Reducing COVID-19 opioid deaths

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Reducing COVID-19 opioid deaths

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

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

A crisis exacerbated by COVID-19 

The current drug overdose epidemic has become an American public health nightmare. According to preliminary data released by the CDC on December 17, 2020, there were more than 81,000 drug overdose deaths in the United States in the 12 months ending May 2020.2,3 This is the highest number of overdose deaths ever recorded in a 12-month period. The CDC also noted that while overdose deaths were already increasing in the months preceding the COVID-19 pandemic, the latest numbers suggest an acceleration of overdose deaths during the pandemic.

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

The increase in the number of opioid overdose deaths in part coincides with a sharp increase in the availability and use of heroin. Heroin overdose deaths have more than tripled since 2010, but heroin is not the only opiate involved. Fentanyl, a synthetic, short-acting opioid that is approved for managing pain in patients with advanced cancers, is 50 times more potent than heroin. The abuse of prescribed fentanyl has been accelerating over the past decade, as is the use of illicitly produced fentanyl. Evidence from US Drug Enforcement Administration (DEA) seizure records shows heroin is being adulterated with illicit fentanyl to enhance the potency of the heroin.6,7 Mixing illicit fentanyl with heroin may be contributing to the recent increase in heroin overdose fatalities. According to the CDC, overdose deaths related to synthetic opioids increased 38.4% from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020.2,3 Postmortem studies of individuals who died from a heroin overdose have frequently found the presence of fentanyl along with heroin.8 Overdose deaths involving heroin may be occurring because individuals may be unknowingly using heroin adulterated with fentanyl.9 In addition, carfentanil, a powerful new synthetic fentanyl, has been recently identified in heroin mixtures. Carfentanil is 10,000 times stronger than morphine. Even in miniscule amounts, carfentanil can suppress breathing to the degree that multiple doses of naloxone are needed to restore respirations.

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

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

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

Continue to: Strategies for intervention...

 

 

Strategies for intervention 

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

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

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

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

ASAM guidance for office-based opioid treatment during COVID-19

 
Expand access to treatment 
This includes access to MAT (such as buprenorphine/naloxone, methadone, naltrexone, and depot naltrexone) and, equally important, to psychosocial treatment, counseling, and/or recovery services. Recent legislative changes have increased the number of patients that a qualified physician can treat with buprenorphine/naloxone from 100 to 275, and allowed physician extenders to prescribe buprenorphine/naloxone in office-based settings. A recent population-based, retrospective Canadian study showed that opioid agonist treatment decreased the risk of mortality among opioid users, and the protective effects of this treatment increased as fentanyl and other synthetic opioids became common in the illicit drug supply.15 However, because of the shortage of psychiatrists and addiction medicine specialists in several regions of the United States, access to treatment is extremely limited and often inadequate. This constitutes a major public health crisis and contributes to our inability to intervene effectively in the opioid epidemic. Telepsychiatry programs can bring needed services to underserved areas, but they need additional support and development. Further, involving other specialties is paramount for treating this epidemic. Integrating MAT in primary care settings can improve access to treatment. Harm-reduction approaches, such as syringe exchange programs, can play an important role in reducing the adverse consequences associated with heroin use and establish health care relationships with at-risk individuals. Syringe exchange programs can also reduce the rate of infections associated with IV drug use, such as human immunodeficiency virus and hepatitis C virus.

Continue to: Increase education on naloxone...  

 

 

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

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

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

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

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

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

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

Bottom Line

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

References

1. Volkow ND. Collision of the COVID-19 and addiction epidemics. Ann Intern Med. 2020;173(1):61-62. 
2.Centers for Disease Control and Prevention. Overdose deaths accelerating during COVID-19. Accessed December 23, 2020. https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html
3.Centers for Disease Control and Prevention. National Center for Health Statistics Vital Statistics Rapid Release. Provisional drug overdose death counts. Accessed December 30, 2020. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
4.Rudd RA, Aleshire N, Zibbell JE, et al. Increases in drug and opioid overdose deaths -- United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016;64(50-51):1378-1382. 
5.Rudd RA, Seth P, David F, et al. Increases in drug and opioid-involved overdose deaths -- United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. 
6.US Drug Enforcement Administration. DEA issues nationwide alert on fentanyl as threat to health and public safety. Published March 19, 2015. Accessed October 28, 2020. http://www.dea.gov/divisions/hq/2015/hq031815.shtml  
7.Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions and increases in synthetic opioid-involved overdose deaths - 27 states, 2013-2014. MMWR Morb Mortal Wkly Rep. 2016;65(33):837-843. 
8.Algren DA, Monteilh CP, Punja M, et al. Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006). J Med Toxicol. 2013;9(1):106-115. 
9.Centers for Disease Control and Prevention. Increases in fentanyl drug confiscations and fentanyl-related overdose fatalities. HAN Health Advisory. Published October 26, 2015. Accessed October 28, 2020. http://emergency.cdc.gov/han/han00384.asp 
10.Wainwright JJ, Mikre M, Whitley P, et al. Analysis of drug test results before and after the us declaration of a national emergency concerning the COVID-19 outbreak. JAMA. 2020;324(16):1674-1677. 
11.Niles JK, Gudin J, Radliff J, et al. The opioid epidemic within the COVID-19 pandemic: drug testing in 2020 [published online October 8, 2020]. Population Health Management. doi: 10.1089/pop.2020.0230 
12.Ochalek TA, Cumpston KL, Wills BK, et al. Nonfatal opioid overdoses at an urban emergency department during the COVID-19 pandemic. JAMA. 2020;324(16):1673-1674. 
13.American Medical Association. Issue brief: reports of increases in opioid- and other drug-related overdose and other concerns during COVID pandemic. Published October 31, 2020. Accessed November 9, 2020. https://www.ama-assn.org/system/files/2020-11/issue-brief-increases-in-opioid-related-overdose.pdf 
14.American Society of Addiction Medicine. Caring for patients during the COVID-19 pandemic: ASAM COVID-19 Task Force recommendations. Accessed October 30, 2020. https://www.asam.org/docs/default-source/covid-19/medication-formulation-and-dosage-guidance-(1).pdf 
15.Pearce LA, Min JE, Piske M, et al. Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study. BMJ. 2020;368:m772. doi: 10.1136/bmj.m772 
16.North Carolina Harm Reduction Coalition. NCHRC'S community-based overdose prevention project. Accessed March 29, 2020. http://www.nchrc.org/programs-and-services 
17.Larochelle MR, Liebschutz JM, Zhang F, et al. Opioid prescribing after nonfatal overdose and association with repeated overdose: a cohort study. Ann Intern Med. 2016;164(1):1-9.

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Dr. Ashwin A. Patkar is an Adjunct Professor of Psychiatry, Rush University Medical Center Chicago, Illinois Chief, Avance Psychiatry Raleigh, North Carolina. Dr. John Beyer is a Professor of Psychiatry and Behavioral Sciences, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina. Dr. Ramez Ghanbari is a PGY-4 Psychiatry Resident, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina. Dr. Richard Weisler is an Adjunct Professor, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina, and Adjunct Professor, Department of Psychiatry, University of North Carolina at Chapel Hill Chapel Hill, North Carolina.

Disclosures
Dr. Patkar receives grant or research support from the National Institute on Drug Abuse, Substance Abuse and Mental Health Services Administration, National Institute on Alcohol Abuse and Alcoholism, Allergan, Envivo, and Sunovion. He is a consultant to Allergan, US World Meds, and Indivior. Dr. Patkar is a speaker for Janssen, Sage, and Otsuka. Dr. Weisler receives grant or research support from Allergan, Astellas, AxSome Therapeutics, Janssen, and Otsuka. He is a speaker for Allergan, Ironshore, Lundbeck, Neos Therapeutics, Otsuka, Shire, Supernus, Takeda, and Validus. Dr. Weisler is a consultant for Alkermes, Ironshore, Lundbeck, Major League Baseball, the National Football League, Neos Therapeutics, Otsuka, Shire, Supernus, Takeda, and Validus. Drs. Ghanbari and Beyer report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

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Dr. Ashwin A. Patkar is an Adjunct Professor of Psychiatry, Rush University Medical Center Chicago, Illinois Chief, Avance Psychiatry Raleigh, North Carolina. Dr. John Beyer is a Professor of Psychiatry and Behavioral Sciences, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina. Dr. Ramez Ghanbari is a PGY-4 Psychiatry Resident, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina. Dr. Richard Weisler is an Adjunct Professor, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina, and Adjunct Professor, Department of Psychiatry, University of North Carolina at Chapel Hill Chapel Hill, North Carolina.

Disclosures
Dr. Patkar receives grant or research support from the National Institute on Drug Abuse, Substance Abuse and Mental Health Services Administration, National Institute on Alcohol Abuse and Alcoholism, Allergan, Envivo, and Sunovion. He is a consultant to Allergan, US World Meds, and Indivior. Dr. Patkar is a speaker for Janssen, Sage, and Otsuka. Dr. Weisler receives grant or research support from Allergan, Astellas, AxSome Therapeutics, Janssen, and Otsuka. He is a speaker for Allergan, Ironshore, Lundbeck, Neos Therapeutics, Otsuka, Shire, Supernus, Takeda, and Validus. Dr. Weisler is a consultant for Alkermes, Ironshore, Lundbeck, Major League Baseball, the National Football League, Neos Therapeutics, Otsuka, Shire, Supernus, Takeda, and Validus. Drs. Ghanbari and Beyer report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Author and Disclosure Information

Dr. Ashwin A. Patkar is an Adjunct Professor of Psychiatry, Rush University Medical Center Chicago, Illinois Chief, Avance Psychiatry Raleigh, North Carolina. Dr. John Beyer is a Professor of Psychiatry and Behavioral Sciences, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina. Dr. Ramez Ghanbari is a PGY-4 Psychiatry Resident, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina. Dr. Richard Weisler is an Adjunct Professor, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine Durham, North Carolina, and Adjunct Professor, Department of Psychiatry, University of North Carolina at Chapel Hill Chapel Hill, North Carolina.

Disclosures
Dr. Patkar receives grant or research support from the National Institute on Drug Abuse, Substance Abuse and Mental Health Services Administration, National Institute on Alcohol Abuse and Alcoholism, Allergan, Envivo, and Sunovion. He is a consultant to Allergan, US World Meds, and Indivior. Dr. Patkar is a speaker for Janssen, Sage, and Otsuka. Dr. Weisler receives grant or research support from Allergan, Astellas, AxSome Therapeutics, Janssen, and Otsuka. He is a speaker for Allergan, Ironshore, Lundbeck, Neos Therapeutics, Otsuka, Shire, Supernus, Takeda, and Validus. Dr. Weisler is a consultant for Alkermes, Ironshore, Lundbeck, Major League Baseball, the National Football League, Neos Therapeutics, Otsuka, Shire, Supernus, Takeda, and Validus. Drs. Ghanbari and Beyer report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

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

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

A crisis exacerbated by COVID-19 

The current drug overdose epidemic has become an American public health nightmare. According to preliminary data released by the CDC on December 17, 2020, there were more than 81,000 drug overdose deaths in the United States in the 12 months ending May 2020.2,3 This is the highest number of overdose deaths ever recorded in a 12-month period. The CDC also noted that while overdose deaths were already increasing in the months preceding the COVID-19 pandemic, the latest numbers suggest an acceleration of overdose deaths during the pandemic.

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

The increase in the number of opioid overdose deaths in part coincides with a sharp increase in the availability and use of heroin. Heroin overdose deaths have more than tripled since 2010, but heroin is not the only opiate involved. Fentanyl, a synthetic, short-acting opioid that is approved for managing pain in patients with advanced cancers, is 50 times more potent than heroin. The abuse of prescribed fentanyl has been accelerating over the past decade, as is the use of illicitly produced fentanyl. Evidence from US Drug Enforcement Administration (DEA) seizure records shows heroin is being adulterated with illicit fentanyl to enhance the potency of the heroin.6,7 Mixing illicit fentanyl with heroin may be contributing to the recent increase in heroin overdose fatalities. According to the CDC, overdose deaths related to synthetic opioids increased 38.4% from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020.2,3 Postmortem studies of individuals who died from a heroin overdose have frequently found the presence of fentanyl along with heroin.8 Overdose deaths involving heroin may be occurring because individuals may be unknowingly using heroin adulterated with fentanyl.9 In addition, carfentanil, a powerful new synthetic fentanyl, has been recently identified in heroin mixtures. Carfentanil is 10,000 times stronger than morphine. Even in miniscule amounts, carfentanil can suppress breathing to the degree that multiple doses of naloxone are needed to restore respirations.

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

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

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

Continue to: Strategies for intervention...

 

 

Strategies for intervention 

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

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

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

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

ASAM guidance for office-based opioid treatment during COVID-19

 
Expand access to treatment 
This includes access to MAT (such as buprenorphine/naloxone, methadone, naltrexone, and depot naltrexone) and, equally important, to psychosocial treatment, counseling, and/or recovery services. Recent legislative changes have increased the number of patients that a qualified physician can treat with buprenorphine/naloxone from 100 to 275, and allowed physician extenders to prescribe buprenorphine/naloxone in office-based settings. A recent population-based, retrospective Canadian study showed that opioid agonist treatment decreased the risk of mortality among opioid users, and the protective effects of this treatment increased as fentanyl and other synthetic opioids became common in the illicit drug supply.15 However, because of the shortage of psychiatrists and addiction medicine specialists in several regions of the United States, access to treatment is extremely limited and often inadequate. This constitutes a major public health crisis and contributes to our inability to intervene effectively in the opioid epidemic. Telepsychiatry programs can bring needed services to underserved areas, but they need additional support and development. Further, involving other specialties is paramount for treating this epidemic. Integrating MAT in primary care settings can improve access to treatment. Harm-reduction approaches, such as syringe exchange programs, can play an important role in reducing the adverse consequences associated with heroin use and establish health care relationships with at-risk individuals. Syringe exchange programs can also reduce the rate of infections associated with IV drug use, such as human immunodeficiency virus and hepatitis C virus.

Continue to: Increase education on naloxone...  

 

 

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

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

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

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

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

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

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

Bottom Line

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

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

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

A crisis exacerbated by COVID-19 

The current drug overdose epidemic has become an American public health nightmare. According to preliminary data released by the CDC on December 17, 2020, there were more than 81,000 drug overdose deaths in the United States in the 12 months ending May 2020.2,3 This is the highest number of overdose deaths ever recorded in a 12-month period. The CDC also noted that while overdose deaths were already increasing in the months preceding the COVID-19 pandemic, the latest numbers suggest an acceleration of overdose deaths during the pandemic.

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

The increase in the number of opioid overdose deaths in part coincides with a sharp increase in the availability and use of heroin. Heroin overdose deaths have more than tripled since 2010, but heroin is not the only opiate involved. Fentanyl, a synthetic, short-acting opioid that is approved for managing pain in patients with advanced cancers, is 50 times more potent than heroin. The abuse of prescribed fentanyl has been accelerating over the past decade, as is the use of illicitly produced fentanyl. Evidence from US Drug Enforcement Administration (DEA) seizure records shows heroin is being adulterated with illicit fentanyl to enhance the potency of the heroin.6,7 Mixing illicit fentanyl with heroin may be contributing to the recent increase in heroin overdose fatalities. According to the CDC, overdose deaths related to synthetic opioids increased 38.4% from the 12-month period leading up to June 2019 compared with the 12-month period leading up to May 2020.2,3 Postmortem studies of individuals who died from a heroin overdose have frequently found the presence of fentanyl along with heroin.8 Overdose deaths involving heroin may be occurring because individuals may be unknowingly using heroin adulterated with fentanyl.9 In addition, carfentanil, a powerful new synthetic fentanyl, has been recently identified in heroin mixtures. Carfentanil is 10,000 times stronger than morphine. Even in miniscule amounts, carfentanil can suppress breathing to the degree that multiple doses of naloxone are needed to restore respirations.

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

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

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

Continue to: Strategies for intervention...

 

 

Strategies for intervention 

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

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

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

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

ASAM guidance for office-based opioid treatment during COVID-19

 
Expand access to treatment 
This includes access to MAT (such as buprenorphine/naloxone, methadone, naltrexone, and depot naltrexone) and, equally important, to psychosocial treatment, counseling, and/or recovery services. Recent legislative changes have increased the number of patients that a qualified physician can treat with buprenorphine/naloxone from 100 to 275, and allowed physician extenders to prescribe buprenorphine/naloxone in office-based settings. A recent population-based, retrospective Canadian study showed that opioid agonist treatment decreased the risk of mortality among opioid users, and the protective effects of this treatment increased as fentanyl and other synthetic opioids became common in the illicit drug supply.15 However, because of the shortage of psychiatrists and addiction medicine specialists in several regions of the United States, access to treatment is extremely limited and often inadequate. This constitutes a major public health crisis and contributes to our inability to intervene effectively in the opioid epidemic. Telepsychiatry programs can bring needed services to underserved areas, but they need additional support and development. Further, involving other specialties is paramount for treating this epidemic. Integrating MAT in primary care settings can improve access to treatment. Harm-reduction approaches, such as syringe exchange programs, can play an important role in reducing the adverse consequences associated with heroin use and establish health care relationships with at-risk individuals. Syringe exchange programs can also reduce the rate of infections associated with IV drug use, such as human immunodeficiency virus and hepatitis C virus.

Continue to: Increase education on naloxone...  

 

 

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

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

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

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

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

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

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

Bottom Line

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

References

1. Volkow ND. Collision of the COVID-19 and addiction epidemics. Ann Intern Med. 2020;173(1):61-62. 
2.Centers for Disease Control and Prevention. Overdose deaths accelerating during COVID-19. Accessed December 23, 2020. https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html
3.Centers for Disease Control and Prevention. National Center for Health Statistics Vital Statistics Rapid Release. Provisional drug overdose death counts. Accessed December 30, 2020. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
4.Rudd RA, Aleshire N, Zibbell JE, et al. Increases in drug and opioid overdose deaths -- United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016;64(50-51):1378-1382. 
5.Rudd RA, Seth P, David F, et al. Increases in drug and opioid-involved overdose deaths -- United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. 
6.US Drug Enforcement Administration. DEA issues nationwide alert on fentanyl as threat to health and public safety. Published March 19, 2015. Accessed October 28, 2020. http://www.dea.gov/divisions/hq/2015/hq031815.shtml  
7.Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions and increases in synthetic opioid-involved overdose deaths - 27 states, 2013-2014. MMWR Morb Mortal Wkly Rep. 2016;65(33):837-843. 
8.Algren DA, Monteilh CP, Punja M, et al. Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006). J Med Toxicol. 2013;9(1):106-115. 
9.Centers for Disease Control and Prevention. Increases in fentanyl drug confiscations and fentanyl-related overdose fatalities. HAN Health Advisory. Published October 26, 2015. Accessed October 28, 2020. http://emergency.cdc.gov/han/han00384.asp 
10.Wainwright JJ, Mikre M, Whitley P, et al. Analysis of drug test results before and after the us declaration of a national emergency concerning the COVID-19 outbreak. JAMA. 2020;324(16):1674-1677. 
11.Niles JK, Gudin J, Radliff J, et al. The opioid epidemic within the COVID-19 pandemic: drug testing in 2020 [published online October 8, 2020]. Population Health Management. doi: 10.1089/pop.2020.0230 
12.Ochalek TA, Cumpston KL, Wills BK, et al. Nonfatal opioid overdoses at an urban emergency department during the COVID-19 pandemic. JAMA. 2020;324(16):1673-1674. 
13.American Medical Association. Issue brief: reports of increases in opioid- and other drug-related overdose and other concerns during COVID pandemic. Published October 31, 2020. Accessed November 9, 2020. https://www.ama-assn.org/system/files/2020-11/issue-brief-increases-in-opioid-related-overdose.pdf 
14.American Society of Addiction Medicine. Caring for patients during the COVID-19 pandemic: ASAM COVID-19 Task Force recommendations. Accessed October 30, 2020. https://www.asam.org/docs/default-source/covid-19/medication-formulation-and-dosage-guidance-(1).pdf 
15.Pearce LA, Min JE, Piske M, et al. Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study. BMJ. 2020;368:m772. doi: 10.1136/bmj.m772 
16.North Carolina Harm Reduction Coalition. NCHRC'S community-based overdose prevention project. Accessed March 29, 2020. http://www.nchrc.org/programs-and-services 
17.Larochelle MR, Liebschutz JM, Zhang F, et al. Opioid prescribing after nonfatal overdose and association with repeated overdose: a cohort study. Ann Intern Med. 2016;164(1):1-9.

References

1. Volkow ND. Collision of the COVID-19 and addiction epidemics. Ann Intern Med. 2020;173(1):61-62. 
2.Centers for Disease Control and Prevention. Overdose deaths accelerating during COVID-19. Accessed December 23, 2020. https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html
3.Centers for Disease Control and Prevention. National Center for Health Statistics Vital Statistics Rapid Release. Provisional drug overdose death counts. Accessed December 30, 2020. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
4.Rudd RA, Aleshire N, Zibbell JE, et al. Increases in drug and opioid overdose deaths -- United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016;64(50-51):1378-1382. 
5.Rudd RA, Seth P, David F, et al. Increases in drug and opioid-involved overdose deaths -- United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. 
6.US Drug Enforcement Administration. DEA issues nationwide alert on fentanyl as threat to health and public safety. Published March 19, 2015. Accessed October 28, 2020. http://www.dea.gov/divisions/hq/2015/hq031815.shtml  
7.Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions and increases in synthetic opioid-involved overdose deaths - 27 states, 2013-2014. MMWR Morb Mortal Wkly Rep. 2016;65(33):837-843. 
8.Algren DA, Monteilh CP, Punja M, et al. Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006). J Med Toxicol. 2013;9(1):106-115. 
9.Centers for Disease Control and Prevention. Increases in fentanyl drug confiscations and fentanyl-related overdose fatalities. HAN Health Advisory. Published October 26, 2015. Accessed October 28, 2020. http://emergency.cdc.gov/han/han00384.asp 
10.Wainwright JJ, Mikre M, Whitley P, et al. Analysis of drug test results before and after the us declaration of a national emergency concerning the COVID-19 outbreak. JAMA. 2020;324(16):1674-1677. 
11.Niles JK, Gudin J, Radliff J, et al. The opioid epidemic within the COVID-19 pandemic: drug testing in 2020 [published online October 8, 2020]. Population Health Management. doi: 10.1089/pop.2020.0230 
12.Ochalek TA, Cumpston KL, Wills BK, et al. Nonfatal opioid overdoses at an urban emergency department during the COVID-19 pandemic. JAMA. 2020;324(16):1673-1674. 
13.American Medical Association. Issue brief: reports of increases in opioid- and other drug-related overdose and other concerns during COVID pandemic. Published October 31, 2020. Accessed November 9, 2020. https://www.ama-assn.org/system/files/2020-11/issue-brief-increases-in-opioid-related-overdose.pdf 
14.American Society of Addiction Medicine. Caring for patients during the COVID-19 pandemic: ASAM COVID-19 Task Force recommendations. Accessed October 30, 2020. https://www.asam.org/docs/default-source/covid-19/medication-formulation-and-dosage-guidance-(1).pdf 
15.Pearce LA, Min JE, Piske M, et al. Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study. BMJ. 2020;368:m772. doi: 10.1136/bmj.m772 
16.North Carolina Harm Reduction Coalition. NCHRC'S community-based overdose prevention project. Accessed March 29, 2020. http://www.nchrc.org/programs-and-services 
17.Larochelle MR, Liebschutz JM, Zhang F, et al. Opioid prescribing after nonfatal overdose and association with repeated overdose: a cohort study. Ann Intern Med. 2016;164(1):1-9.

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Dr. Patkar is Associate Professor of Psychiatry and Medical Director, Duke Addictions Program, Duke University Medical Center, Durham, North Carolina.

Dr. Weisler is Adjunct Associate Professor of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, and Adjunct Professor of Psychiatry, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina.

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Opioid abuse and overdose are large and growing problems, and in recent years the numbers have been staggering. Overdose deaths related to opioids increased from 28,647 in 2014 to 33,091 in 2015 (Figure).1 More than 2 million individuals in the United States had opioid use disorder in 2015,2 and approximately 80% of them received no treatment,3 even though effective treatment could reduce the scope of abuse.4,5

Although psychiatrists typically are not the primary prescribers of opioid medications, they often treat psychiatric disorders in patients with chronic pain who take prescription opioids. A recent study found that, despite representing only 16% of the adult population, adults with mental health disorders receive more than one-half of all opioid prescriptions distributed each year in the United States.6 Therefore, psychiatrists must be aware of risk assessment strategies for patients receiving opioids.

In this article, we provide recommendations for managing individuals with opioid use disorder, including:

  • how to identify risk factors for opioid use disorder and use screening tools
  • how to evaluate a patient with suspected opioid use disorder and make the diagnosis
  • how to treat a patient with opioid use disorder, including a review of approved pharmaceutical agents.

Risk factors for opioid abuse and overdose

Patients with a history of mental health and/or substance use disorders or at least 3 months of prescribed opioid treatment are at risk for opioid abuse. Those taking a high daily dose of opioids or who have a history of overdose are at risk for overdose from opioid abuse (Table 1).7-12 Standardized tools, such as the Opioid Risk Tool, can be used to screen to assess risk for opioid abuse among individuals prescribed opioids for treatment of chronic pain.12 However, clinicians must be aware that even patients without characteristic risk factors can become dependent on opioids and/or be at risk for an accidental or intentional overdose. For example, opioid therapy following surgical procedures, even in patients who do not have a history of opioid use, increases risk of developing opioid use disorder.13

Evaluation and diagnosis

DSM-5 criteria define 3 degrees of opioid use disorder, depending on how many of the following traits a patient exhibits (mild, 2 to 3; moderate, 4 to 5; and severe, ≥6 )14:

  • taking more than the initially intended quantities of opioids or for a longer period of time than intended
  • continuous attempts to reduce or otherwise manage opioid use or desires to do so
  • a great deal of time using, recovering from, or acquiring opioids
  • reports of strong cravings to use opioids
  • failing to meet personal objectives at home, work, or school
  • continued opioid use even though it causes recurrent social problems
  • reduction or elimination of activities the patient once considered important due to opioid use
  • opioid use in situations where it is physically dangerous
  • continued opioid use despite persistent psychological or physiologic problems despite knowing that continued use is causing or worsening those problems
  • tolerance to opioids (not consequential for the diagnosis if the patient is taking opioids under appropriate medical supervision)
  • withdrawal or use of opioids (or related substances) to prevent withdrawal (not consequential for the diagnosis if the patient is taking opioids under appropriate medical supervision).

Clinicians should be vigilant for symptoms of opioid use or withdrawal, such as needle marks and weight loss, during the interview (Table 2). High-risk populations that require regular screening include individuals with a history of opioid use disorder, patients taking chronic pain medication, and psychiatric patients.15 During the interview, clinicians should take an nonjudgmental approach and avoid “shame and blame.”


Patients often will withhold information about drug use for various reasons.16 Therefore, collateral information from the patient’s family, close friends, or a referral source is important.
 

Standardized scales. Various standardized scales can be used to evaluate patients for opioid withdrawal and risk for substance use disorder. Scales for assessing opioid withdrawal include:

  • Clinical Opiate Withdrawal Scale
  • Subjective Opiate Withdrawal Scale.

Substance use disorder screening tools include:

  • Drug Abuse Screen Test-10
  • Alcohol Use Disorders Identification Test
  • National Institute on Drug Abuse (NIDA) Drug Screening Tool.17

Examination findings. A brief physical examination is necessary to document key findings (Table 2). Patients should undergo a urine drug screen; gas chromatography/mass spectroscopy can confirm positive results. During the examination, clinicians should look for signs and symptoms of co-occurring substance use (eg, benzo­diazepines, marijuana, alcohol, cocaine) or mental disorders (mood, anxiety, attention-deficit).18-21 Because nonprescription opioid use is associated with increased risk of suicide attempts and ideation,22 a suicide risk assessment is necessary.

Managing opioid use disorder

Detoxification is a 3-tiered approach that requires judicious prescription of medication, psychosocial support, and supervision to relieve opioid withdrawal symptoms. In both inpatient and outpatient settings, medications used for opioid detoxification include buprenorphine, clonidine, and methadone administered in doses tapered over 5 to 7 days. Appropriate detoxification increases treatment retention for continuing care.23,24

Buprenorphine or buprenorphine/naloxone is the first-line option for outpatient and inpatient detoxification. Short-term detoxification schedules include starting doses between 4 and 16 mg/d, tapered over 5 to 7 days. Compared with methadone, buprenorphine has a lower risk of overdose25 and abuse potential and can be given in an office-based setting. Clonidine, 0.3 to 1.2 mg/d in divided doses, is an alternative to buprenorphine and can be used in in­patient settings.26

Clonidine is not as effective as buprenorphine for detoxification, but it may be used when buprenorphine is contraindicated. Clonidine may require adjuvant symptomatic treatment for insomnia (eg, trazodone, 100 mg at bedtime), anxiety (eg, hydroxyzine, 25 mg, twice a day), or diarrhea (loperamide, 2 mg/d). If a patient needs more structure and monitoring, he (she) should be referred for inpatient detoxification or to a methadone program.27

 

 

 

Medication-assisted therapies

Detoxification alone often is not sufficient treatment. Medication-assisted therapy (MAT) is typically recommended by federal guidelines provided by the Substance Abuse and Mental Health Administration (SAMHSA) for patients with opioid use disorders.3 Patients can be directly transitioned from currently abused opioids to MAT on an outpatient basis. FDA-approved medications for MAT for opioid use disorder include buprenorphine, naltrexone (oral and long-acting injectable), and methadone (Table 3). Choice of MAT depends on several factors, including cost, patient preference, and availability of methadone programs and buprenorphine providers.28

MAT should include psychosocial support29-33 and active monitoring with urine drug screens. Maintenance therapy with medications is usually long-term and has been shown to have better outcomes than detoxification alone or short-term treatment.34 Relapse during MAT should not be cause to discontinue treatment; instead, the patient should be referred to a higher level of care.

Some patients require individualized treatment approaches. For example, the SAMHSA has developed specific treatment improvement protocols to tailor treatments to address specific needs of adolescents.32 The American Academy of Pediatrics recommends MAT with buprenorphine in adolescents with opioid use disorder.33 Although methadone has been approved for pregnant, opioid-dependent patients, recent data indicate buprenorphine is as effective with lower intensity of neonatal abstinence syndrome.34

Buprenorphine. This long-acting (half-life of 24 to 42 hours) opioid partial agonist is approved for treating opioid use disorder in office-based settings according to the Drug Abuse Treatment Act of 2000. Buprenorphine is administered in doses of 8 to 16 mg/d in film or tablet form (sublingual or buccal) and is available in various formulations (Table 4). It is well tolerated; constipation and unpleasant taste are the most common adverse effects. Physicians are required to have a federal waiver to obtain the Drug Enforcement Administration license to prescribe buprenorphine for opioid use disorder in an office setting.

Buprenorphine reduces or eliminates cravings and withdrawal symptoms and helps improve outcomes of abstinence from opioids and retention in treatment.31 Formulations of naloxone combined with buprenorphine reduce the risk of abuse via injection.35 Buprenorphine is safe; however, overdoses can occur when it is combined with benzodiazepines and/or other opiates.

Methadone. This long-acting (half-life 8 to 59 hours), full opioid agonist is approved to treat opioid addiction in federal- and state-regulated opioid treatment programs, also known as methadone maintenance programs. These programs are highly structured and include intensive counseling, monitoring, and dispensing to reduce relapse. Methadone is administered orally either via powder, liquid concentrate, tablet, or solution of diskette. Typically, methadone is dispensed daily in doses of 60 to 100 mg, although higher doses are sometimes necessary. Patients who meet certain criteria for stability may be allowed to take home supplies of methadone.

Methadone has a “black-box” warning for overdose, QT prolongation, and risk for respiratory depression when used in combination with benzodiazepines. Because of its long and unpredictable half-life and tissue accumulation, methadone carries a high overdose risk, particularly with rapidly titrated doses during therapy initiation.35 However, most overdose deaths have occurred with methadone prescribed for pain management. When prescribed and monitored in an opioid treatment program, methadone has shown a high safety profile with respect to overdoses.36

Injectable and oral naltrexone. Used for prevention of relapse to opioid dependence, naltrexone is a pure opioid antagonist that is available as an oral or IM form. Naltrexone has high affinity for the opioid receptors and in therapeutic doses provides an effective blockade for heroin or opioids. Compliance with oral naltrexone has been poor, leading to development of an IM form of naltrexone that can be administered as a single 380-mg dose once every 4 weeks for 6 months or sometimes longer. Naltrexone is also approved for alcohol dependence.

To avoid precipitated withdrawal, patients should be detoxified from opioids for 7 to 10 days before they begin naltrexone, which has no potential for abuse. Common adverse effects include fatigue, nausea, headache, and, for the IM formulation, injection site reactions. There is a “black-box” warning for liver toxicity; therefore, baseline and periodic liver function tests are necessary.

A NIDA review reported poor compliance with oral naltrexone compared with methadone.35 However, naltrexone has been shown to be effective in highly motivated patients (eg, impaired physicians) and the criminal justice population and for preventing relapse following taper from buprenorphine or methadone.37,38

Treatment for opioid overdose

Naloxone is a highly effective treatment to reverse opioid overdose that is delivered via IM or IV injection or by nasal application. Naloxone has no abuse potential. In doses of 0.4 to 2 mg, naloxone reverses overdose within 2 minutes and is effective for 30 to 90 minutes.39 One should call 911 as soon as possible after naloxone is administered. In several states, naloxone is available without a prescription for patients and family members to combat opioid overdoses. The CDC recommends offering naloxone to patients who have risk factors for opioid overdose.40

Bottom Line

The epidemic of opioid abuse and overdose has emphasized the importance of recognition and treatment of opioid use disorder. Buprenorphine/naloxone, methadone, and naltrexone formulations are approved treatments for opioid use disorder. Naloxone formulations are approved to treat opioid overdoses. Effective medication-assisted treatment should be long-term and include behavioral interventions and psychosocial support.

Related Resources

  • Rudd RA, Seth P, David F, et al. Increases in drug and opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(5051):1445-1452.
  • Nielsen S, Larance B, Degenhardt L, et al. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016;(5):CD011117. doi: 10.1002/14651858.CD011117.pub2.
  • Timko C, Schultz NR, Cucciare MA, et al. Retention in medication-assisted treatment for opiate dependence: a systematic review. J Addict Dis. 2016;35(1):22-35.

Drug Brand Names

Buprenorphine/naloxone • Suboxone, Subutex
Methadone • Dolophine
Naltrexone • Revia, Vivitrol
Naloxone • Narcan, Evzio

References

1. Centers for Disease Control and Prevention. Opioid data analysis. http://www.cdc.gov/drugoverdose/data/analysis.html. Updated February 9, 2017. Accessed June 27, 2017.
2. Substance Abuse and Mental Health Services Administration. Results from the 2015 National Survey on Drug Use and Health: detailed tables. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.pdf.
3. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment of opioid use disorder pocket guide. https://store.samhsa.gov/shin/content//SMA16-4892PG/SMA16-4892PG.pdf. Accessed June 29, 2017.
4. Mutlu C, Demirci AC, Yalcin O, et al. One-year follow-up of heroin-dependent adolescents treated with buprenorphine/naloxone for the first time in a substance treatment unit. J Subst Abuse Treat. 2016;67:1-8.
5. Sharma B, Bruner A, Barnett G, et al. Opioid use disorders. Child Adolesc Psychiatr Clin N Am. 2016;25(3):473-487.
6. Davis MA, Lin LA, Liu H, Sites BD. Prescription Opioid Use among Adults with mental health disorders in the United States. J Am Board Fam Med. 2017;30:42-47.
7. Icahn School of Medicine at Mount Sinai. Substance use: prescription drugs. http://www.mountsinai.org/patient-care/health-library/diseases-and-conditions/opioid-abuse#risk. Accessed June 27, 2017.
8. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction. 2010;105(10):1776-1782.
9. Edlund M, Steffick D, Hudson T, et al. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007;129(3):355-362.
10. Compton WM, Volkow ND. Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug Alcohol Depend. 2006;81(2):103-107.
11. Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315-1321.
12. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):432.
13. Sun EC, Darnall BD, Baker LC, et al. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med. 2016;176(9):1286-1293.
14. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
15. Starrels JL, Becker WC, Alford DP, et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Internal Med. 2010;152(11):712-720.
16. Substance Abuse and Mental Health Services Administration. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction: a treatment improvement protocol: TIP 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004.
17. NIDA drug screening tool: clinician’s screening tool for drug use in general medical settings. National Institutes of Health. https://www.drugabuse.gov/nmassist. Accessed June 27, 2017.
18. Fareed A, Eilender P, Haber M, et al. Comorbid posttraumatic stress disorder and opiate addiction: a literature review. J Addict Dis. 2013;32(2):168-179.
19. Rosen D, Smith ML, Reynolds CF 3rd. The prevalence of mental and physical health disorders among older methadone patients. Am J Geriatr Psychiatry. 2008;16(6):488-497.
20. Goldner EM, Lusted A, Roerecke M, et al. Prevalence of Axis-1 psychiatric (with focus on depression and anxiety) disorder and symptomatology among non-medical prescription opioid users in substance use treatment: systematic review and meta-analyses. Addict Behav. 2014;39(3):520-531.
21. Barry DT, Cutter CJ, Beitel M, et al. Psychiatric disorders among patients seeking treatment for co-occurring chronic pain and opioid use disorder. J Clin Psychiatry. 2016;77(10):1413-1419.
22. Kuramoto SJ, Chilcoat HD, Ko J, et al. Suicidal ideation and suicide attempt across stages of nonmedical prescription opioid use and presence of prescription opioid disorders among U.S. adults. J Stud Alcohol Drugs. 2012;73(2):178-184.
23. Mattick RP, Breen C, Kimber J, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;(2):CD002207. doi: 10.1002/14651858.CD002207.pub4.
24. Evans E, Li L, Min J, et al. Mortality among individuals accessing pharmacological treatment for opioid dependence in California, 2006-10. Addiction. 2015;110(6):996-1005.
25. Marteu D, McDonald R, Patel K. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales. BMJ Open. 2015;5(5):e007629. doi: 10.1136/bmjopen-2015-007629.
26. Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal. Differential effects on signs and symptoms. Arch Gen Psychiatry. 1985;42(11):1063-1066.
27. Whelan PJ, Remski K. Buprenorphine vs methadone treatment: a review of evidence in both developed and developing worlds. J Neurosci Rural Pract. 2012;3(1):45-50.
28. Schuckit MA. Treatment of opioid-use disorders. N Engl J Med. 2016;375(4):357-368.
29. Dutra L, Stathopoulou G, Basden SL, et al. A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry. 2008;165(2):179-187.
30. Brown HL, Britton KA, Mahaffey D, et al. Methadone maintenance in pregnancy: a reappraisal. Am J Obstet Gynecol. 1998;179(2):459-463.
31. Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) 43. HHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2005.
32. Zimlich R. AAP recommends on medication assisted therapy for adolescent opioid addiction. Contemporary Pediatrics. http://contemporarypediatrics.modernmedicine.com/contemporary-pediatrics/news/aap-recommends-medication-assisted-therapy-adolescent-opioid-addiction. Published September 15, 2016. Accessed June 29, 2017.
33. Patkar A, Lee J, Burgess D. Opioid use disorder. BMJ Publishing Group. http://bestpractice.bmj.com/best-practice/monograph/200.html. Published 2015. Accessed July 6, 2017.
34. Alho H, Sinclair D, Vuori E, et al. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend. 2007;88(1):75-78.
35. Centers for Disease Control and Prevention (CDC). Vital signs: risk for overdose from methadone used for pain relief - United States, 1999-2010. MMWR Morb Mortal Wkly Rep. 2012;61(26):493-497.
36. Soyka M. New developments in the management of opioid dependence: focus on sublingual buprenorphine-naloxone. Subst Abuse Rehabil. 2015;6:1-14.
37. Lee JD, Friedmann PD, Kinlock TW, et al. Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders N Engl J Med. 2016;374(13):1232-1242.
38. Vo HT, Robbins E, Westwood M, et al. Relapse prevention medications in community treatment for young adults with opioid addiction. Subst Abus. 2016;37(3):392-397.
39. McDonald R, Campbell ND, Strang J. Twenty years of take-home naloxone for the prevention of overdose deaths from heroin and other opioids-conception and maturation. Drug Alcohol Depend. 2017;178:176-187.
40. Centers for Disease Control and Prevention. Overdose prevention. https://www.cdc.gov/drugoverdose/opioids/odprevention.html. Updated February 9, 2017. Accessed July 6, 2017.

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Ashwin A. Patkar, MD
Department of Psychiatry
Duke University Medical Center
Durham, North Carolina

Richard H. Weisler, MD
Department of Psychiatry
Duke University Medical Center
Durham, North Carolina
Department of Psychiatry
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina

Disclosures
Dr. Patkar provides consulting and/or advisory board services for BioDelivery Sciences International and Radeas; is on the speaker’s bureau of BioDelivery Sciences International; has received grant support from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, Substance Abuse and Mental Health Services Administration, Daiichi Sankyo, EnVivo Pharmaceuticals, Allergan, and Sunovion Pharmaceuticals; and is a shareholder of Generys Biopharmaceuticals. Dr. Weisler has been a consultant to, Alcobra, Allergan, AltheaDx, Sunovion, Superus, Shire, Ironshore, Validus, Lundbeck, MLB, NFL, Neos Therapeutics, Nestle Health Sciences-Pam Labs, and Otsuka Pharmaceuticals; served on Speakers Bureau for Rhodes Pharmaceuticals, Shire, Sunovion, Validus, Lundbeck, Neos Therapeutics, Nestle Health Sciences-Pam Labs, and Otsuka Pharmaceuticals; and received research support from Alcobra, Roche, Allergan, Shire, Daiichi Sankyo, Genomind, Theravance, Johnson and Johnson, Merck, Neurim, and Otsuka Pharmaceuticals.

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August 2017
Publications
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Author and Disclosure Information

Ashwin A. Patkar, MD
Department of Psychiatry
Duke University Medical Center
Durham, North Carolina

Richard H. Weisler, MD
Department of Psychiatry
Duke University Medical Center
Durham, North Carolina
Department of Psychiatry
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina

Disclosures
Dr. Patkar provides consulting and/or advisory board services for BioDelivery Sciences International and Radeas; is on the speaker’s bureau of BioDelivery Sciences International; has received grant support from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, Substance Abuse and Mental Health Services Administration, Daiichi Sankyo, EnVivo Pharmaceuticals, Allergan, and Sunovion Pharmaceuticals; and is a shareholder of Generys Biopharmaceuticals. Dr. Weisler has been a consultant to, Alcobra, Allergan, AltheaDx, Sunovion, Superus, Shire, Ironshore, Validus, Lundbeck, MLB, NFL, Neos Therapeutics, Nestle Health Sciences-Pam Labs, and Otsuka Pharmaceuticals; served on Speakers Bureau for Rhodes Pharmaceuticals, Shire, Sunovion, Validus, Lundbeck, Neos Therapeutics, Nestle Health Sciences-Pam Labs, and Otsuka Pharmaceuticals; and received research support from Alcobra, Roche, Allergan, Shire, Daiichi Sankyo, Genomind, Theravance, Johnson and Johnson, Merck, Neurim, and Otsuka Pharmaceuticals.

Author and Disclosure Information

Ashwin A. Patkar, MD
Department of Psychiatry
Duke University Medical Center
Durham, North Carolina

Richard H. Weisler, MD
Department of Psychiatry
Duke University Medical Center
Durham, North Carolina
Department of Psychiatry
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina

Disclosures
Dr. Patkar provides consulting and/or advisory board services for BioDelivery Sciences International and Radeas; is on the speaker’s bureau of BioDelivery Sciences International; has received grant support from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, Substance Abuse and Mental Health Services Administration, Daiichi Sankyo, EnVivo Pharmaceuticals, Allergan, and Sunovion Pharmaceuticals; and is a shareholder of Generys Biopharmaceuticals. Dr. Weisler has been a consultant to, Alcobra, Allergan, AltheaDx, Sunovion, Superus, Shire, Ironshore, Validus, Lundbeck, MLB, NFL, Neos Therapeutics, Nestle Health Sciences-Pam Labs, and Otsuka Pharmaceuticals; served on Speakers Bureau for Rhodes Pharmaceuticals, Shire, Sunovion, Validus, Lundbeck, Neos Therapeutics, Nestle Health Sciences-Pam Labs, and Otsuka Pharmaceuticals; and received research support from Alcobra, Roche, Allergan, Shire, Daiichi Sankyo, Genomind, Theravance, Johnson and Johnson, Merck, Neurim, and Otsuka Pharmaceuticals.

Article PDF
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Opioid abuse and overdose are large and growing problems, and in recent years the numbers have been staggering. Overdose deaths related to opioids increased from 28,647 in 2014 to 33,091 in 2015 (Figure).1 More than 2 million individuals in the United States had opioid use disorder in 2015,2 and approximately 80% of them received no treatment,3 even though effective treatment could reduce the scope of abuse.4,5

Although psychiatrists typically are not the primary prescribers of opioid medications, they often treat psychiatric disorders in patients with chronic pain who take prescription opioids. A recent study found that, despite representing only 16% of the adult population, adults with mental health disorders receive more than one-half of all opioid prescriptions distributed each year in the United States.6 Therefore, psychiatrists must be aware of risk assessment strategies for patients receiving opioids.

In this article, we provide recommendations for managing individuals with opioid use disorder, including:

  • how to identify risk factors for opioid use disorder and use screening tools
  • how to evaluate a patient with suspected opioid use disorder and make the diagnosis
  • how to treat a patient with opioid use disorder, including a review of approved pharmaceutical agents.

Risk factors for opioid abuse and overdose

Patients with a history of mental health and/or substance use disorders or at least 3 months of prescribed opioid treatment are at risk for opioid abuse. Those taking a high daily dose of opioids or who have a history of overdose are at risk for overdose from opioid abuse (Table 1).7-12 Standardized tools, such as the Opioid Risk Tool, can be used to screen to assess risk for opioid abuse among individuals prescribed opioids for treatment of chronic pain.12 However, clinicians must be aware that even patients without characteristic risk factors can become dependent on opioids and/or be at risk for an accidental or intentional overdose. For example, opioid therapy following surgical procedures, even in patients who do not have a history of opioid use, increases risk of developing opioid use disorder.13

Evaluation and diagnosis

DSM-5 criteria define 3 degrees of opioid use disorder, depending on how many of the following traits a patient exhibits (mild, 2 to 3; moderate, 4 to 5; and severe, ≥6 )14:

  • taking more than the initially intended quantities of opioids or for a longer period of time than intended
  • continuous attempts to reduce or otherwise manage opioid use or desires to do so
  • a great deal of time using, recovering from, or acquiring opioids
  • reports of strong cravings to use opioids
  • failing to meet personal objectives at home, work, or school
  • continued opioid use even though it causes recurrent social problems
  • reduction or elimination of activities the patient once considered important due to opioid use
  • opioid use in situations where it is physically dangerous
  • continued opioid use despite persistent psychological or physiologic problems despite knowing that continued use is causing or worsening those problems
  • tolerance to opioids (not consequential for the diagnosis if the patient is taking opioids under appropriate medical supervision)
  • withdrawal or use of opioids (or related substances) to prevent withdrawal (not consequential for the diagnosis if the patient is taking opioids under appropriate medical supervision).

Clinicians should be vigilant for symptoms of opioid use or withdrawal, such as needle marks and weight loss, during the interview (Table 2). High-risk populations that require regular screening include individuals with a history of opioid use disorder, patients taking chronic pain medication, and psychiatric patients.15 During the interview, clinicians should take an nonjudgmental approach and avoid “shame and blame.”


Patients often will withhold information about drug use for various reasons.16 Therefore, collateral information from the patient’s family, close friends, or a referral source is important.
 

Standardized scales. Various standardized scales can be used to evaluate patients for opioid withdrawal and risk for substance use disorder. Scales for assessing opioid withdrawal include:

  • Clinical Opiate Withdrawal Scale
  • Subjective Opiate Withdrawal Scale.

Substance use disorder screening tools include:

  • Drug Abuse Screen Test-10
  • Alcohol Use Disorders Identification Test
  • National Institute on Drug Abuse (NIDA) Drug Screening Tool.17

Examination findings. A brief physical examination is necessary to document key findings (Table 2). Patients should undergo a urine drug screen; gas chromatography/mass spectroscopy can confirm positive results. During the examination, clinicians should look for signs and symptoms of co-occurring substance use (eg, benzo­diazepines, marijuana, alcohol, cocaine) or mental disorders (mood, anxiety, attention-deficit).18-21 Because nonprescription opioid use is associated with increased risk of suicide attempts and ideation,22 a suicide risk assessment is necessary.

Managing opioid use disorder

Detoxification is a 3-tiered approach that requires judicious prescription of medication, psychosocial support, and supervision to relieve opioid withdrawal symptoms. In both inpatient and outpatient settings, medications used for opioid detoxification include buprenorphine, clonidine, and methadone administered in doses tapered over 5 to 7 days. Appropriate detoxification increases treatment retention for continuing care.23,24

Buprenorphine or buprenorphine/naloxone is the first-line option for outpatient and inpatient detoxification. Short-term detoxification schedules include starting doses between 4 and 16 mg/d, tapered over 5 to 7 days. Compared with methadone, buprenorphine has a lower risk of overdose25 and abuse potential and can be given in an office-based setting. Clonidine, 0.3 to 1.2 mg/d in divided doses, is an alternative to buprenorphine and can be used in in­patient settings.26

Clonidine is not as effective as buprenorphine for detoxification, but it may be used when buprenorphine is contraindicated. Clonidine may require adjuvant symptomatic treatment for insomnia (eg, trazodone, 100 mg at bedtime), anxiety (eg, hydroxyzine, 25 mg, twice a day), or diarrhea (loperamide, 2 mg/d). If a patient needs more structure and monitoring, he (she) should be referred for inpatient detoxification or to a methadone program.27

 

 

 

Medication-assisted therapies

Detoxification alone often is not sufficient treatment. Medication-assisted therapy (MAT) is typically recommended by federal guidelines provided by the Substance Abuse and Mental Health Administration (SAMHSA) for patients with opioid use disorders.3 Patients can be directly transitioned from currently abused opioids to MAT on an outpatient basis. FDA-approved medications for MAT for opioid use disorder include buprenorphine, naltrexone (oral and long-acting injectable), and methadone (Table 3). Choice of MAT depends on several factors, including cost, patient preference, and availability of methadone programs and buprenorphine providers.28

MAT should include psychosocial support29-33 and active monitoring with urine drug screens. Maintenance therapy with medications is usually long-term and has been shown to have better outcomes than detoxification alone or short-term treatment.34 Relapse during MAT should not be cause to discontinue treatment; instead, the patient should be referred to a higher level of care.

Some patients require individualized treatment approaches. For example, the SAMHSA has developed specific treatment improvement protocols to tailor treatments to address specific needs of adolescents.32 The American Academy of Pediatrics recommends MAT with buprenorphine in adolescents with opioid use disorder.33 Although methadone has been approved for pregnant, opioid-dependent patients, recent data indicate buprenorphine is as effective with lower intensity of neonatal abstinence syndrome.34

Buprenorphine. This long-acting (half-life of 24 to 42 hours) opioid partial agonist is approved for treating opioid use disorder in office-based settings according to the Drug Abuse Treatment Act of 2000. Buprenorphine is administered in doses of 8 to 16 mg/d in film or tablet form (sublingual or buccal) and is available in various formulations (Table 4). It is well tolerated; constipation and unpleasant taste are the most common adverse effects. Physicians are required to have a federal waiver to obtain the Drug Enforcement Administration license to prescribe buprenorphine for opioid use disorder in an office setting.

Buprenorphine reduces or eliminates cravings and withdrawal symptoms and helps improve outcomes of abstinence from opioids and retention in treatment.31 Formulations of naloxone combined with buprenorphine reduce the risk of abuse via injection.35 Buprenorphine is safe; however, overdoses can occur when it is combined with benzodiazepines and/or other opiates.

Methadone. This long-acting (half-life 8 to 59 hours), full opioid agonist is approved to treat opioid addiction in federal- and state-regulated opioid treatment programs, also known as methadone maintenance programs. These programs are highly structured and include intensive counseling, monitoring, and dispensing to reduce relapse. Methadone is administered orally either via powder, liquid concentrate, tablet, or solution of diskette. Typically, methadone is dispensed daily in doses of 60 to 100 mg, although higher doses are sometimes necessary. Patients who meet certain criteria for stability may be allowed to take home supplies of methadone.

Methadone has a “black-box” warning for overdose, QT prolongation, and risk for respiratory depression when used in combination with benzodiazepines. Because of its long and unpredictable half-life and tissue accumulation, methadone carries a high overdose risk, particularly with rapidly titrated doses during therapy initiation.35 However, most overdose deaths have occurred with methadone prescribed for pain management. When prescribed and monitored in an opioid treatment program, methadone has shown a high safety profile with respect to overdoses.36

Injectable and oral naltrexone. Used for prevention of relapse to opioid dependence, naltrexone is a pure opioid antagonist that is available as an oral or IM form. Naltrexone has high affinity for the opioid receptors and in therapeutic doses provides an effective blockade for heroin or opioids. Compliance with oral naltrexone has been poor, leading to development of an IM form of naltrexone that can be administered as a single 380-mg dose once every 4 weeks for 6 months or sometimes longer. Naltrexone is also approved for alcohol dependence.

To avoid precipitated withdrawal, patients should be detoxified from opioids for 7 to 10 days before they begin naltrexone, which has no potential for abuse. Common adverse effects include fatigue, nausea, headache, and, for the IM formulation, injection site reactions. There is a “black-box” warning for liver toxicity; therefore, baseline and periodic liver function tests are necessary.

A NIDA review reported poor compliance with oral naltrexone compared with methadone.35 However, naltrexone has been shown to be effective in highly motivated patients (eg, impaired physicians) and the criminal justice population and for preventing relapse following taper from buprenorphine or methadone.37,38

Treatment for opioid overdose

Naloxone is a highly effective treatment to reverse opioid overdose that is delivered via IM or IV injection or by nasal application. Naloxone has no abuse potential. In doses of 0.4 to 2 mg, naloxone reverses overdose within 2 minutes and is effective for 30 to 90 minutes.39 One should call 911 as soon as possible after naloxone is administered. In several states, naloxone is available without a prescription for patients and family members to combat opioid overdoses. The CDC recommends offering naloxone to patients who have risk factors for opioid overdose.40

Bottom Line

The epidemic of opioid abuse and overdose has emphasized the importance of recognition and treatment of opioid use disorder. Buprenorphine/naloxone, methadone, and naltrexone formulations are approved treatments for opioid use disorder. Naloxone formulations are approved to treat opioid overdoses. Effective medication-assisted treatment should be long-term and include behavioral interventions and psychosocial support.

Related Resources

  • Rudd RA, Seth P, David F, et al. Increases in drug and opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(5051):1445-1452.
  • Nielsen S, Larance B, Degenhardt L, et al. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016;(5):CD011117. doi: 10.1002/14651858.CD011117.pub2.
  • Timko C, Schultz NR, Cucciare MA, et al. Retention in medication-assisted treatment for opiate dependence: a systematic review. J Addict Dis. 2016;35(1):22-35.

Drug Brand Names

Buprenorphine/naloxone • Suboxone, Subutex
Methadone • Dolophine
Naltrexone • Revia, Vivitrol
Naloxone • Narcan, Evzio

 

Opioid abuse and overdose are large and growing problems, and in recent years the numbers have been staggering. Overdose deaths related to opioids increased from 28,647 in 2014 to 33,091 in 2015 (Figure).1 More than 2 million individuals in the United States had opioid use disorder in 2015,2 and approximately 80% of them received no treatment,3 even though effective treatment could reduce the scope of abuse.4,5

Although psychiatrists typically are not the primary prescribers of opioid medications, they often treat psychiatric disorders in patients with chronic pain who take prescription opioids. A recent study found that, despite representing only 16% of the adult population, adults with mental health disorders receive more than one-half of all opioid prescriptions distributed each year in the United States.6 Therefore, psychiatrists must be aware of risk assessment strategies for patients receiving opioids.

In this article, we provide recommendations for managing individuals with opioid use disorder, including:

  • how to identify risk factors for opioid use disorder and use screening tools
  • how to evaluate a patient with suspected opioid use disorder and make the diagnosis
  • how to treat a patient with opioid use disorder, including a review of approved pharmaceutical agents.

Risk factors for opioid abuse and overdose

Patients with a history of mental health and/or substance use disorders or at least 3 months of prescribed opioid treatment are at risk for opioid abuse. Those taking a high daily dose of opioids or who have a history of overdose are at risk for overdose from opioid abuse (Table 1).7-12 Standardized tools, such as the Opioid Risk Tool, can be used to screen to assess risk for opioid abuse among individuals prescribed opioids for treatment of chronic pain.12 However, clinicians must be aware that even patients without characteristic risk factors can become dependent on opioids and/or be at risk for an accidental or intentional overdose. For example, opioid therapy following surgical procedures, even in patients who do not have a history of opioid use, increases risk of developing opioid use disorder.13

Evaluation and diagnosis

DSM-5 criteria define 3 degrees of opioid use disorder, depending on how many of the following traits a patient exhibits (mild, 2 to 3; moderate, 4 to 5; and severe, ≥6 )14:

  • taking more than the initially intended quantities of opioids or for a longer period of time than intended
  • continuous attempts to reduce or otherwise manage opioid use or desires to do so
  • a great deal of time using, recovering from, or acquiring opioids
  • reports of strong cravings to use opioids
  • failing to meet personal objectives at home, work, or school
  • continued opioid use even though it causes recurrent social problems
  • reduction or elimination of activities the patient once considered important due to opioid use
  • opioid use in situations where it is physically dangerous
  • continued opioid use despite persistent psychological or physiologic problems despite knowing that continued use is causing or worsening those problems
  • tolerance to opioids (not consequential for the diagnosis if the patient is taking opioids under appropriate medical supervision)
  • withdrawal or use of opioids (or related substances) to prevent withdrawal (not consequential for the diagnosis if the patient is taking opioids under appropriate medical supervision).

Clinicians should be vigilant for symptoms of opioid use or withdrawal, such as needle marks and weight loss, during the interview (Table 2). High-risk populations that require regular screening include individuals with a history of opioid use disorder, patients taking chronic pain medication, and psychiatric patients.15 During the interview, clinicians should take an nonjudgmental approach and avoid “shame and blame.”


Patients often will withhold information about drug use for various reasons.16 Therefore, collateral information from the patient’s family, close friends, or a referral source is important.
 

Standardized scales. Various standardized scales can be used to evaluate patients for opioid withdrawal and risk for substance use disorder. Scales for assessing opioid withdrawal include:

  • Clinical Opiate Withdrawal Scale
  • Subjective Opiate Withdrawal Scale.

Substance use disorder screening tools include:

  • Drug Abuse Screen Test-10
  • Alcohol Use Disorders Identification Test
  • National Institute on Drug Abuse (NIDA) Drug Screening Tool.17

Examination findings. A brief physical examination is necessary to document key findings (Table 2). Patients should undergo a urine drug screen; gas chromatography/mass spectroscopy can confirm positive results. During the examination, clinicians should look for signs and symptoms of co-occurring substance use (eg, benzo­diazepines, marijuana, alcohol, cocaine) or mental disorders (mood, anxiety, attention-deficit).18-21 Because nonprescription opioid use is associated with increased risk of suicide attempts and ideation,22 a suicide risk assessment is necessary.

Managing opioid use disorder

Detoxification is a 3-tiered approach that requires judicious prescription of medication, psychosocial support, and supervision to relieve opioid withdrawal symptoms. In both inpatient and outpatient settings, medications used for opioid detoxification include buprenorphine, clonidine, and methadone administered in doses tapered over 5 to 7 days. Appropriate detoxification increases treatment retention for continuing care.23,24

Buprenorphine or buprenorphine/naloxone is the first-line option for outpatient and inpatient detoxification. Short-term detoxification schedules include starting doses between 4 and 16 mg/d, tapered over 5 to 7 days. Compared with methadone, buprenorphine has a lower risk of overdose25 and abuse potential and can be given in an office-based setting. Clonidine, 0.3 to 1.2 mg/d in divided doses, is an alternative to buprenorphine and can be used in in­patient settings.26

Clonidine is not as effective as buprenorphine for detoxification, but it may be used when buprenorphine is contraindicated. Clonidine may require adjuvant symptomatic treatment for insomnia (eg, trazodone, 100 mg at bedtime), anxiety (eg, hydroxyzine, 25 mg, twice a day), or diarrhea (loperamide, 2 mg/d). If a patient needs more structure and monitoring, he (she) should be referred for inpatient detoxification or to a methadone program.27

 

 

 

Medication-assisted therapies

Detoxification alone often is not sufficient treatment. Medication-assisted therapy (MAT) is typically recommended by federal guidelines provided by the Substance Abuse and Mental Health Administration (SAMHSA) for patients with opioid use disorders.3 Patients can be directly transitioned from currently abused opioids to MAT on an outpatient basis. FDA-approved medications for MAT for opioid use disorder include buprenorphine, naltrexone (oral and long-acting injectable), and methadone (Table 3). Choice of MAT depends on several factors, including cost, patient preference, and availability of methadone programs and buprenorphine providers.28

MAT should include psychosocial support29-33 and active monitoring with urine drug screens. Maintenance therapy with medications is usually long-term and has been shown to have better outcomes than detoxification alone or short-term treatment.34 Relapse during MAT should not be cause to discontinue treatment; instead, the patient should be referred to a higher level of care.

Some patients require individualized treatment approaches. For example, the SAMHSA has developed specific treatment improvement protocols to tailor treatments to address specific needs of adolescents.32 The American Academy of Pediatrics recommends MAT with buprenorphine in adolescents with opioid use disorder.33 Although methadone has been approved for pregnant, opioid-dependent patients, recent data indicate buprenorphine is as effective with lower intensity of neonatal abstinence syndrome.34

Buprenorphine. This long-acting (half-life of 24 to 42 hours) opioid partial agonist is approved for treating opioid use disorder in office-based settings according to the Drug Abuse Treatment Act of 2000. Buprenorphine is administered in doses of 8 to 16 mg/d in film or tablet form (sublingual or buccal) and is available in various formulations (Table 4). It is well tolerated; constipation and unpleasant taste are the most common adverse effects. Physicians are required to have a federal waiver to obtain the Drug Enforcement Administration license to prescribe buprenorphine for opioid use disorder in an office setting.

Buprenorphine reduces or eliminates cravings and withdrawal symptoms and helps improve outcomes of abstinence from opioids and retention in treatment.31 Formulations of naloxone combined with buprenorphine reduce the risk of abuse via injection.35 Buprenorphine is safe; however, overdoses can occur when it is combined with benzodiazepines and/or other opiates.

Methadone. This long-acting (half-life 8 to 59 hours), full opioid agonist is approved to treat opioid addiction in federal- and state-regulated opioid treatment programs, also known as methadone maintenance programs. These programs are highly structured and include intensive counseling, monitoring, and dispensing to reduce relapse. Methadone is administered orally either via powder, liquid concentrate, tablet, or solution of diskette. Typically, methadone is dispensed daily in doses of 60 to 100 mg, although higher doses are sometimes necessary. Patients who meet certain criteria for stability may be allowed to take home supplies of methadone.

Methadone has a “black-box” warning for overdose, QT prolongation, and risk for respiratory depression when used in combination with benzodiazepines. Because of its long and unpredictable half-life and tissue accumulation, methadone carries a high overdose risk, particularly with rapidly titrated doses during therapy initiation.35 However, most overdose deaths have occurred with methadone prescribed for pain management. When prescribed and monitored in an opioid treatment program, methadone has shown a high safety profile with respect to overdoses.36

Injectable and oral naltrexone. Used for prevention of relapse to opioid dependence, naltrexone is a pure opioid antagonist that is available as an oral or IM form. Naltrexone has high affinity for the opioid receptors and in therapeutic doses provides an effective blockade for heroin or opioids. Compliance with oral naltrexone has been poor, leading to development of an IM form of naltrexone that can be administered as a single 380-mg dose once every 4 weeks for 6 months or sometimes longer. Naltrexone is also approved for alcohol dependence.

To avoid precipitated withdrawal, patients should be detoxified from opioids for 7 to 10 days before they begin naltrexone, which has no potential for abuse. Common adverse effects include fatigue, nausea, headache, and, for the IM formulation, injection site reactions. There is a “black-box” warning for liver toxicity; therefore, baseline and periodic liver function tests are necessary.

A NIDA review reported poor compliance with oral naltrexone compared with methadone.35 However, naltrexone has been shown to be effective in highly motivated patients (eg, impaired physicians) and the criminal justice population and for preventing relapse following taper from buprenorphine or methadone.37,38

Treatment for opioid overdose

Naloxone is a highly effective treatment to reverse opioid overdose that is delivered via IM or IV injection or by nasal application. Naloxone has no abuse potential. In doses of 0.4 to 2 mg, naloxone reverses overdose within 2 minutes and is effective for 30 to 90 minutes.39 One should call 911 as soon as possible after naloxone is administered. In several states, naloxone is available without a prescription for patients and family members to combat opioid overdoses. The CDC recommends offering naloxone to patients who have risk factors for opioid overdose.40

Bottom Line

The epidemic of opioid abuse and overdose has emphasized the importance of recognition and treatment of opioid use disorder. Buprenorphine/naloxone, methadone, and naltrexone formulations are approved treatments for opioid use disorder. Naloxone formulations are approved to treat opioid overdoses. Effective medication-assisted treatment should be long-term and include behavioral interventions and psychosocial support.

Related Resources

  • Rudd RA, Seth P, David F, et al. Increases in drug and opioid-involved overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(5051):1445-1452.
  • Nielsen S, Larance B, Degenhardt L, et al. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev. 2016;(5):CD011117. doi: 10.1002/14651858.CD011117.pub2.
  • Timko C, Schultz NR, Cucciare MA, et al. Retention in medication-assisted treatment for opiate dependence: a systematic review. J Addict Dis. 2016;35(1):22-35.

Drug Brand Names

Buprenorphine/naloxone • Suboxone, Subutex
Methadone • Dolophine
Naltrexone • Revia, Vivitrol
Naloxone • Narcan, Evzio

References

1. Centers for Disease Control and Prevention. Opioid data analysis. http://www.cdc.gov/drugoverdose/data/analysis.html. Updated February 9, 2017. Accessed June 27, 2017.
2. Substance Abuse and Mental Health Services Administration. Results from the 2015 National Survey on Drug Use and Health: detailed tables. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.pdf.
3. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment of opioid use disorder pocket guide. https://store.samhsa.gov/shin/content//SMA16-4892PG/SMA16-4892PG.pdf. Accessed June 29, 2017.
4. Mutlu C, Demirci AC, Yalcin O, et al. One-year follow-up of heroin-dependent adolescents treated with buprenorphine/naloxone for the first time in a substance treatment unit. J Subst Abuse Treat. 2016;67:1-8.
5. Sharma B, Bruner A, Barnett G, et al. Opioid use disorders. Child Adolesc Psychiatr Clin N Am. 2016;25(3):473-487.
6. Davis MA, Lin LA, Liu H, Sites BD. Prescription Opioid Use among Adults with mental health disorders in the United States. J Am Board Fam Med. 2017;30:42-47.
7. Icahn School of Medicine at Mount Sinai. Substance use: prescription drugs. http://www.mountsinai.org/patient-care/health-library/diseases-and-conditions/opioid-abuse#risk. Accessed June 27, 2017.
8. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction. 2010;105(10):1776-1782.
9. Edlund M, Steffick D, Hudson T, et al. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007;129(3):355-362.
10. Compton WM, Volkow ND. Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug Alcohol Depend. 2006;81(2):103-107.
11. Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315-1321.
12. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):432.
13. Sun EC, Darnall BD, Baker LC, et al. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med. 2016;176(9):1286-1293.
14. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
15. Starrels JL, Becker WC, Alford DP, et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Internal Med. 2010;152(11):712-720.
16. Substance Abuse and Mental Health Services Administration. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction: a treatment improvement protocol: TIP 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004.
17. NIDA drug screening tool: clinician’s screening tool for drug use in general medical settings. National Institutes of Health. https://www.drugabuse.gov/nmassist. Accessed June 27, 2017.
18. Fareed A, Eilender P, Haber M, et al. Comorbid posttraumatic stress disorder and opiate addiction: a literature review. J Addict Dis. 2013;32(2):168-179.
19. Rosen D, Smith ML, Reynolds CF 3rd. The prevalence of mental and physical health disorders among older methadone patients. Am J Geriatr Psychiatry. 2008;16(6):488-497.
20. Goldner EM, Lusted A, Roerecke M, et al. Prevalence of Axis-1 psychiatric (with focus on depression and anxiety) disorder and symptomatology among non-medical prescription opioid users in substance use treatment: systematic review and meta-analyses. Addict Behav. 2014;39(3):520-531.
21. Barry DT, Cutter CJ, Beitel M, et al. Psychiatric disorders among patients seeking treatment for co-occurring chronic pain and opioid use disorder. J Clin Psychiatry. 2016;77(10):1413-1419.
22. Kuramoto SJ, Chilcoat HD, Ko J, et al. Suicidal ideation and suicide attempt across stages of nonmedical prescription opioid use and presence of prescription opioid disorders among U.S. adults. J Stud Alcohol Drugs. 2012;73(2):178-184.
23. Mattick RP, Breen C, Kimber J, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;(2):CD002207. doi: 10.1002/14651858.CD002207.pub4.
24. Evans E, Li L, Min J, et al. Mortality among individuals accessing pharmacological treatment for opioid dependence in California, 2006-10. Addiction. 2015;110(6):996-1005.
25. Marteu D, McDonald R, Patel K. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales. BMJ Open. 2015;5(5):e007629. doi: 10.1136/bmjopen-2015-007629.
26. Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal. Differential effects on signs and symptoms. Arch Gen Psychiatry. 1985;42(11):1063-1066.
27. Whelan PJ, Remski K. Buprenorphine vs methadone treatment: a review of evidence in both developed and developing worlds. J Neurosci Rural Pract. 2012;3(1):45-50.
28. Schuckit MA. Treatment of opioid-use disorders. N Engl J Med. 2016;375(4):357-368.
29. Dutra L, Stathopoulou G, Basden SL, et al. A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry. 2008;165(2):179-187.
30. Brown HL, Britton KA, Mahaffey D, et al. Methadone maintenance in pregnancy: a reappraisal. Am J Obstet Gynecol. 1998;179(2):459-463.
31. Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) 43. HHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2005.
32. Zimlich R. AAP recommends on medication assisted therapy for adolescent opioid addiction. Contemporary Pediatrics. http://contemporarypediatrics.modernmedicine.com/contemporary-pediatrics/news/aap-recommends-medication-assisted-therapy-adolescent-opioid-addiction. Published September 15, 2016. Accessed June 29, 2017.
33. Patkar A, Lee J, Burgess D. Opioid use disorder. BMJ Publishing Group. http://bestpractice.bmj.com/best-practice/monograph/200.html. Published 2015. Accessed July 6, 2017.
34. Alho H, Sinclair D, Vuori E, et al. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend. 2007;88(1):75-78.
35. Centers for Disease Control and Prevention (CDC). Vital signs: risk for overdose from methadone used for pain relief - United States, 1999-2010. MMWR Morb Mortal Wkly Rep. 2012;61(26):493-497.
36. Soyka M. New developments in the management of opioid dependence: focus on sublingual buprenorphine-naloxone. Subst Abuse Rehabil. 2015;6:1-14.
37. Lee JD, Friedmann PD, Kinlock TW, et al. Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders N Engl J Med. 2016;374(13):1232-1242.
38. Vo HT, Robbins E, Westwood M, et al. Relapse prevention medications in community treatment for young adults with opioid addiction. Subst Abus. 2016;37(3):392-397.
39. McDonald R, Campbell ND, Strang J. Twenty years of take-home naloxone for the prevention of overdose deaths from heroin and other opioids-conception and maturation. Drug Alcohol Depend. 2017;178:176-187.
40. Centers for Disease Control and Prevention. Overdose prevention. https://www.cdc.gov/drugoverdose/opioids/odprevention.html. Updated February 9, 2017. Accessed July 6, 2017.

References

1. Centers for Disease Control and Prevention. Opioid data analysis. http://www.cdc.gov/drugoverdose/data/analysis.html. Updated February 9, 2017. Accessed June 27, 2017.
2. Substance Abuse and Mental Health Services Administration. Results from the 2015 National Survey on Drug Use and Health: detailed tables. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.pdf.
3. Substance Abuse and Mental Health Services Administration. Medication-assisted treatment of opioid use disorder pocket guide. https://store.samhsa.gov/shin/content//SMA16-4892PG/SMA16-4892PG.pdf. Accessed June 29, 2017.
4. Mutlu C, Demirci AC, Yalcin O, et al. One-year follow-up of heroin-dependent adolescents treated with buprenorphine/naloxone for the first time in a substance treatment unit. J Subst Abuse Treat. 2016;67:1-8.
5. Sharma B, Bruner A, Barnett G, et al. Opioid use disorders. Child Adolesc Psychiatr Clin N Am. 2016;25(3):473-487.
6. Davis MA, Lin LA, Liu H, Sites BD. Prescription Opioid Use among Adults with mental health disorders in the United States. J Am Board Fam Med. 2017;30:42-47.
7. Icahn School of Medicine at Mount Sinai. Substance use: prescription drugs. http://www.mountsinai.org/patient-care/health-library/diseases-and-conditions/opioid-abuse#risk. Accessed June 27, 2017.
8. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction. 2010;105(10):1776-1782.
9. Edlund M, Steffick D, Hudson T, et al. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007;129(3):355-362.
10. Compton WM, Volkow ND. Major increases in opioid analgesic abuse in the United States: concerns and strategies. Drug Alcohol Depend. 2006;81(2):103-107.
11. Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315-1321.
12. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):432.
13. Sun EC, Darnall BD, Baker LC, et al. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med. 2016;176(9):1286-1293.
14. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
15. Starrels JL, Becker WC, Alford DP, et al. Systematic review: treatment agreements and urine drug testing to reduce opioid misuse in patients with chronic pain. Ann Internal Med. 2010;152(11):712-720.
16. Substance Abuse and Mental Health Services Administration. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction: a treatment improvement protocol: TIP 40. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2004.
17. NIDA drug screening tool: clinician’s screening tool for drug use in general medical settings. National Institutes of Health. https://www.drugabuse.gov/nmassist. Accessed June 27, 2017.
18. Fareed A, Eilender P, Haber M, et al. Comorbid posttraumatic stress disorder and opiate addiction: a literature review. J Addict Dis. 2013;32(2):168-179.
19. Rosen D, Smith ML, Reynolds CF 3rd. The prevalence of mental and physical health disorders among older methadone patients. Am J Geriatr Psychiatry. 2008;16(6):488-497.
20. Goldner EM, Lusted A, Roerecke M, et al. Prevalence of Axis-1 psychiatric (with focus on depression and anxiety) disorder and symptomatology among non-medical prescription opioid users in substance use treatment: systematic review and meta-analyses. Addict Behav. 2014;39(3):520-531.
21. Barry DT, Cutter CJ, Beitel M, et al. Psychiatric disorders among patients seeking treatment for co-occurring chronic pain and opioid use disorder. J Clin Psychiatry. 2016;77(10):1413-1419.
22. Kuramoto SJ, Chilcoat HD, Ko J, et al. Suicidal ideation and suicide attempt across stages of nonmedical prescription opioid use and presence of prescription opioid disorders among U.S. adults. J Stud Alcohol Drugs. 2012;73(2):178-184.
23. Mattick RP, Breen C, Kimber J, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;(2):CD002207. doi: 10.1002/14651858.CD002207.pub4.
24. Evans E, Li L, Min J, et al. Mortality among individuals accessing pharmacological treatment for opioid dependence in California, 2006-10. Addiction. 2015;110(6):996-1005.
25. Marteu D, McDonald R, Patel K. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales. BMJ Open. 2015;5(5):e007629. doi: 10.1136/bmjopen-2015-007629.
26. Jasinski DR, Johnson RE, Kocher TR. Clonidine in morphine withdrawal. Differential effects on signs and symptoms. Arch Gen Psychiatry. 1985;42(11):1063-1066.
27. Whelan PJ, Remski K. Buprenorphine vs methadone treatment: a review of evidence in both developed and developing worlds. J Neurosci Rural Pract. 2012;3(1):45-50.
28. Schuckit MA. Treatment of opioid-use disorders. N Engl J Med. 2016;375(4):357-368.
29. Dutra L, Stathopoulou G, Basden SL, et al. A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry. 2008;165(2):179-187.
30. Brown HL, Britton KA, Mahaffey D, et al. Methadone maintenance in pregnancy: a reappraisal. Am J Obstet Gynecol. 1998;179(2):459-463.
31. Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) 43. HHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2005.
32. Zimlich R. AAP recommends on medication assisted therapy for adolescent opioid addiction. Contemporary Pediatrics. http://contemporarypediatrics.modernmedicine.com/contemporary-pediatrics/news/aap-recommends-medication-assisted-therapy-adolescent-opioid-addiction. Published September 15, 2016. Accessed June 29, 2017.
33. Patkar A, Lee J, Burgess D. Opioid use disorder. BMJ Publishing Group. http://bestpractice.bmj.com/best-practice/monograph/200.html. Published 2015. Accessed July 6, 2017.
34. Alho H, Sinclair D, Vuori E, et al. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend. 2007;88(1):75-78.
35. Centers for Disease Control and Prevention (CDC). Vital signs: risk for overdose from methadone used for pain relief - United States, 1999-2010. MMWR Morb Mortal Wkly Rep. 2012;61(26):493-497.
36. Soyka M. New developments in the management of opioid dependence: focus on sublingual buprenorphine-naloxone. Subst Abuse Rehabil. 2015;6:1-14.
37. Lee JD, Friedmann PD, Kinlock TW, et al. Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders N Engl J Med. 2016;374(13):1232-1242.
38. Vo HT, Robbins E, Westwood M, et al. Relapse prevention medications in community treatment for young adults with opioid addiction. Subst Abus. 2016;37(3):392-397.
39. McDonald R, Campbell ND, Strang J. Twenty years of take-home naloxone for the prevention of overdose deaths from heroin and other opioids-conception and maturation. Drug Alcohol Depend. 2017;178:176-187.
40. Centers for Disease Control and Prevention. Overdose prevention. https://www.cdc.gov/drugoverdose/opioids/odprevention.html. Updated February 9, 2017. Accessed July 6, 2017.

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