorder. Pediatrics. 2016;138(3):e20161893. doi: https://doi.org/10.1542/peds.2016-1893.
12. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013:514.
13. Sadock BJ, Sadock VA. Chapter 6: Theories of personality and psychopathology. In: Sadock BJ, Sadock VA, eds. Kaplan and Sadock’s synopsis of psychiatry: behavioral sciences/clinical. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:209.
14. Kandel DB. Stages and pathways of drug involvement: examining the gateway hypothesis. Cambridge, United Kingdom: Cambridge University Press; 2002.
15. Robins LN, McEvoy L. Conduct problems as predictors of substance abuse. In: Robins LN, Rutter M, eds. Straight and devious pathways from childhood to adulthood. Cambridge, United Kingdom: Cambridge University Press; 1990;182-204.
16. Hopfer C, Salomonsen-Sautel S, Mikulich-Gilbertson S, et al. Conduct disorder and initiation of substance use: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2013;52(5):511-518.e4.
17. Armstrong TD, Costello EJ. Community studies on adolescent substance use, abuse, or dependence and psychiatric comorbidity. J Consult Clin Psychol. 2002;70(6):1224-1239.
18. Crumley FE. Substance abuse and adolescent suicidal behavior. JAMA. 1990;263(22):3051-3056.
19. Lewinsohn PM, Rohde P, Seeley JR. Adolescent suicidal ideation and attempts: prevalence, risk factors, and clinical implications. Clinical Psychology: Science and Practice. 1996;3(1):25-46.
20. Kendler KS, Bulik CM, Silberg J, et al. Childhood sexual abuse and adult psychiatric and substance use disorder in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry. 2000;57(10):953-959.
21. Yule AM, Wilens TE, Rausch PK. The opioid epidemic: what a child psychiatrist is to do? J Am Acad Child Adolesc Psychiatry. 2017;56(7);541-543.
22. CRAFFT. https://crafft.org. Accessed January 21, 2020.
23. Knight JR, Sherritt L, Harris SK, et al. Validity of brief alcohol screening tests among adolescents: a comparison of the AUDIT, POSIT, CAGE, and CRAFFT. Alcohol Clin Exp Res. 2003;27(1):67-73.
24. American Psychiatric Association. Online assessment measures. https://www.psychiatry.org/psychiatrists/practice/dsm/educational-resources/assessment-measures. Accessed January 15, 2020.
25. National Institute of Drug Abuse. American Psychiatric Association adapted NIDA modified ASSIST tools. https://www.drugabuse.gov/nidamed-medical-health-professionals/tool-resources-your-practice/screening-assessment-drug-testing-resources/american-psychiatric-association-adapted-nida. Updated November 15, 2015. Accessed January 21, 2020.
26. Canada’s Mental Health & Addiction Network. Drug Use Screening Inventory (DUSI). https://www.porticonetwork.ca/web/knowledgex-archive/amh-specialists/screening-for-cd-in-youth/screening-both-mh-sud/dusi. Published 2009. Accessed January 21, 2020.
27. Tarter RE. Evaluation and treatment of adolescent substance abuse: a decision tree method. Am J Drug Alcohol Abuse. 1990;16(1-2):1-46.
28. Klitzner M, Gruenwald PJ, Taff GA, et al. The adolescent assessment referral system-final report. National Institute on Drug Abuse; Rockville, MD: 1993. NIDA Contract No. 271-89-8252.
29. Slesnick N, Tonigan JS. Assessment of alcohol and other drug use by runaway youths: a test-retest study of the Form 90. Alcohol Treat Q. 2004;22(2):21-34.
30. Winters KC, Kaminer Y. Screening and assessing adolescent substance use disorders in clinical populations. J Am Acad Child Adolesc Psychiatry. 2008;47(7):740-744.
31. Knudsen HK, Abraham AJ, Roman PM. Adoption and implementation of medications in addiction treatment programs. J Addict Med. 2011;5(1):21-27.
32. Deas D, Thomas SE. An overview of controlled study of adolescent substance abuse treatment. Am J Addiction. 2001;10(2):178-189.
33. William RJ, Chang, SY. A comprehensive and comparative review of adolescent substance abuse treatment outcome. Clinical Psychology: Science and Practice. 2000;7(2):138-166.
34. Bukstein OG, Work Group on Quality Issues. Practice parameters for the assessment and treatment of children and adolescents with substance use disorders. J Am Acad Child Adolesc Psychiatry. 2005;44(6):609-621.
35. Van Hasselt VB, Null JA, Kempton T, et al. Social skills and depression in adolescent substance abusers. Addict Behav. 1993;18(1):9-18.
36. Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) study: main findings from two randomized trials. J Subst Abuse Treat. 2004;27(3):197-213.
37. US Food and Drug Administration. Information about naloxone. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-naloxone. Updated December 19, 2019. Accessed January 21, 2020.
38. Feder KA, Krawcyzk N, Saloner, B. Medication-assisted treatment for adolescents in specialty treatment for opioid use disorder. J Adolesc Health. 2018;60(6):747-750.
39. Woody GE, Poole SA, Subramaniam G, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA. 2008;300(17):2003-2011.
40. US Department of Health and Human Services. Substance Abuse and Mental Health Ser-vices Administration. Medication-assisted treatment for opioid addiction in opioid treatment programs: a treatment improvement protocol TIP 43. https://www.asam.org/docs/advocacy/samhsa_tip43_matforopioidaddiction.pdf?sfvrsn=0. Published 2005. Accessed January 15, 2020.
41. US Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment (MAT). https://www.samhsa.gov/medication-assisted-treatment. Updated September 9, 2019. Accessed January 21, 2020.
42. Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend. 2003;70(suppl 2):S59-S77.
Ms. L, age 17, seeks treatment because she has an ongoing struggle with multiple substances, including benzodiazepines, heroin, alcohol, cannabis, and prescription opioids.
She reports that she was 13 when she first used a prescription opioid that was not prescribed for her. She also reports engaging in unsafe sexual practices while using these substances, and has been diagnosed and treated for a sexually transmitted disease. She dropped out of school and is estranged from her family. She says that for a long time she has felt depressed and that she uses drugs to “self-medicate my emotions.” She endorses high anxiety and lack of motivation. Ms. L also reports having several criminal charges for theft, assault, and exchanging sex for drugs. She has undergone 3 admissions for detoxification, but promptly resumed using drugs, primarily heroin and oxycodone, immediately after discharge. Ms. L meets DSM-5 criteria for opioid use disorder (OUD).
Ms. L’s case illustrates a disturbing trend in the current opioid epidemic in the United States. Nearly 11.8 million individuals age ≥12 reported misuse of opioids in the last year.1 Adolescents who misuse prescription or illicit opioids are more likely to be involved with the legal system due to truancy, running away from home, physical altercations, prostitution, exchanging sex for drugs, robbery, and gang involvement. Adolescents who use opioids may also struggle with academic decline, drop out of school early, be unable to maintain a job, and have relationship difficulties, especially with family members.
In this article, I describe the scope of OUD among adolescents, including epidemiology, clinical manifestations, screening tools, and treatment approaches.
Scope of the problem
According to the most recent Monitoring the Future survey of more than 42,500 8th, 10th, and 12th grade students, 2.7% of 12th graders reported prescription opioid misuse (reported in the survey as “narcotics other than heroin”) in the past year.2 In addition, 0.4% of 12th graders reported heroin use over the same period.2 Although the prevalence of opioid use among adolescents has been declining over the past 5 years,2 it still represents a serious health crisis.
Part of the issue may relate to easier access to more potent opioids. For example, heroin available today can be >4 times purer than it was in the past. In 2002, t
Between 1997 and 2012, the annual incidence of youth (age 15 to 19) hospitalizations for prescription opioid poisoning increased >170%.5 Approximately 6% to 9% of youth involved in risky opioid use develop OUD 6 to 12 months after s
Continue to: In recent years...
In recent years, deaths from drug overdose have increased for all age groups; however, limited data is available regarding adolescent overdose deaths. According to the Centers for Disease Control and Prevention (CDC), from 2015 to 2016, drug overdose death rates for persons age 15 to 24 increased to 28%.9
How opioids work
Opioids activate specific transmembrane neurotransmitter receptors, including mu, kappa, and delta, in the CNS and peripheral nervous system (PNS). This leads to activation of G protein–mediated intracellular signal transduction. Mainly it is activation of endogenous mu opioid receptors that mediates the reward, withdrawal, and analgesic effects of opioids. These effects depend on the location of mu receptors. In the CNS, activation of mu opioid receptors may cause miosis, respiratory depression, euphoria, and analgesia.10
Different opioids vary in terms of their half-life; for most opioids, the half-life ranges from 2 to 4 hours.10 Heroin has a half-life of 30 minutes, but due to active metabolites its duration of action is 4 to 5 hours. Opioid metabolites can be detected in urine toxicology within approximately 1 to 2 days since last use.10
Chronic opioid use is associated with neurologic effects that change the function of areas of the brain that control pleasure/reward, stress, decision-making, and more. This leads to cravings, continued substance use, and dependence.11 After continued long-term use, patients report decreased euphoria, but typically they continue to use opioids to avoid withdrawal symptoms or worsening mood.
Criteria for opioid use disorder
In DSM-5, substance use disorders (SUDs)are no longer categorized as abuse or dependence.12 For opioids, the diagnosis is OUD. The Table12 outlines the DSM-5 criteria for OUD. Craving opioids is included for the first time in the OUD diagnosis. Having problems with the legal system is no longer considered a diagnostic criterion for OUD.
Continue to: A vulnerable population
A vulnerable population
As defined by Erik Erikson’s psychosocial stages of development, adolescents struggle between establishing their own identity vs role confusion.13 In an attempt to relate to peers or give in to peer pressure, some adolescents start by experimenting with nicotine, alcohol, and/or marijuana; however, some may move on to using other illicit drugs.14 Risk factors for the development of SUDs include early onset of substance use and a rapid progression through stages of substance use from experimentation to regular use, risky use, and dependence.15 In our case study, Ms. L’s substance use followed a similar pattern. Further, the comorbidity of SUDs and other psychiatric disorders may add a layer of complexity when caring for adolescents. Box 116-20 describes the relationship between comorbid psychiatric disorders and SUDs in adolescents.
Box 1
Disruptive behavior disorders are the most common coexisting psychiatric disorders in an adolescent with a substance use disorder (SUD), including opioid use disorder. These individuals typically present with aggression and other conduct disorder symptoms, and have early involvement with the legal system. Conversely, patients with conduct disorder are at high risk of early initiation of illicit substance use, including opioids. Early onset of substance use is a strong risk factor for developing an SUD.16
Mood disorders, particularly depression, can either precede or occur as a result of heavy and prolonged substance use.17 The estimated prevalence of major depressive disorder in individuals with an SUD is 24% to 50%. Among adolescents, an SUD is also a risk factor for suicidal ideation, suicide attempts, and completed suicide.18-20
Anxiety disorders, especially social phobia, and posttraumatic stress disorder are common in individuals with SUD.
Adolescents with SUD should be carefully evaluated for comorbid psychiatric disorders and treated accordingly.
Clinical manifestations
Common clinical manifestations of opioid use vary depending on when the patient is seen. An individual with OUD may appear acutely intoxicated, be in withdrawal, or show no effects. Chronic/prolonged use can lead to tolerance, such that a user needs to ingest larger amounts of the opioid to produce the same effects.
Acute intoxication can cause sedation, slurring of speech, and pinpoint pupils. Fresh injection sites may be visible on physical examination of IV users. The effects of acute intoxication usually depend on the half-life of the specific opioid and the individual’s tolerance.10 Tolerance to heroin can occur in 10 days and withdrawal can manifest in 3 to 7 hours after last use, depending on dose and purity.3 Tolerance can lead to unintentional overdose and death.
Withdrawal. Individuals experiencing withdrawal from opioids present with flu-like physical symptoms, including generalized body ache, rhinorrhea, diarrhea, goose bumps, lacrimation, and vomiting. Individuals also may experience irritability, restlessness, insomnia, anxiety, and depression during withdrawal.
Other manifestations. Excessive and chronic/prolonged opioid use can adversely impact socio-occupational functioning and cause academic decline in adolescents and youth. Personal relationships are significantly affected. Opioid users may have legal difficulties as a result of committing crimes such as theft, prostitution, or robbery in order to obtain opioids.
Continue to: Screening for OUD
Screening for OUD
Several screening tools are available to assess adolescents for SUDs, including OUD.
CRAFFT is a 6-item, clinician-administered screening tool that has been approved by American Academy of Pediatrics’ Committee on Substance Abuse for adolescents and young adults age <21.21-23 This commonly used tool can assess for alcohol, cannabis, and other drug use. A score ≥2 is considered positive for drug use, indicating that the individual would require further evaluation and assessment22,23 (Figure). There is also a self-administered CRAFFT questionnaire that can be completed by the patient.
NIDA-modified ASSIST. The American Psychiatric Association has adapted the National Institute on Drug Abuse (NIDA)-modified ASSIST. One version is designated for parents/guardians to administer to their children (age 6 to 17), and one is designated for adolescents (age 11 to 17) to self-administer.24,25 Each screening tool has 2 levels: Level 1 screens for substance use and other mental health symptoms, and Level 2 is more specific for substance use alone.
Drug Use Screening Inventory (DUSI) is a self-report questionnaire that has 149 items that assess the use of numerous drugs. It is designed to quantify the severity of consequences associated with drug and alcohol use.26,27
Problem-Oriented Screening Instrument for Teenagers (PO
Continue to: Personal Experience Screening Questionnaire (PESQ)...
Personal Experience Screening Questionnaire (PESQ) is a brief, 40-item, cost-effective, self-report questionnaire that can help identify adolescents (age 12 to 18) who should be referred for further evaluation.30
Addressing treatment expectations
For an adolescent with OUD, treatment should begin in the least restrictive environment that is perceived as safe for the patient. An adolescent’s readiness and motivation to achieve and maintain abstinence are crucial. Treatment planning should include the adolescent as well as his/her family to ensure they are able to verbalize their expectations. Start with a definitive treatment plan that addresses an individual’s needs. The plan should provide structure and an understanding of treatment expectations. The treatment team should clarify the realistic plan and goals based on empirical and clinical evidence. Treatment goals should include interventions to strengthen interpersonal relationships and assist with rehabilitation, such as establishing academic and/or vocational goals. Addressing readiness and working on a patient’s motivation is extremely important for most of these interventions.
In order for any intervention to be successful, clinicians need to establish and foster rapport with the adolescent. By law, substance use or behaviors related to substance use are not allowed to be shared outside the patient-clinician relationship, unless the adolescent gives consent or there are concerns that such behaviors might put the patient or others at risk. It is important to prime the adolescent and help them understand that any information pertaining to their safety or the safety of others may need to be shared outside the patient-clinician relationship.
Choosing an intervention
Less than 50% of a nationally representative sample of 345 addiction treatment programs serving adolescents and adults offer medications for treating OUD.31 Even in programs that offer pharmacotherapy, medications are significantly underutilized. Fewer than 30% of patients in addiction treatment programs receive medication, compared with 74% of patients receiving treatment for other mental health disorders.31 A
Psychotherapy may be used to treat OUD in adolescents. Several family therapies have been studied and are considered as critical psychotherapeutic interventions for treating SUDs, including structural family treatment and functional family therapy approaches.34 An integrated behavioral and family therapy model is also recommended for adolescent patients with SUDs. Cognitive distortions and use of self-deprecatory statements are common among adolescents.35 Therefore, using approaches of cognitive-behavioral therapy (CBT), or CBT plus motivational enhancement therapy, also might be effective for this population.36 The adolescent community reinforcement approach (A-CRA) is a behavioral treatment designed to help adolescents and their families learn how to lead a healthy and happy life without the use of drugs or alcohol by increasing access to social, familial, and educational/vocational reinforcers. Support groups and peer and family support should be encouraged as adjuncts to other interventions. In some areas, sober housing options for adolescents are also available.
Continue to: Harm-reduction strategies
Harm-reduction strategies. Although the primary goal of treatment for adolescents with OUD is to achieve and maintain abstinence from opioid use, implicit and explicit goals can be set. Short-term implicit goals may include harm-reduction strategies that emphasize decreasing the duration, frequency, and amount of substance use and limiting the chances of adverse effects, while the long-term explicit goal should be abstinence from opioid use.
Naloxone nasal spray is used as a harm-reduction strategy. It is an FDA-approved formulation that can reverse the effects of unintentional opioid overdoses and potentially prevent death from respiratory depression.37 Other harm-reduction strategies include needle exchange programs, which provide sterile needles to individuals who inject drugs in an effort to prevent or reduce the transmission of human immunodeficiency virus and other bloodborne viruses that can be spread via shared injection equipment. Fentanyl testing strips allow opioid users to test for the presence fentanyl and fentanyl analogs in the unregulated “street” opioid supply.
Pharmacologic interventions. Because there is limited empirical evidence on the efficacy of medication-assisted treatment (MAT) for adolescents with OUD, clinicians need to rely on evidence from research and experience with adults. Unfortunately, MAT is offered to adolescents considerably less often than it is to adults. Feder et al38 reported that only 2.4% of adolescents received MAT for heroin use and only 0.4% of adolescents received MAT for prescription opioid use, compared with 26.3% and 12% of adults, respectively.
Detoxification. Medications available for detoxification from opioids include opiates (such as methadone or buprenorphine) and clonidine (a central sympathomimetic). If the patient has used heroin for a short period (<1 year) and has no history of detoxification, consider a detoxification strategy with a longer-term taper (90 to 180 days) to allow for stabilization.
Maintenance treatment. Consider maintenance treatment for adolescents with a history of long-term opioid use and at least 2 prior short-term detoxification attempts or nonpharmacotherapy-based treatment within 12 months. Be sure to receive consent from a legal guardian and the patient. Maintenance treatment is usually recommended to continue for 1 to 6 years. Maintenance programs with longer durations have shown higher rates of abstinence, improved engagement, and retention in treatment.39
Continue to: According to guidelines from...
According to guidelines from the American Society of Addiction Medicine (ASAM), adolescents age >16 should be offered MAT; the first-line treatment is buprenorphine.40 To avoid risks of abuse and diversion, a combination of buprenorphine/naloxone may be administered.
Maintenance with buprenorphine
In order to prescribe and dispense buprenorphine, clinicians need to obtain a waiver from the Substance Abuse and Mental Health Services Administration. Before initiating buprenorphine, consider the type of opioid the individual used (short- or long-acting), the severity of the OUD, and the last reported use. The 3 phases of buprenorphine treatment are41:
- Induction phase. Buprenorphine can be initiated at 2 to 4 mg/d. Some patients may require up to 8 mg/d on the first day, which can be administered in divided doses.42 Evaluate and monitor patients carefully during the first few hours after the first dose. Patients should be in early withdrawal; otherwise, the buprenorphine might precipitate withdrawal. The induction phase can be completed in 2 to 4 days by titrating the dose so that the signs and symptoms of opioid withdrawal are minimal, and the patient is able to continue treatment. It may be helpful to have the patient’s legal guardian nearby in case the patient does not tolerate the medication or experiences withdrawal. The initial target dose for buprenorphine is approximately 12 to 16 mg/d.
- Stabilization phase. Patients no longer experience withdrawal symptoms and no longer have cravings. This phase can last 6 to 8 weeks. During this phase, patients should be seen weekly and doses should be adjusted if necessary. As a partial mu agonist, buprenorphine does not activate mu receptors fully and reaches a ceiling effect. Hence, doses >24 mg/d have limited added agonist properties.
- Maintenance phase. Because discontinuation of buprenorphine is associated with high relapse rates, patients may need to be maintained long-term on their stabilization dose, and for some patients, the length of time could be indefinite.39 During this phase, patients continue to undergo follow-up, but do so less frequently.
Methadone maintenance is generally not recommended for individuals age <18.
Preventing opioid diversion
Prescription medications that are kept in the home are a substantial source of opioids for adolescents. In 2014, 56% of 12th graders who did not need medications for medical purposes were able to acquire them from their friends or relatives; 36% of 12th graders used their own prescriptions.21 Limiting adolescents’ access to prescription opioids is the first line of prevention. Box 2 describes interventions and strategies to limit adolescents’ access to opioids.
Box 2
Many adolescents obtain opioids for recreational use from medications that were legitimately prescribed to family or friends. Both clinicians and parents/ guardians can take steps to reduce or prevent this type of diversion
Health care facilities. Regulating the number of pills dispensed to patients is crucial. It is highly recommended to prescribe only the minimal number of opioids necessary. In most cases, 3 to 7 days’ worth of opioids at a time might be sufficient, especially after surgical procedures.
Home. Families can limit adolescents’ access to prescription opioids in the home by keeping all medications in a lock box.
Proper disposal. Various entities offer locations for patients to drop off their unused opioids and other medications for safe disposal. These include police or fire departments and retail pharmacies. The US Drug Enforcement Administration sponsors a National Prescription Drug Take Back Day; see https://www.deadiversion.usdoj.gov/drug_disposal/takeback/index.html. The FDA also offers information on where and how to dispose of unused medicines at https://www.fda.gov/consumers/consumer-updates/where-and-how-dispose-unused-medicines.
CASE CONTINUED
Ms. L is initially prescribed, clonidine, 0.1 mg every 6 hours, to address opioid withdrawal. Clonidine is then tapered and maintained at 0.1 mg twice a day for irritability and impulse control. She is also prescribed sertraline, 100 mg/d, for depression and anxiety, and trazodone, 75 mg as needed at night, to assist with sleep.
Continue to: Following inpatient hospitalization...
Following inpatient hospitalization, during 12 weeks of partial hospital treatment, Ms. L participates in individual psychotherapy sessions 5 days/week; family therapy sessions once a week; and experiential therapy along with group sessions with other peers. She undergoes medication evaluations and adjustments on a weekly basis. Ms. L is now working at a store and is pursuing a high school equivalency certificate. She manages to avoid high-risk behaviors, although she reports having occasional cravings. Ms. L is actively involved in Narcotics Anonymous and has a sponsor. She has reconciled with her mother and moved back home, so she can stay away from her former acquaintances who are still using.
Bottom Line
Adolescents with opioid use disorder can benefit from an individualized treatment plan that includes psychosocial interventions, pharmacotherapy, or a combination of the two. Treatment planning should include the adolescent and his/her family to ensure they are able to verbalize their expectations. Treatment should focus on interventions that strengthen interpersonal relationships and assist with rehabilitation. Ongoing follow-up care is necessary for maintaining abstinence.
Related Resource
- Patkar AA, Weisler RH. Opioid abuse and overdose: Keep your patients safe. Current Psychiatry. 2017;16(8):8-12,14-16.
Drug Brand Names
Buprenorphine • Subutex, Sublocade
Buprenorphine/naloxone • Suboxone
Clonidine • Clorpres
Methadone • Methadose
Naloxone • Narcan
Oxycodone • OxyContin
Sertraline • Zoloft
Tramadol • Ultram
Trazodone • Desyrel, Oleptro
Ms. L, age 17, seeks treatment because she has an ongoing struggle with multiple substances, including benzodiazepines, heroin, alcohol, cannabis, and prescription opioids.
She reports that she was 13 when she first used a prescription opioid that was not prescribed for her. She also reports engaging in unsafe sexual practices while using these substances, and has been diagnosed and treated for a sexually transmitted disease. She dropped out of school and is estranged from her family. She says that for a long time she has felt depressed and that she uses drugs to “self-medicate my emotions.” She endorses high anxiety and lack of motivation. Ms. L also reports having several criminal charges for theft, assault, and exchanging sex for drugs. She has undergone 3 admissions for detoxification, but promptly resumed using drugs, primarily heroin and oxycodone, immediately after discharge. Ms. L meets DSM-5 criteria for opioid use disorder (OUD).
Ms. L’s case illustrates a disturbing trend in the current opioid epidemic in the United States. Nearly 11.8 million individuals age ≥12 reported misuse of opioids in the last year.1 Adolescents who misuse prescription or illicit opioids are more likely to be involved with the legal system due to truancy, running away from home, physical altercations, prostitution, exchanging sex for drugs, robbery, and gang involvement. Adolescents who use opioids may also struggle with academic decline, drop out of school early, be unable to maintain a job, and have relationship difficulties, especially with family members.
In this article, I describe the scope of OUD among adolescents, including epidemiology, clinical manifestations, screening tools, and treatment approaches.
Scope of the problem
According to the most recent Monitoring the Future survey of more than 42,500 8th, 10th, and 12th grade students, 2.7% of 12th graders reported prescription opioid misuse (reported in the survey as “narcotics other than heroin”) in the past year.2 In addition, 0.4% of 12th graders reported heroin use over the same period.2 Although the prevalence of opioid use among adolescents has been declining over the past 5 years,2 it still represents a serious health crisis.
Part of the issue may relate to easier access to more potent opioids. For example, heroin available today can be >4 times purer than it was in the past. In 2002, t
Between 1997 and 2012, the annual incidence of youth (age 15 to 19) hospitalizations for prescription opioid poisoning increased >170%.5 Approximately 6% to 9% of youth involved in risky opioid use develop OUD 6 to 12 months after s
Continue to: In recent years...
In recent years, deaths from drug overdose have increased for all age groups; however, limited data is available regarding adolescent overdose deaths. According to the Centers for Disease Control and Prevention (CDC), from 2015 to 2016, drug overdose death rates for persons age 15 to 24 increased to 28%.9
How opioids work
Opioids activate specific transmembrane neurotransmitter receptors, including mu, kappa, and delta, in the CNS and peripheral nervous system (PNS). This leads to activation of G protein–mediated intracellular signal transduction. Mainly it is activation of endogenous mu opioid receptors that mediates the reward, withdrawal, and analgesic effects of opioids. These effects depend on the location of mu receptors. In the CNS, activation of mu opioid receptors may cause miosis, respiratory depression, euphoria, and analgesia.10
Different opioids vary in terms of their half-life; for most opioids, the half-life ranges from 2 to 4 hours.10 Heroin has a half-life of 30 minutes, but due to active metabolites its duration of action is 4 to 5 hours. Opioid metabolites can be detected in urine toxicology within approximately 1 to 2 days since last use.10
Chronic opioid use is associated with neurologic effects that change the function of areas of the brain that control pleasure/reward, stress, decision-making, and more. This leads to cravings, continued substance use, and dependence.11 After continued long-term use, patients report decreased euphoria, but typically they continue to use opioids to avoid withdrawal symptoms or worsening mood.
Criteria for opioid use disorder
In DSM-5, substance use disorders (SUDs)are no longer categorized as abuse or dependence.12 For opioids, the diagnosis is OUD. The Table12 outlines the DSM-5 criteria for OUD. Craving opioids is included for the first time in the OUD diagnosis. Having problems with the legal system is no longer considered a diagnostic criterion for OUD.
Continue to: A vulnerable population
A vulnerable population
As defined by Erik Erikson’s psychosocial stages of development, adolescents struggle between establishing their own identity vs role confusion.13 In an attempt to relate to peers or give in to peer pressure, some adolescents start by experimenting with nicotine, alcohol, and/or marijuana; however, some may move on to using other illicit drugs.14 Risk factors for the development of SUDs include early onset of substance use and a rapid progression through stages of substance use from experimentation to regular use, risky use, and dependence.15 In our case study, Ms. L’s substance use followed a similar pattern. Further, the comorbidity of SUDs and other psychiatric disorders may add a layer of complexity when caring for adolescents. Box 116-20 describes the relationship between comorbid psychiatric disorders and SUDs in adolescents.
Box 1
Disruptive behavior disorders are the most common coexisting psychiatric disorders in an adolescent with a substance use disorder (SUD), including opioid use disorder. These individuals typically present with aggression and other conduct disorder symptoms, and have early involvement with the legal system. Conversely, patients with conduct disorder are at high risk of early initiation of illicit substance use, including opioids. Early onset of substance use is a strong risk factor for developing an SUD.16
Mood disorders, particularly depression, can either precede or occur as a result of heavy and prolonged substance use.17 The estimated prevalence of major depressive disorder in individuals with an SUD is 24% to 50%. Among adolescents, an SUD is also a risk factor for suicidal ideation, suicide attempts, and completed suicide.18-20
Anxiety disorders, especially social phobia, and posttraumatic stress disorder are common in individuals with SUD.
Adolescents with SUD should be carefully evaluated for comorbid psychiatric disorders and treated accordingly.
Clinical manifestations
Common clinical manifestations of opioid use vary depending on when the patient is seen. An individual with OUD may appear acutely intoxicated, be in withdrawal, or show no effects. Chronic/prolonged use can lead to tolerance, such that a user needs to ingest larger amounts of the opioid to produce the same effects.
Acute intoxication can cause sedation, slurring of speech, and pinpoint pupils. Fresh injection sites may be visible on physical examination of IV users. The effects of acute intoxication usually depend on the half-life of the specific opioid and the individual’s tolerance.10 Tolerance to heroin can occur in 10 days and withdrawal can manifest in 3 to 7 hours after last use, depending on dose and purity.3 Tolerance can lead to unintentional overdose and death.
Withdrawal. Individuals experiencing withdrawal from opioids present with flu-like physical symptoms, including generalized body ache, rhinorrhea, diarrhea, goose bumps, lacrimation, and vomiting. Individuals also may experience irritability, restlessness, insomnia, anxiety, and depression during withdrawal.
Other manifestations. Excessive and chronic/prolonged opioid use can adversely impact socio-occupational functioning and cause academic decline in adolescents and youth. Personal relationships are significantly affected. Opioid users may have legal difficulties as a result of committing crimes such as theft, prostitution, or robbery in order to obtain opioids.
Continue to: Screening for OUD
Screening for OUD
Several screening tools are available to assess adolescents for SUDs, including OUD.
CRAFFT is a 6-item, clinician-administered screening tool that has been approved by American Academy of Pediatrics’ Committee on Substance Abuse for adolescents and young adults age <21.21-23 This commonly used tool can assess for alcohol, cannabis, and other drug use. A score ≥2 is considered positive for drug use, indicating that the individual would require further evaluation and assessment22,23 (Figure). There is also a self-administered CRAFFT questionnaire that can be completed by the patient.
NIDA-modified ASSIST. The American Psychiatric Association has adapted the National Institute on Drug Abuse (NIDA)-modified ASSIST. One version is designated for parents/guardians to administer to their children (age 6 to 17), and one is designated for adolescents (age 11 to 17) to self-administer.24,25 Each screening tool has 2 levels: Level 1 screens for substance use and other mental health symptoms, and Level 2 is more specific for substance use alone.
Drug Use Screening Inventory (DUSI) is a self-report questionnaire that has 149 items that assess the use of numerous drugs. It is designed to quantify the severity of consequences associated with drug and alcohol use.26,27
Problem-Oriented Screening Instrument for Teenagers (PO
Continue to: Personal Experience Screening Questionnaire (PESQ)...
Personal Experience Screening Questionnaire (PESQ) is a brief, 40-item, cost-effective, self-report questionnaire that can help identify adolescents (age 12 to 18) who should be referred for further evaluation.30
Addressing treatment expectations
For an adolescent with OUD, treatment should begin in the least restrictive environment that is perceived as safe for the patient. An adolescent’s readiness and motivation to achieve and maintain abstinence are crucial. Treatment planning should include the adolescent as well as his/her family to ensure they are able to verbalize their expectations. Start with a definitive treatment plan that addresses an individual’s needs. The plan should provide structure and an understanding of treatment expectations. The treatment team should clarify the realistic plan and goals based on empirical and clinical evidence. Treatment goals should include interventions to strengthen interpersonal relationships and assist with rehabilitation, such as establishing academic and/or vocational goals. Addressing readiness and working on a patient’s motivation is extremely important for most of these interventions.
In order for any intervention to be successful, clinicians need to establish and foster rapport with the adolescent. By law, substance use or behaviors related to substance use are not allowed to be shared outside the patient-clinician relationship, unless the adolescent gives consent or there are concerns that such behaviors might put the patient or others at risk. It is important to prime the adolescent and help them understand that any information pertaining to their safety or the safety of others may need to be shared outside the patient-clinician relationship.
Choosing an intervention
Less than 50% of a nationally representative sample of 345 addiction treatment programs serving adolescents and adults offer medications for treating OUD.31 Even in programs that offer pharmacotherapy, medications are significantly underutilized. Fewer than 30% of patients in addiction treatment programs receive medication, compared with 74% of patients receiving treatment for other mental health disorders.31 A
Psychotherapy may be used to treat OUD in adolescents. Several family therapies have been studied and are considered as critical psychotherapeutic interventions for treating SUDs, including structural family treatment and functional family therapy approaches.34 An integrated behavioral and family therapy model is also recommended for adolescent patients with SUDs. Cognitive distortions and use of self-deprecatory statements are common among adolescents.35 Therefore, using approaches of cognitive-behavioral therapy (CBT), or CBT plus motivational enhancement therapy, also might be effective for this population.36 The adolescent community reinforcement approach (A-CRA) is a behavioral treatment designed to help adolescents and their families learn how to lead a healthy and happy life without the use of drugs or alcohol by increasing access to social, familial, and educational/vocational reinforcers. Support groups and peer and family support should be encouraged as adjuncts to other interventions. In some areas, sober housing options for adolescents are also available.
Continue to: Harm-reduction strategies
Harm-reduction strategies. Although the primary goal of treatment for adolescents with OUD is to achieve and maintain abstinence from opioid use, implicit and explicit goals can be set. Short-term implicit goals may include harm-reduction strategies that emphasize decreasing the duration, frequency, and amount of substance use and limiting the chances of adverse effects, while the long-term explicit goal should be abstinence from opioid use.
Naloxone nasal spray is used as a harm-reduction strategy. It is an FDA-approved formulation that can reverse the effects of unintentional opioid overdoses and potentially prevent death from respiratory depression.37 Other harm-reduction strategies include needle exchange programs, which provide sterile needles to individuals who inject drugs in an effort to prevent or reduce the transmission of human immunodeficiency virus and other bloodborne viruses that can be spread via shared injection equipment. Fentanyl testing strips allow opioid users to test for the presence fentanyl and fentanyl analogs in the unregulated “street” opioid supply.
Pharmacologic interventions. Because there is limited empirical evidence on the efficacy of medication-assisted treatment (MAT) for adolescents with OUD, clinicians need to rely on evidence from research and experience with adults. Unfortunately, MAT is offered to adolescents considerably less often than it is to adults. Feder et al38 reported that only 2.4% of adolescents received MAT for heroin use and only 0.4% of adolescents received MAT for prescription opioid use, compared with 26.3% and 12% of adults, respectively.
Detoxification. Medications available for detoxification from opioids include opiates (such as methadone or buprenorphine) and clonidine (a central sympathomimetic). If the patient has used heroin for a short period (<1 year) and has no history of detoxification, consider a detoxification strategy with a longer-term taper (90 to 180 days) to allow for stabilization.
Maintenance treatment. Consider maintenance treatment for adolescents with a history of long-term opioid use and at least 2 prior short-term detoxification attempts or nonpharmacotherapy-based treatment within 12 months. Be sure to receive consent from a legal guardian and the patient. Maintenance treatment is usually recommended to continue for 1 to 6 years. Maintenance programs with longer durations have shown higher rates of abstinence, improved engagement, and retention in treatment.39
Continue to: According to guidelines from...
According to guidelines from the American Society of Addiction Medicine (ASAM), adolescents age >16 should be offered MAT; the first-line treatment is buprenorphine.40 To avoid risks of abuse and diversion, a combination of buprenorphine/naloxone may be administered.
Maintenance with buprenorphine
In order to prescribe and dispense buprenorphine, clinicians need to obtain a waiver from the Substance Abuse and Mental Health Services Administration. Before initiating buprenorphine, consider the type of opioid the individual used (short- or long-acting), the severity of the OUD, and the last reported use. The 3 phases of buprenorphine treatment are41:
- Induction phase. Buprenorphine can be initiated at 2 to 4 mg/d. Some patients may require up to 8 mg/d on the first day, which can be administered in divided doses.42 Evaluate and monitor patients carefully during the first few hours after the first dose. Patients should be in early withdrawal; otherwise, the buprenorphine might precipitate withdrawal. The induction phase can be completed in 2 to 4 days by titrating the dose so that the signs and symptoms of opioid withdrawal are minimal, and the patient is able to continue treatment. It may be helpful to have the patient’s legal guardian nearby in case the patient does not tolerate the medication or experiences withdrawal. The initial target dose for buprenorphine is approximately 12 to 16 mg/d.
- Stabilization phase. Patients no longer experience withdrawal symptoms and no longer have cravings. This phase can last 6 to 8 weeks. During this phase, patients should be seen weekly and doses should be adjusted if necessary. As a partial mu agonist, buprenorphine does not activate mu receptors fully and reaches a ceiling effect. Hence, doses >24 mg/d have limited added agonist properties.
- Maintenance phase. Because discontinuation of buprenorphine is associated with high relapse rates, patients may need to be maintained long-term on their stabilization dose, and for some patients, the length of time could be indefinite.39 During this phase, patients continue to undergo follow-up, but do so less frequently.
Methadone maintenance is generally not recommended for individuals age <18.
Preventing opioid diversion
Prescription medications that are kept in the home are a substantial source of opioids for adolescents. In 2014, 56% of 12th graders who did not need medications for medical purposes were able to acquire them from their friends or relatives; 36% of 12th graders used their own prescriptions.21 Limiting adolescents’ access to prescription opioids is the first line of prevention. Box 2 describes interventions and strategies to limit adolescents’ access to opioids.
Box 2
Many adolescents obtain opioids for recreational use from medications that were legitimately prescribed to family or friends. Both clinicians and parents/ guardians can take steps to reduce or prevent this type of diversion
Health care facilities. Regulating the number of pills dispensed to patients is crucial. It is highly recommended to prescribe only the minimal number of opioids necessary. In most cases, 3 to 7 days’ worth of opioids at a time might be sufficient, especially after surgical procedures.
Home. Families can limit adolescents’ access to prescription opioids in the home by keeping all medications in a lock box.
Proper disposal. Various entities offer locations for patients to drop off their unused opioids and other medications for safe disposal. These include police or fire departments and retail pharmacies. The US Drug Enforcement Administration sponsors a National Prescription Drug Take Back Day; see https://www.deadiversion.usdoj.gov/drug_disposal/takeback/index.html. The FDA also offers information on where and how to dispose of unused medicines at https://www.fda.gov/consumers/consumer-updates/where-and-how-dispose-unused-medicines.
CASE CONTINUED
Ms. L is initially prescribed, clonidine, 0.1 mg every 6 hours, to address opioid withdrawal. Clonidine is then tapered and maintained at 0.1 mg twice a day for irritability and impulse control. She is also prescribed sertraline, 100 mg/d, for depression and anxiety, and trazodone, 75 mg as needed at night, to assist with sleep.
Continue to: Following inpatient hospitalization...
Following inpatient hospitalization, during 12 weeks of partial hospital treatment, Ms. L participates in individual psychotherapy sessions 5 days/week; family therapy sessions once a week; and experiential therapy along with group sessions with other peers. She undergoes medication evaluations and adjustments on a weekly basis. Ms. L is now working at a store and is pursuing a high school equivalency certificate. She manages to avoid high-risk behaviors, although she reports having occasional cravings. Ms. L is actively involved in Narcotics Anonymous and has a sponsor. She has reconciled with her mother and moved back home, so she can stay away from her former acquaintances who are still using.
Bottom Line
Adolescents with opioid use disorder can benefit from an individualized treatment plan that includes psychosocial interventions, pharmacotherapy, or a combination of the two. Treatment planning should include the adolescent and his/her family to ensure they are able to verbalize their expectations. Treatment should focus on interventions that strengthen interpersonal relationships and assist with rehabilitation. Ongoing follow-up care is necessary for maintaining abstinence.
Related Resource
- Patkar AA, Weisler RH. Opioid abuse and overdose: Keep your patients safe. Current Psychiatry. 2017;16(8):8-12,14-16.
Drug Brand Names
Buprenorphine • Subutex, Sublocade
Buprenorphine/naloxone • Suboxone
Clonidine • Clorpres
Methadone • Methadose
Naloxone • Narcan
Oxycodone • OxyContin
Sertraline • Zoloft
Tramadol • Ultram
Trazodone • Desyrel, Oleptro
1. Davis JP, Prindle JJ, Eddie D, et al. Addressing the opioid epidemic with behavioral interventions for adolescents and young adults: a quasi-experimental design. J Consult Clin Psychol. 2019;87(10):941-951.
2. National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services. Monitoring the Future Survey: High School and Youth Trends. https://www.drugabuse.gov/publications/drugfacts/monitoring-future-survey-high-school-youth-trends. Updated December 2019. Accessed January 13, 2020.
3. Hopfer CJ, Khuri E, Crowley TJ. Treating adolescent heroin use. J Am Acad Child Adolesc Psychiatry. 2003;42(5):609-611.
4. US Department of Justice, Drug Enforcement Agency, Diversion Control Division. https://www.deadiversion.usdoj.gov/. Accessed January 21, 2020.
5. Gaither JR, Leventhal JM, Ryan SA, et al. National trends in hospitalizations for opioid poisonings among children and adolescents, 1997-2012. JAMA Pediatr. 2016;170(12):1195-1201.
6. Parker MA, Anthony JC. Epidemiological evidence on extra-medical use of prescription pain relievers: transitions from newly incident use to dependence among 12-21 year olds in United States using meta-analysis, 2002-13. Peer J. 2015;3:e1340. doi: 10.7717/peerj.1340. eCollection 2015.
7. Subramaniam GA, Fishman MJ, Woody G. Treatment of opioid-dependent adolescents and young adults with buprenorphine. Curr Psychiatry Rep. 2009;11(5):360-363.
8. Borodovsky JT, Levy S, Fishman M. Buprenorphine treatment for adolescents and young adults with opioid use disorders: a narrative review. J Addict Med. 2018;12(3):170-183.
9. Centers for Disease Control and Prevention: National Center for Health Statistics. Drug overdose deaths in the United States, 1999-2016. https://www.cdc.gov/nchs/products/databriefs/db294.htm. Published December 2017. Accessed January 15, 2020.
10. Strain E. Opioid use disorder: epidemiology, pharmacology, clinical manifestation, course, screening, assessment, diagnosis. https://www.uptodate.com/contents/opioid-use-disorder-epidemiology-pharmacology-clinical-manifestations-course-screening-assessment-and-diagnosis. Updated August 15, 2019. Accessed January 21, 2020.
11. American Academy of Pediatrics Committee on Substance Use and Prevention. Policy statement: medication-assisted treatment of adolescents with opioid use disorder. Pediatrics. 2016;138(3):e20161893. doi: https://doi.org/10.1542/peds.2016-1893.
12. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013:514.
13. Sadock BJ, Sadock VA. Chapter 6: Theories of personality and psychopathology. In: Sadock BJ, Sadock VA, eds. Kaplan and Sadock’s synopsis of psychiatry: behavioral sciences/clinical. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:209.
14. Kandel DB. Stages and pathways of drug involvement: examining the gateway hypothesis. Cambridge, United Kingdom: Cambridge University Press; 2002.
15. Robins LN, McEvoy L. Conduct problems as predictors of substance abuse. In: Robins LN, Rutter M, eds. Straight and devious pathways from childhood to adulthood. Cambridge, United Kingdom: Cambridge University Press; 1990;182-204.
16. Hopfer C, Salomonsen-Sautel S, Mikulich-Gilbertson S, et al. Conduct disorder and initiation of substance use: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2013;52(5):511-518.e4.
17. Armstrong TD, Costello EJ. Community studies on adolescent substance use, abuse, or dependence and psychiatric comorbidity. J Consult Clin Psychol. 2002;70(6):1224-1239.
18. Crumley FE. Substance abuse and adolescent suicidal behavior. JAMA. 1990;263(22):3051-3056.
19. Lewinsohn PM, Rohde P, Seeley JR. Adolescent suicidal ideation and attempts: prevalence, risk factors, and clinical implications. Clinical Psychology: Science and Practice. 1996;3(1):25-46.
20. Kendler KS, Bulik CM, Silberg J, et al. Childhood sexual abuse and adult psychiatric and substance use disorder in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry. 2000;57(10):953-959.
21. Yule AM, Wilens TE, Rausch PK. The opioid epidemic: what a child psychiatrist is to do? J Am Acad Child Adolesc Psychiatry. 2017;56(7);541-543.
22. CRAFFT. https://crafft.org. Accessed January 21, 2020.
23. Knight JR, Sherritt L, Harris SK, et al. Validity of brief alcohol screening tests among adolescents: a comparison of the AUDIT, POSIT, CAGE, and CRAFFT. Alcohol Clin Exp Res. 2003;27(1):67-73.
24. American Psychiatric Association. Online assessment measures. https://www.psychiatry.org/psychiatrists/practice/dsm/educational-resources/assessment-measures. Accessed January 15, 2020.
25. National Institute of Drug Abuse. American Psychiatric Association adapted NIDA modified ASSIST tools. https://www.drugabuse.gov/nidamed-medical-health-professionals/tool-resources-your-practice/screening-assessment-drug-testing-resources/american-psychiatric-association-adapted-nida. Updated November 15, 2015. Accessed January 21, 2020.
26. Canada’s Mental Health & Addiction Network. Drug Use Screening Inventory (DUSI). https://www.porticonetwork.ca/web/knowledgex-archive/amh-specialists/screening-for-cd-in-youth/screening-both-mh-sud/dusi. Published 2009. Accessed January 21, 2020.
27. Tarter RE. Evaluation and treatment of adolescent substance abuse: a decision tree method. Am J Drug Alcohol Abuse. 1990;16(1-2):1-46.
28. Klitzner M, Gruenwald PJ, Taff GA, et al. The adolescent assessment referral system-final report. National Institute on Drug Abuse; Rockville, MD: 1993. NIDA Contract No. 271-89-8252.
29. Slesnick N, Tonigan JS. Assessment of alcohol and other drug use by runaway youths: a test-retest study of the Form 90. Alcohol Treat Q. 2004;22(2):21-34.
30. Winters KC, Kaminer Y. Screening and assessing adolescent substance use disorders in clinical populations. J Am Acad Child Adolesc Psychiatry. 2008;47(7):740-744.
31. Knudsen HK, Abraham AJ, Roman PM. Adoption and implementation of medications in addiction treatment programs. J Addict Med. 2011;5(1):21-27.
32. Deas D, Thomas SE. An overview of controlled study of adolescent substance abuse treatment. Am J Addiction. 2001;10(2):178-189.
33. William RJ, Chang, SY. A comprehensive and comparative review of adolescent substance abuse treatment outcome. Clinical Psychology: Science and Practice. 2000;7(2):138-166.
34. Bukstein OG, Work Group on Quality Issues. Practice parameters for the assessment and treatment of children and adolescents with substance use disorders. J Am Acad Child Adolesc Psychiatry. 2005;44(6):609-621.
35. Van Hasselt VB, Null JA, Kempton T, et al. Social skills and depression in adolescent substance abusers. Addict Behav. 1993;18(1):9-18.
36. Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) study: main findings from two randomized trials. J Subst Abuse Treat. 2004;27(3):197-213.
37. US Food and Drug Administration. Information about naloxone. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-naloxone. Updated December 19, 2019. Accessed January 21, 2020.
38. Feder KA, Krawcyzk N, Saloner, B. Medication-assisted treatment for adolescents in specialty treatment for opioid use disorder. J Adolesc Health. 2018;60(6):747-750.
39. Woody GE, Poole SA, Subramaniam G, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA. 2008;300(17):2003-2011.
40. US Department of Health and Human Services. Substance Abuse and Mental Health Ser-vices Administration. Medication-assisted treatment for opioid addiction in opioid treatment programs: a treatment improvement protocol TIP 43. https://www.asam.org/docs/advocacy/samhsa_tip43_matforopioidaddiction.pdf?sfvrsn=0. Published 2005. Accessed January 15, 2020.
41. US Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment (MAT). https://www.samhsa.gov/medication-assisted-treatment. Updated September 9, 2019. Accessed January 21, 2020.
42. Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend. 2003;70(suppl 2):S59-S77.
1. Davis JP, Prindle JJ, Eddie D, et al. Addressing the opioid epidemic with behavioral interventions for adolescents and young adults: a quasi-experimental design. J Consult Clin Psychol. 2019;87(10):941-951.
2. National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services. Monitoring the Future Survey: High School and Youth Trends. https://www.drugabuse.gov/publications/drugfacts/monitoring-future-survey-high-school-youth-trends. Updated December 2019. Accessed January 13, 2020.
3. Hopfer CJ, Khuri E, Crowley TJ. Treating adolescent heroin use. J Am Acad Child Adolesc Psychiatry. 2003;42(5):609-611.
4. US Department of Justice, Drug Enforcement Agency, Diversion Control Division. https://www.deadiversion.usdoj.gov/. Accessed January 21, 2020.
5. Gaither JR, Leventhal JM, Ryan SA, et al. National trends in hospitalizations for opioid poisonings among children and adolescents, 1997-2012. JAMA Pediatr. 2016;170(12):1195-1201.
6. Parker MA, Anthony JC. Epidemiological evidence on extra-medical use of prescription pain relievers: transitions from newly incident use to dependence among 12-21 year olds in United States using meta-analysis, 2002-13. Peer J. 2015;3:e1340. doi: 10.7717/peerj.1340. eCollection 2015.
7. Subramaniam GA, Fishman MJ, Woody G. Treatment of opioid-dependent adolescents and young adults with buprenorphine. Curr Psychiatry Rep. 2009;11(5):360-363.
8. Borodovsky JT, Levy S, Fishman M. Buprenorphine treatment for adolescents and young adults with opioid use disorders: a narrative review. J Addict Med. 2018;12(3):170-183.
9. Centers for Disease Control and Prevention: National Center for Health Statistics. Drug overdose deaths in the United States, 1999-2016. https://www.cdc.gov/nchs/products/databriefs/db294.htm. Published December 2017. Accessed January 15, 2020.
10. Strain E. Opioid use disorder: epidemiology, pharmacology, clinical manifestation, course, screening, assessment, diagnosis. https://www.uptodate.com/contents/opioid-use-disorder-epidemiology-pharmacology-clinical-manifestations-course-screening-assessment-and-diagnosis. Updated August 15, 2019. Accessed January 21, 2020.
11. American Academy of Pediatrics Committee on Substance Use and Prevention. Policy statement: medication-assisted treatment of adolescents with opioid use disorder. Pediatrics. 2016;138(3):e20161893. doi: https://doi.org/10.1542/peds.2016-1893.
12. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013:514.
13. Sadock BJ, Sadock VA. Chapter 6: Theories of personality and psychopathology. In: Sadock BJ, Sadock VA, eds. Kaplan and Sadock’s synopsis of psychiatry: behavioral sciences/clinical. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:209.
14. Kandel DB. Stages and pathways of drug involvement: examining the gateway hypothesis. Cambridge, United Kingdom: Cambridge University Press; 2002.
15. Robins LN, McEvoy L. Conduct problems as predictors of substance abuse. In: Robins LN, Rutter M, eds. Straight and devious pathways from childhood to adulthood. Cambridge, United Kingdom: Cambridge University Press; 1990;182-204.
16. Hopfer C, Salomonsen-Sautel S, Mikulich-Gilbertson S, et al. Conduct disorder and initiation of substance use: a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry. 2013;52(5):511-518.e4.
17. Armstrong TD, Costello EJ. Community studies on adolescent substance use, abuse, or dependence and psychiatric comorbidity. J Consult Clin Psychol. 2002;70(6):1224-1239.
18. Crumley FE. Substance abuse and adolescent suicidal behavior. JAMA. 1990;263(22):3051-3056.
19. Lewinsohn PM, Rohde P, Seeley JR. Adolescent suicidal ideation and attempts: prevalence, risk factors, and clinical implications. Clinical Psychology: Science and Practice. 1996;3(1):25-46.
20. Kendler KS, Bulik CM, Silberg J, et al. Childhood sexual abuse and adult psychiatric and substance use disorder in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry. 2000;57(10):953-959.
21. Yule AM, Wilens TE, Rausch PK. The opioid epidemic: what a child psychiatrist is to do? J Am Acad Child Adolesc Psychiatry. 2017;56(7);541-543.
22. CRAFFT. https://crafft.org. Accessed January 21, 2020.
23. Knight JR, Sherritt L, Harris SK, et al. Validity of brief alcohol screening tests among adolescents: a comparison of the AUDIT, POSIT, CAGE, and CRAFFT. Alcohol Clin Exp Res. 2003;27(1):67-73.
24. American Psychiatric Association. Online assessment measures. https://www.psychiatry.org/psychiatrists/practice/dsm/educational-resources/assessment-measures. Accessed January 15, 2020.
25. National Institute of Drug Abuse. American Psychiatric Association adapted NIDA modified ASSIST tools. https://www.drugabuse.gov/nidamed-medical-health-professionals/tool-resources-your-practice/screening-assessment-drug-testing-resources/american-psychiatric-association-adapted-nida. Updated November 15, 2015. Accessed January 21, 2020.
26. Canada’s Mental Health & Addiction Network. Drug Use Screening Inventory (DUSI). https://www.porticonetwork.ca/web/knowledgex-archive/amh-specialists/screening-for-cd-in-youth/screening-both-mh-sud/dusi. Published 2009. Accessed January 21, 2020.
27. Tarter RE. Evaluation and treatment of adolescent substance abuse: a decision tree method. Am J Drug Alcohol Abuse. 1990;16(1-2):1-46.
28. Klitzner M, Gruenwald PJ, Taff GA, et al. The adolescent assessment referral system-final report. National Institute on Drug Abuse; Rockville, MD: 1993. NIDA Contract No. 271-89-8252.
29. Slesnick N, Tonigan JS. Assessment of alcohol and other drug use by runaway youths: a test-retest study of the Form 90. Alcohol Treat Q. 2004;22(2):21-34.
30. Winters KC, Kaminer Y. Screening and assessing adolescent substance use disorders in clinical populations. J Am Acad Child Adolesc Psychiatry. 2008;47(7):740-744.
31. Knudsen HK, Abraham AJ, Roman PM. Adoption and implementation of medications in addiction treatment programs. J Addict Med. 2011;5(1):21-27.
32. Deas D, Thomas SE. An overview of controlled study of adolescent substance abuse treatment. Am J Addiction. 2001;10(2):178-189.
33. William RJ, Chang, SY. A comprehensive and comparative review of adolescent substance abuse treatment outcome. Clinical Psychology: Science and Practice. 2000;7(2):138-166.
34. Bukstein OG, Work Group on Quality Issues. Practice parameters for the assessment and treatment of children and adolescents with substance use disorders. J Am Acad Child Adolesc Psychiatry. 2005;44(6):609-621.
35. Van Hasselt VB, Null JA, Kempton T, et al. Social skills and depression in adolescent substance abusers. Addict Behav. 1993;18(1):9-18.
36. Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) study: main findings from two randomized trials. J Subst Abuse Treat. 2004;27(3):197-213.
37. US Food and Drug Administration. Information about naloxone. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-naloxone. Updated December 19, 2019. Accessed January 21, 2020.
38. Feder KA, Krawcyzk N, Saloner, B. Medication-assisted treatment for adolescents in specialty treatment for opioid use disorder. J Adolesc Health. 2018;60(6):747-750.
39. Woody GE, Poole SA, Subramaniam G, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA. 2008;300(17):2003-2011.
40. US Department of Health and Human Services. Substance Abuse and Mental Health Ser-vices Administration. Medication-assisted treatment for opioid addiction in opioid treatment programs: a treatment improvement protocol TIP 43. https://www.asam.org/docs/advocacy/samhsa_tip43_matforopioidaddiction.pdf?sfvrsn=0. Published 2005. Accessed January 15, 2020.
41. US Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment (MAT). https://www.samhsa.gov/medication-assisted-treatment. Updated September 9, 2019. Accessed January 21, 2020.
42. Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend. 2003;70(suppl 2):S59-S77.
CDC: Opioid prescribing and use rates down since 2010
Trends in opioid prescribing and use from 2010 to 2016 offer some encouragement, but opioid-attributable deaths continued to increase over that period, according to the Centers for Disease Control and Prevention.
Prescribing rates dropped during that period, as did daily opioid dosage rates and the percentage of patients with high daily opioid dosages, Gail K. Strickler, PhD, of the Institute for Behavioral Health at Brandeis University in Waltham, Mass., and associates wrote in MMWR Surveillance Summaries.
Their analysis involved 11 of the 12 states (Washington was unable to provide data for the analysis) participating in the CDC’s Prescription Behavior Surveillance System, which uses data from the states’ prescription drug monitoring programs. The 11 states represented about 38% of the U.S. population in 2016.
The opioid prescribing rate fell in 10 of those 11 states, with declines varying from 3.4% in Idaho to 33.0% in Ohio. Prescribing went up in Texas by 11.3%, but the state only had data available for 2015 and 2016. Three other states – Delaware, Florida, and Idaho – were limited to data from 2012 to 2016, the investigators noted.
As for the other measures, all states showed declines for the mean daily opioid dosage. Texas had the smallest drop at 2.9% and Florida saw the largest, at 27.4%. All states also had reductions in the percentage of patients with high daily opioid dosage, with decreases varying from 5.7% in Idaho to 43.9% in Louisiana, Dr. Strickler and associates reported. A high daily dosage was defined as at least 90 morphine milligram equivalents for all class II-V opioid drugs.
“Despite these favorable trends ... opioid overdose deaths attributable to the most commonly prescribed opioids, the natural and semisynthetics (e.g., morphine and oxycodone), increased during 2010-2016,” they said.
It is possible that a change in mortality is lagging “behind changes in prescribing behaviors” or that “the trend in deaths related to these types of opioids has been driven by factors other than prescription opioid misuse rates, such as increasing mortality from heroin, which is frequently classified as morphine or found concomitantly with morphine postmortem, and a spike in deaths involving illicitly manufactured fentanyl combined with heroin and prescribed opioids since 2013,” the investigators suggested.
SOURCE: Strickler GK et al. MMWR Surveill Summ. 2020 Jan 31;69(1):1-14.
Trends in opioid prescribing and use from 2010 to 2016 offer some encouragement, but opioid-attributable deaths continued to increase over that period, according to the Centers for Disease Control and Prevention.
Prescribing rates dropped during that period, as did daily opioid dosage rates and the percentage of patients with high daily opioid dosages, Gail K. Strickler, PhD, of the Institute for Behavioral Health at Brandeis University in Waltham, Mass., and associates wrote in MMWR Surveillance Summaries.
Their analysis involved 11 of the 12 states (Washington was unable to provide data for the analysis) participating in the CDC’s Prescription Behavior Surveillance System, which uses data from the states’ prescription drug monitoring programs. The 11 states represented about 38% of the U.S. population in 2016.
The opioid prescribing rate fell in 10 of those 11 states, with declines varying from 3.4% in Idaho to 33.0% in Ohio. Prescribing went up in Texas by 11.3%, but the state only had data available for 2015 and 2016. Three other states – Delaware, Florida, and Idaho – were limited to data from 2012 to 2016, the investigators noted.
As for the other measures, all states showed declines for the mean daily opioid dosage. Texas had the smallest drop at 2.9% and Florida saw the largest, at 27.4%. All states also had reductions in the percentage of patients with high daily opioid dosage, with decreases varying from 5.7% in Idaho to 43.9% in Louisiana, Dr. Strickler and associates reported. A high daily dosage was defined as at least 90 morphine milligram equivalents for all class II-V opioid drugs.
“Despite these favorable trends ... opioid overdose deaths attributable to the most commonly prescribed opioids, the natural and semisynthetics (e.g., morphine and oxycodone), increased during 2010-2016,” they said.
It is possible that a change in mortality is lagging “behind changes in prescribing behaviors” or that “the trend in deaths related to these types of opioids has been driven by factors other than prescription opioid misuse rates, such as increasing mortality from heroin, which is frequently classified as morphine or found concomitantly with morphine postmortem, and a spike in deaths involving illicitly manufactured fentanyl combined with heroin and prescribed opioids since 2013,” the investigators suggested.
SOURCE: Strickler GK et al. MMWR Surveill Summ. 2020 Jan 31;69(1):1-14.
Trends in opioid prescribing and use from 2010 to 2016 offer some encouragement, but opioid-attributable deaths continued to increase over that period, according to the Centers for Disease Control and Prevention.
Prescribing rates dropped during that period, as did daily opioid dosage rates and the percentage of patients with high daily opioid dosages, Gail K. Strickler, PhD, of the Institute for Behavioral Health at Brandeis University in Waltham, Mass., and associates wrote in MMWR Surveillance Summaries.
Their analysis involved 11 of the 12 states (Washington was unable to provide data for the analysis) participating in the CDC’s Prescription Behavior Surveillance System, which uses data from the states’ prescription drug monitoring programs. The 11 states represented about 38% of the U.S. population in 2016.
The opioid prescribing rate fell in 10 of those 11 states, with declines varying from 3.4% in Idaho to 33.0% in Ohio. Prescribing went up in Texas by 11.3%, but the state only had data available for 2015 and 2016. Three other states – Delaware, Florida, and Idaho – were limited to data from 2012 to 2016, the investigators noted.
As for the other measures, all states showed declines for the mean daily opioid dosage. Texas had the smallest drop at 2.9% and Florida saw the largest, at 27.4%. All states also had reductions in the percentage of patients with high daily opioid dosage, with decreases varying from 5.7% in Idaho to 43.9% in Louisiana, Dr. Strickler and associates reported. A high daily dosage was defined as at least 90 morphine milligram equivalents for all class II-V opioid drugs.
“Despite these favorable trends ... opioid overdose deaths attributable to the most commonly prescribed opioids, the natural and semisynthetics (e.g., morphine and oxycodone), increased during 2010-2016,” they said.
It is possible that a change in mortality is lagging “behind changes in prescribing behaviors” or that “the trend in deaths related to these types of opioids has been driven by factors other than prescription opioid misuse rates, such as increasing mortality from heroin, which is frequently classified as morphine or found concomitantly with morphine postmortem, and a spike in deaths involving illicitly manufactured fentanyl combined with heroin and prescribed opioids since 2013,” the investigators suggested.
SOURCE: Strickler GK et al. MMWR Surveill Summ. 2020 Jan 31;69(1):1-14.
FROM MMWR SURVEILLANCE SUMMARIES
Rural treatment of opioid use disorder increasingly driven by nonphysician workforce
Nurse practitioners and physician assistants, rather than physicians, are the clinicians who have boosted capacity for buprenorphine prescribing in rural America, according to a study in a rural health–focused issue of the journal Health Affairs.
In the face of an ongoing crisis of opioid use disorder, and associated overdoses and deaths that have spared no sector of the U.S. population, the federal government expanded its waiver program for buprenorphine prescribing in 2017. The waiver expansion allows nurse practitioners (NPs) and physician assistants (PAs) – along with clinical nurse specialists, certified registered nurse anesthetists, and certified nurse-midwives – to use the drug for medication-assisted treatment (MAT) for opioid use disorder after completing 24 hours of mandated training; physicians are required to complete 8 hours of training to receive their waiver.
From 2016 to 2019, capacity for MAT in rural areas increased, with the number of clinicians with buprenorphine waivers more than doubling. Of the newly waivered prescribers accounting for this 111% increase, more than half were NPs and PAs.
In many areas, NPs and PAs led the way forward, wrote the study’s lead author Michael L. Barnett, MD, and coauthors, noting in the abstract accompanying the paper that “NPs and PAs accounted for more than half of this increase and were the first waivered clinicians in 285 rural counties with 5.7 million residents.” Overall, the proportion of people living in a county without a waivered clinician has decreased by 36% since NPs and PAs were permitted to obtain waivers.
SAMHSA data identifies trends
In an in-depth interview, Dr. Barnett, an internal medicine physician and health services researcher at the Harvard School of Public Health, Boston, said the issue today is “not so much continuing to dissect the risks and benefits of opioids as a treatment for pain, but more trying to address the current overdose crisis, and the fact that our patient treatment infrastructure is woefully inadequate for the magnitude of the problem that we face.”
Dr. Barnett’s chief intention for this study, he said, was to generate information that will drive policy to implement effective opioid treatment. He’d always been interested in models of care delivery that move beyond seeing just the physician-patient dyad.
“There are a whole range of nonphysician providers that are probably better at providing many different types of care – things that physicians aren’t necessarily that well trained to do,” he said.
Expansion of buprenorphine waivers to NPs and PAs, said Dr. Barnett, presented “a very interesting opportunity to see: How does a nonphysician workforce respond to a new practice opportunity, to really be engaged in areas that many physicians really were neglecting?”
The researchers used information drawn from what Dr. Barnett characterized as a “gold-standard” dataset maintained by the federal Substance Abuse and Mental Health Services Administration. They found that, by March 2019, 52% of U.S. rural residents lived in counties with at least one NP or PA holding a buprenorphine waiver, though there was wide geographic variation: Every county in Maine and New Hampshire had waivered NPs or PAs, but in Tennessee, just 3 of 95 counties had an NP or PA with a waiver.
Scope-of-practice regulations matter
The scope of practice permitted NPs and PAs varies by state, and Dr. Barnett and coauthors also looked to see whether broader scope of practice meant that more advanced practice clinicians were getting buprenorphine waivers. This did appear to be the case: In an analysis that dichotomized scope of practice into “broad” and “restricted,” states with broader practice scope saw twice as many waivered NPs per 100,000 rural residents as those with restrictive practice scope. This association was not seen for PAs, but Dr. Barnett pointed out that PAs are less likely overall to work in primary care.
This, he added, is where scope of practice starts to matter. “A lot of states are still bickering about scope of practice. We show in our paper the clear relationship between scope of practice and the degree to which providers are able to take up these waivers. We can’t prove causality, but I think it’s not a big stretch to think that these policies are playing a big role. I hope we’re working to try to advance that conversation.”
Helping address the unmet need for evidence-based treatment of opioid use disorder, he said, “is one of the more important examples, because doctors have been leaving rural areas in droves. We are lucky that there is a workforce of NPs that still seem to recognize the market opportunity; rural areas still need providers, and they have been willing to fill the gap.”
Waivered NPs or PAs can apply for an expanded waiver, permitting expansion of the buprenorphine panel from 30 to 100 patients after 1 year of holding their initial waiver. Physicians may apply for a waiver to treat up to 275 patients.
Effect on quality of care
The evidence doesn’t support big worries about quality of care, he said. “We don’t have any data on this in the clinical context of addiction, but all of the data that are out there in terms of evaluating the quality of care and level of care being offered by NPs and PAs versus primary care doctors – the types of things that we think of as within the scope of NP and PA practice typically – have shown that they are the same.” Dr. Barnett acknowledged that “there are a little bit of mixed results here and there in one direction or another, but largely, the care being delivered is much more the same than different.”
In addressing the opioid crisis as in the rest of medicine, it’s a mistake not to include this sector of the health care workforce when policies are being crafted, said Dr. Barnett. “People who are making policy and aren’t familiar with the workforce in rural areas could miss the boat. ... NPs aren’t just an asterisk to the workforce – they are an essential part of delivering medicine, just as much as physicians are.”
Dr. Barnett said that, in his estimation, “a lot of protectionist myths get physicians worked up around increased scope of practice for NPs.” However, “The truth is that there’s enough health care spending to go around for everybody and there’s plenty of work to go around.”
Dr. Barnett acknowledged that the current study captured only prescribing capacity, and not actual prescription volume. But, based on some preliminary data, “my sense is that NPs and PAs who acquire waivers are more likely to be prescribing to a larger number of patients proportionately than MDs.” He wasn’t surprised to see this, since the many more hours of training required for NPs and PAs to acquire a waiver means they’re likely to be committed to using the waiver in practice.
Stepping back to look at the bigger picture, Dr. Barnett remarked that, “taking a look at the waiver requirement, a part of me feels that it’s a bit of an anachronistic regulation, anyway – it’s really hard to justify clinically or ethically versus other things that we do.” The waiver program he said, is “a regulation barrier whose time should be limited. ... I’m hoping that the waiver disappears soon.”
Prescribing issues will linger beyond any future abolition of the waiver program, since many clinicians will still not be comfortable prescribing medication for MAT of opioid use disorder, said Dr. Barnett. “It’ll be a lot of the same stigma and structural barriers that were in place prior to the waiver.”
Dr. Barnett reported that he has been retained as an expert witness for plaintiffs in lawsuits against opioid manufacturers. The study was partly funded by the National Institutes of Health.
SOURCE: Barnett ML et al. Health Aff. 2019 Jan;38(12):2048-56.
Nurse practitioners and physician assistants, rather than physicians, are the clinicians who have boosted capacity for buprenorphine prescribing in rural America, according to a study in a rural health–focused issue of the journal Health Affairs.
In the face of an ongoing crisis of opioid use disorder, and associated overdoses and deaths that have spared no sector of the U.S. population, the federal government expanded its waiver program for buprenorphine prescribing in 2017. The waiver expansion allows nurse practitioners (NPs) and physician assistants (PAs) – along with clinical nurse specialists, certified registered nurse anesthetists, and certified nurse-midwives – to use the drug for medication-assisted treatment (MAT) for opioid use disorder after completing 24 hours of mandated training; physicians are required to complete 8 hours of training to receive their waiver.
From 2016 to 2019, capacity for MAT in rural areas increased, with the number of clinicians with buprenorphine waivers more than doubling. Of the newly waivered prescribers accounting for this 111% increase, more than half were NPs and PAs.
In many areas, NPs and PAs led the way forward, wrote the study’s lead author Michael L. Barnett, MD, and coauthors, noting in the abstract accompanying the paper that “NPs and PAs accounted for more than half of this increase and were the first waivered clinicians in 285 rural counties with 5.7 million residents.” Overall, the proportion of people living in a county without a waivered clinician has decreased by 36% since NPs and PAs were permitted to obtain waivers.
SAMHSA data identifies trends
In an in-depth interview, Dr. Barnett, an internal medicine physician and health services researcher at the Harvard School of Public Health, Boston, said the issue today is “not so much continuing to dissect the risks and benefits of opioids as a treatment for pain, but more trying to address the current overdose crisis, and the fact that our patient treatment infrastructure is woefully inadequate for the magnitude of the problem that we face.”
Dr. Barnett’s chief intention for this study, he said, was to generate information that will drive policy to implement effective opioid treatment. He’d always been interested in models of care delivery that move beyond seeing just the physician-patient dyad.
“There are a whole range of nonphysician providers that are probably better at providing many different types of care – things that physicians aren’t necessarily that well trained to do,” he said.
Expansion of buprenorphine waivers to NPs and PAs, said Dr. Barnett, presented “a very interesting opportunity to see: How does a nonphysician workforce respond to a new practice opportunity, to really be engaged in areas that many physicians really were neglecting?”
The researchers used information drawn from what Dr. Barnett characterized as a “gold-standard” dataset maintained by the federal Substance Abuse and Mental Health Services Administration. They found that, by March 2019, 52% of U.S. rural residents lived in counties with at least one NP or PA holding a buprenorphine waiver, though there was wide geographic variation: Every county in Maine and New Hampshire had waivered NPs or PAs, but in Tennessee, just 3 of 95 counties had an NP or PA with a waiver.
Scope-of-practice regulations matter
The scope of practice permitted NPs and PAs varies by state, and Dr. Barnett and coauthors also looked to see whether broader scope of practice meant that more advanced practice clinicians were getting buprenorphine waivers. This did appear to be the case: In an analysis that dichotomized scope of practice into “broad” and “restricted,” states with broader practice scope saw twice as many waivered NPs per 100,000 rural residents as those with restrictive practice scope. This association was not seen for PAs, but Dr. Barnett pointed out that PAs are less likely overall to work in primary care.
This, he added, is where scope of practice starts to matter. “A lot of states are still bickering about scope of practice. We show in our paper the clear relationship between scope of practice and the degree to which providers are able to take up these waivers. We can’t prove causality, but I think it’s not a big stretch to think that these policies are playing a big role. I hope we’re working to try to advance that conversation.”
Helping address the unmet need for evidence-based treatment of opioid use disorder, he said, “is one of the more important examples, because doctors have been leaving rural areas in droves. We are lucky that there is a workforce of NPs that still seem to recognize the market opportunity; rural areas still need providers, and they have been willing to fill the gap.”
Waivered NPs or PAs can apply for an expanded waiver, permitting expansion of the buprenorphine panel from 30 to 100 patients after 1 year of holding their initial waiver. Physicians may apply for a waiver to treat up to 275 patients.
Effect on quality of care
The evidence doesn’t support big worries about quality of care, he said. “We don’t have any data on this in the clinical context of addiction, but all of the data that are out there in terms of evaluating the quality of care and level of care being offered by NPs and PAs versus primary care doctors – the types of things that we think of as within the scope of NP and PA practice typically – have shown that they are the same.” Dr. Barnett acknowledged that “there are a little bit of mixed results here and there in one direction or another, but largely, the care being delivered is much more the same than different.”
In addressing the opioid crisis as in the rest of medicine, it’s a mistake not to include this sector of the health care workforce when policies are being crafted, said Dr. Barnett. “People who are making policy and aren’t familiar with the workforce in rural areas could miss the boat. ... NPs aren’t just an asterisk to the workforce – they are an essential part of delivering medicine, just as much as physicians are.”
Dr. Barnett said that, in his estimation, “a lot of protectionist myths get physicians worked up around increased scope of practice for NPs.” However, “The truth is that there’s enough health care spending to go around for everybody and there’s plenty of work to go around.”
Dr. Barnett acknowledged that the current study captured only prescribing capacity, and not actual prescription volume. But, based on some preliminary data, “my sense is that NPs and PAs who acquire waivers are more likely to be prescribing to a larger number of patients proportionately than MDs.” He wasn’t surprised to see this, since the many more hours of training required for NPs and PAs to acquire a waiver means they’re likely to be committed to using the waiver in practice.
Stepping back to look at the bigger picture, Dr. Barnett remarked that, “taking a look at the waiver requirement, a part of me feels that it’s a bit of an anachronistic regulation, anyway – it’s really hard to justify clinically or ethically versus other things that we do.” The waiver program he said, is “a regulation barrier whose time should be limited. ... I’m hoping that the waiver disappears soon.”
Prescribing issues will linger beyond any future abolition of the waiver program, since many clinicians will still not be comfortable prescribing medication for MAT of opioid use disorder, said Dr. Barnett. “It’ll be a lot of the same stigma and structural barriers that were in place prior to the waiver.”
Dr. Barnett reported that he has been retained as an expert witness for plaintiffs in lawsuits against opioid manufacturers. The study was partly funded by the National Institutes of Health.
SOURCE: Barnett ML et al. Health Aff. 2019 Jan;38(12):2048-56.
Nurse practitioners and physician assistants, rather than physicians, are the clinicians who have boosted capacity for buprenorphine prescribing in rural America, according to a study in a rural health–focused issue of the journal Health Affairs.
In the face of an ongoing crisis of opioid use disorder, and associated overdoses and deaths that have spared no sector of the U.S. population, the federal government expanded its waiver program for buprenorphine prescribing in 2017. The waiver expansion allows nurse practitioners (NPs) and physician assistants (PAs) – along with clinical nurse specialists, certified registered nurse anesthetists, and certified nurse-midwives – to use the drug for medication-assisted treatment (MAT) for opioid use disorder after completing 24 hours of mandated training; physicians are required to complete 8 hours of training to receive their waiver.
From 2016 to 2019, capacity for MAT in rural areas increased, with the number of clinicians with buprenorphine waivers more than doubling. Of the newly waivered prescribers accounting for this 111% increase, more than half were NPs and PAs.
In many areas, NPs and PAs led the way forward, wrote the study’s lead author Michael L. Barnett, MD, and coauthors, noting in the abstract accompanying the paper that “NPs and PAs accounted for more than half of this increase and were the first waivered clinicians in 285 rural counties with 5.7 million residents.” Overall, the proportion of people living in a county without a waivered clinician has decreased by 36% since NPs and PAs were permitted to obtain waivers.
SAMHSA data identifies trends
In an in-depth interview, Dr. Barnett, an internal medicine physician and health services researcher at the Harvard School of Public Health, Boston, said the issue today is “not so much continuing to dissect the risks and benefits of opioids as a treatment for pain, but more trying to address the current overdose crisis, and the fact that our patient treatment infrastructure is woefully inadequate for the magnitude of the problem that we face.”
Dr. Barnett’s chief intention for this study, he said, was to generate information that will drive policy to implement effective opioid treatment. He’d always been interested in models of care delivery that move beyond seeing just the physician-patient dyad.
“There are a whole range of nonphysician providers that are probably better at providing many different types of care – things that physicians aren’t necessarily that well trained to do,” he said.
Expansion of buprenorphine waivers to NPs and PAs, said Dr. Barnett, presented “a very interesting opportunity to see: How does a nonphysician workforce respond to a new practice opportunity, to really be engaged in areas that many physicians really were neglecting?”
The researchers used information drawn from what Dr. Barnett characterized as a “gold-standard” dataset maintained by the federal Substance Abuse and Mental Health Services Administration. They found that, by March 2019, 52% of U.S. rural residents lived in counties with at least one NP or PA holding a buprenorphine waiver, though there was wide geographic variation: Every county in Maine and New Hampshire had waivered NPs or PAs, but in Tennessee, just 3 of 95 counties had an NP or PA with a waiver.
Scope-of-practice regulations matter
The scope of practice permitted NPs and PAs varies by state, and Dr. Barnett and coauthors also looked to see whether broader scope of practice meant that more advanced practice clinicians were getting buprenorphine waivers. This did appear to be the case: In an analysis that dichotomized scope of practice into “broad” and “restricted,” states with broader practice scope saw twice as many waivered NPs per 100,000 rural residents as those with restrictive practice scope. This association was not seen for PAs, but Dr. Barnett pointed out that PAs are less likely overall to work in primary care.
This, he added, is where scope of practice starts to matter. “A lot of states are still bickering about scope of practice. We show in our paper the clear relationship between scope of practice and the degree to which providers are able to take up these waivers. We can’t prove causality, but I think it’s not a big stretch to think that these policies are playing a big role. I hope we’re working to try to advance that conversation.”
Helping address the unmet need for evidence-based treatment of opioid use disorder, he said, “is one of the more important examples, because doctors have been leaving rural areas in droves. We are lucky that there is a workforce of NPs that still seem to recognize the market opportunity; rural areas still need providers, and they have been willing to fill the gap.”
Waivered NPs or PAs can apply for an expanded waiver, permitting expansion of the buprenorphine panel from 30 to 100 patients after 1 year of holding their initial waiver. Physicians may apply for a waiver to treat up to 275 patients.
Effect on quality of care
The evidence doesn’t support big worries about quality of care, he said. “We don’t have any data on this in the clinical context of addiction, but all of the data that are out there in terms of evaluating the quality of care and level of care being offered by NPs and PAs versus primary care doctors – the types of things that we think of as within the scope of NP and PA practice typically – have shown that they are the same.” Dr. Barnett acknowledged that “there are a little bit of mixed results here and there in one direction or another, but largely, the care being delivered is much more the same than different.”
In addressing the opioid crisis as in the rest of medicine, it’s a mistake not to include this sector of the health care workforce when policies are being crafted, said Dr. Barnett. “People who are making policy and aren’t familiar with the workforce in rural areas could miss the boat. ... NPs aren’t just an asterisk to the workforce – they are an essential part of delivering medicine, just as much as physicians are.”
Dr. Barnett said that, in his estimation, “a lot of protectionist myths get physicians worked up around increased scope of practice for NPs.” However, “The truth is that there’s enough health care spending to go around for everybody and there’s plenty of work to go around.”
Dr. Barnett acknowledged that the current study captured only prescribing capacity, and not actual prescription volume. But, based on some preliminary data, “my sense is that NPs and PAs who acquire waivers are more likely to be prescribing to a larger number of patients proportionately than MDs.” He wasn’t surprised to see this, since the many more hours of training required for NPs and PAs to acquire a waiver means they’re likely to be committed to using the waiver in practice.
Stepping back to look at the bigger picture, Dr. Barnett remarked that, “taking a look at the waiver requirement, a part of me feels that it’s a bit of an anachronistic regulation, anyway – it’s really hard to justify clinically or ethically versus other things that we do.” The waiver program he said, is “a regulation barrier whose time should be limited. ... I’m hoping that the waiver disappears soon.”
Prescribing issues will linger beyond any future abolition of the waiver program, since many clinicians will still not be comfortable prescribing medication for MAT of opioid use disorder, said Dr. Barnett. “It’ll be a lot of the same stigma and structural barriers that were in place prior to the waiver.”
Dr. Barnett reported that he has been retained as an expert witness for plaintiffs in lawsuits against opioid manufacturers. The study was partly funded by the National Institutes of Health.
SOURCE: Barnett ML et al. Health Aff. 2019 Jan;38(12):2048-56.
FROM HEALTH AFFAIRS