PRESCRIBING OPIOIDS IN PATIENTS WITH SUBSTANCE USE DISORDER*

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This module provides information about substance use disorder as a risk factor for opioid overdose and specific risk-reduction guidance. It supplements but does not replace the general best practices for opioid prescribing presented in the “Considerations for Safe and Responsible Opioid Prescribing”module.

Background

  1. Addiction is a primary, chronic disease characterized by impaired behavioral control of substance use, craving, and diminished recognition of significant problems with one’s behaviors and interpersonal relationships. Like other chronic diseases, addiction often involves cycles of relapse and remission.1-3
    1. The DSM-V identifies 11 criteria to consider when diagnosing opioid use disorder (OUD). (DSM-V, also see ‘Additional Resources’ #1)
      1. The presence of 2-3 criteria within a 12-month period indicates mild OUD, 4-5 indicate moderate OUD, and 6 or more indicate severe OUD. (DSM-V)
    2. For individuals taking prescription opioids under medical supervision, two criteria (tolerance and withdrawal) do not count toward an OUD diagnosis. Tolerance is defined by the “need for increased amounts of opioids or diminished effect with continued use at the same amount,” and withdrawal is defined by “characteristic opioid withdrawal syndrome or taking opioids to relieve or avoid withdrawal symptoms.” (DSM-V)

Updated addiction-related terminology (selected terms)§

Current (2018) Former
Substance use disorder (SUD) (DSM-5) Substance abuse + substance dependence (DSM-IV)
Opioid use disorder (OUD) (DSM-5) Opioid abuse + opioid dependence (DSM-IV)
Misuse Abuse, nonmedical use
OUD pharmacotherapy, OUD medication Medication assisted treatment
Medically supervised withdrawal Detoxification
Recovery (includes remission)
Return to opioid use Relapse

§For definitions of these and additional terms see SAMHSA 2018 (p1-16), DHHS USSG 2016 (ch2), or DSM-V. (see ‘Additional Resources’ for a summary of various definitions of selected terminology)

  1. Pharmacotherapy with buprenorphine, methadone, or naltrexone should be considered for all persons with OUD in conjunction withpsychosocial treatment (e.g., psychotherapeutic counseling, contingency vmanagement, community reinforcement, and family therapy).2,5,6
    1. OUD pharmacotherapy as part of a comprehensive treatment plan for OUD reduces illicit opioid use, increases retention in treatment, and reduces risk of opioid overdose death when compared to treatment without medication.
    2. Buprenorphine and methadone are indicated to manage withdrawal and treat OUD.
    3. Naltrexone is an opioid antagonist used in persons in recovery from OUD to diminish opioid effects and prevent relapse.
  2. Buprenorphine, a partial mu opioid receptor (MOR) agonist, is a pharmacologically safer opioid (Schedule III) than pure MORs such as morphine or methadone (Schedule II).1,2,7
    1. Partial agonists bind and activate MORs to a lesser degree than full agonists.
    2. Thus, buprenorphine reaches a maximum (ceiling) effect at a certain dose for both analgesic and respiratory depressant effects.
    3. Buprenorphine has a higher binding affinity for the MOR than most full opioid agonists and it can displace or block full agonists from MORs.
    4. If buprenorphine is administered to a patient who is physically dependent on full mu agonist opioids, the patient may experience precipitated withdrawal if insufficient time has elapsed since their last dose of the full agonist opioid.
  3. Methadone (see “Methadone” module)

 

Substance use disorder (SUD) and opioid overdose

  1. A personal history of an SUD is the strongest and most consistent risk factor for developing opioid misuse or OUD when prescribed opioids. Family history of SUD also increases risk, suggesting that individuals are predisposed to SUD due to genetic and external factors.3,8,9
  2. Individuals with a history of SUD frequently have co-occurring mental health disorders, poor adherence to psychotherapeutic treatment, and increased risk-taking behavior that increase their risk for OUD and overdose compared with persons without such conditions.3,10-12
  3. Opioid use disorder is often accompanied by use of other substances. Concurrent use or misuse of other central nervous system (CNS) depressant medications or substances such as alcohol or benzodiazepines may lead to life-threatening respiratory depression or over-sedation (overdose) which is most commonly unintentional.5,10-13
  4. Recent periods of opioid abstinence, particularly in a controlled environment such as during incarceration or hospitalization, are major risk factors for fatal opioid overdose in individuals with OUD.
    1. The person may lose tolerance to their prior opioid dose in as little as one week, and the risk for a serious overdose is high if they suddenly resume their prior opioid dose.14,15

 

Risk-mitigation interventions to consider when prescribing opioid analgesics in patients with SUD

[Refer to the full prescribing information (FDA Label) for important product-specific details]

         A.Assessment1,16

  1. Review the patient’s medical records and obtain their self-report of all recent use (past 30 days and particularly the past 1 to 2 days) of prescribed controlled medications and substances, including types (tobacco included), amounts, frequency, and duration.
  2. Conduct urine (or saliva) drug testing to check for the presence of prescribed controlled medications (adherence) and to detect undisclosed use of non-prescribed controlled medications or illicit drugs (misuse/addiction).
  3. Check the state prescription drug monitoring program (PDMP) data from the patient’s home and surrounding states to confirm the history of controlled medications and to investigate use of multiple prescribers or pharmacies, which raise concern for substance use disorder or diversion.
  4. Assess for a DSM-5 diagnosis of currently active SUD if the patient has a history of SUD, recent controlled substance misuse, or recent illicit substance use.

         B.Treatment: Pain management in patients with SUD1,2,16

  1. Optimize treatment of co-occurring mental health disorders (anxiety, depression).
  2. Optimize non-pharmacologic interventions to manage pain.
  3. Optimize treatment with non-opioid analgesics such as acetaminophen, NSAIDs/cyclooxygenase 2 (COX-2) inhibitors, topical analgesics, and adjuvant analgesics (selected antidepressants, such as tricyclics and serotonin-norepinephrine reuptake inhibitors; and selected anticonvulsants, such as gabapentin and pregabalin).
  4. Strongly consider consulting a pain medicine or addiction medicine specialist regarding pain management for persons with active or recent SUD. Communicate with the patient’s SUD treatment providers if opioid analgesics are prescribed.5
  5. Prescribe take-home naloxone for opioid-treated persons with a history of SUD, including those who have recently initiated OUD pharmacotherapy, to reverse life-threatening respiratory depression if an overdose occurs. Educate the patient, family/household members, and caregivers about signs and symptoms of opioid overdose and train them to properly use naloxone if an opioid-related overdose is suspected.5,17,18 (See ‘Follow Up’ section, #5 in the “Considerations for Safe and Responsible Opioid Prescribing”module)
  6. Patients with pain and active, untreated OUD:
    1. Defer treatment of pain beyond non-opioid interventions until OUD pharmacotherapy is initiated and the patient consents to care in collaboration with the patient’s OUD treatment provider (if a different clinician).2,6,19
    2. Initiate or refer for OUD pharmacotherapy—which can also help manage pain—in conjunction with psychosocial treatment.
      1. Methadone to treat OUD may be dispensed only by a certified opioid treatment program.
      2. Buprenorphine therapy may be prescribed for patients with OUD by trained and certified health care professionals with a DATA waiver/DEA “X” license in most office-based settings in accordance with the Drug Addiction and Treatment Act (DATA 2000).2
  7. Patients with OUD who are in medication-assisted recovery with buprenorphine pharmacotherapy:
    1. Defer treatment of pain beyond non-opioid interventions until the patient consents to care in collaboration with the patient’s OUD treatment provider.2,6,19
    2. Buprenorphine to treat OUD may also provide modest analgesia for a co-occurring pain condition and should be continued without interruption.
    3. For mild-to-moderate acute pain, consider temporarily dividing the total buprenorphine dose to three times per day to improve pain relief, as buprenorphine’s analgesic effect only lasts 6 to 8 hours.
    4. If pain relief is inadequate or if the acute pain is moderate to severe, first confirm that the patient is taking buprenorphine by urine drug testing using a method that is designed to detect synthetic opioids like buprenorphine. If confirmed, the daily dose of buprenorphine (sublingual) may be increased to a maximum of 24mg per day.
    5. If pain relief is inadequate, consult a specialist in pain medicine or addiction medicine regarding pain management.5
  8. Patients with OUD who are in medication-assisted recovery with methadone pharmacotherapy:
    1. Defer treatment of pain beyond non-opioid interventions until the patient consents to care in collaboration with the patient’s OUD treatment provider.2,6,19
    2. Contact the patient’s opioid treatment program (OTP) directly to confirm the patient’s methadone dose and the last day of dose administration. Confirm recent use of the methadone with a urine drug screen that is able to detect synthetic opioids. Maintenance methadone for OUD should be continued without interruption as it also may provide analgesia for a co-occurring pain condition.
    3. Suggest that the OUD treatment provider consider dividing the methadone dose to every 6-12 hours to improve pain relief. The analgesic effect of methadone lasts only 4 to 8 hours in comparison with its typical daily dosing schedule for the treatment of OUD and half-life of approximately 24 to 36 hours (range, 8 to 59 hours).
    4. For pain severe enough to require opioid analgesics in patients who are administered daily methadone maintenance to treat OUD, additional doses and higher opioid analgesic dosage will likely be necessary for pain control due to opioid tolerance. If considering prescribing opioid analgesics in the outpatient setting for a patient enrolled in an OTP, coordinate treatment with the OTP provider and prescribe short-acting opioids as time-scheduled treatment rather than as-needed.
  9. Patients with a remote history of OUD (e.g., in long-term remission without OUD pharmacotherapy):
    1. If pain control of a chronic pain condition with non-opioid therapy is inadequate, a trial of an opioid analgesic may be considered in consultation with pain medicine and addiction medicine specialists, with very close monitoring of patient medication adherence, and weighing the pain and functional benefits against the increased risks of overdose and active OUD.5,16

 

Additional Resources

*The information presented in this module highlights some fundamental concepts of opioid prescribing for adult outpatients. It excludes certain populations (pediatrics, pregnancy, patients with active cancer or receiving palliative or end-of-life care) and settings (perioperative, emergency, in-patient). The information provided is intended to support safe and effective opioid therapy and minimize serious adverse outcomes, particularly overdose. It is not intended to be exhaustive nor substitute for consulting a medication’s full prescribing information for complete details and warnings. Links and references to selected, more comprehensive clinical and prescribing resources are provided to facilitate safe and effective opioid prescribing.

  1. DSM-V Criteria for Substance Use Disorder, DSM-V Criteria for Opioid Use Disorder, DSM-V Opioid Use Disorder Checklist
  2. FDA-approved drug label information: FDA Online Label Repository or Daily Med (NIH/National Library of Medicine)
  3. Behavioral Health Treatment Services Locator. A confidential and anonymous source of information for persons seeking treatment facilities for SUD and/or mental health problems
    1. Opioid Treatment Program Locator for methadone treatment programs
    2. Buprenorphine Physician and Treatment Program Locator
  4. Buprenorphine Resource Centerand training for eligible office-based health care professionals to become certified to prescribe buprenorphine for patients with OUD under the Drug Addiction Treatment Act of 2000 (DATA 2000)
  5. American Society of Addiction Medicine
    1. American Society of Addiction Medicine SUD treatment resources
    2. The ASAM criteria. The most widely used and comprehensive set of guidelines for placement, continued stay and transfer/discharge of patients with addiction and co-occurring conditions
  6. National Institute on Drug Abuse
    1. NIDA Resources for Health Care Professionals
    2. Pain Management, Opioid, and Addiction Science Resources
  1. Opioid Abuse in Chronic Pain—Misconceptions and Mitigation Strategies.20
  2. PCSS-O Training – Prescribers’ Clinical System for Opioid Therapies
  3. Prescriber Clinical Support System for Medication Assisted Treatment
  4. Opioid Overdose Prevention Toolkit (SAMHSA) How to help prevent opioid-related overdoses and deaths for first responders, healthcare professionals, and persons recovering from opioid overdose
  5. Prescribe to prevent Overdose education and naloxone prescribing and dispensing information
  6. SCOPE of Pain (Boston University) Safe and Competent Opioid Prescribing Education

 

Summary of various definitions of selected terminology3

 

References

  1. American Society of Addiction Medicine. National Practice Guideline for the use of medications in the treatment of addiction involving opioid use. ASAM 2015
  2. Substance Abuse and Mental Health Services Administration. Medications to Treat Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63, Full Document. HHS Publication No. (SMA) 18-5063FULLDOC. Rockville, MD: SAMHSA Tip 63.
  3. S. Department of Health and Human Services (HHS), Office of the Surgeon General, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS, November 2016. DHHS USSG 2016 Report.
  4. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569-76. PMID: 25785523
  5. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain – United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. PMID: 26987082
  6. S. Department of Veteran Affairs, Department of Defense. Clinical Practice Guideline for the Management of Substance Use Disorders. Veterans Health Administration; Revised December 2015. VA/DoD Management of Substance Use Disorders
  7. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004.
  8. Edlund MJ, Steffick D, Hudson T, Harris KM, Sullivan M. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007;129(3):355-62. PMID: 17449178
  9. Ives TJ, Chelminski PR, Hammett-Stabler CA, Malone RM, Perhac JS, Potisek NM, et al. Predictors of opioid misuse in patients with chronic pain: a prospective cohort study. BMC Health Serv Res. 2006;6:46. PMID: 16595013
  10. Bohnert AS, Ilgen MA, Ignacio RV, McCarthy JF, Valenstein M, Blow FC. Risk of death from accidental overdose associated with psychiatric and substance use disorders. Am J Psych 2012;169:64-70. PMID: 21955932
  11. Nadpara PA, Joyce AR, Murelle EL, et al. Risk factors for serious prescription opioid induced respiratory depression or overdose: Comparison of commercially insured and veterans health affairs populations. Pain Medicine 2018;19:79-86. PMID: 28419384
  12. Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-related toxicity or overdose among veterans health administration patients. Pain Med. 2014;15:1911-1929. PMID: 24931395
  13. Passik SD, Lowery A. Psychological variables potentially implicated in opioid related mortality as observed in clinical practice. Pain Medicine 2011;12: S36-S42. PMID: 21668755
  14. Binswanger IA, Stern MF, Deyo RA, Heagerty PJ, Cheadle  A, Elmore  JG, et al. Release from Prison — A High Risk of Death for Former Inmates. New England Journal of Medicine. 2007;356(2):157-65. PMID: 17215533
  15. Strang J, McCambridge J, Best D, et al. Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study. BMJ 2003; 326: 959-960. PMID: 12727768
  16. Substance Abuse and Mental Health Services Administration. Managing Chronic Pain in Adults with or in Recovery Form Substance Use Disorders, Treatment Improvement Tip 54. SAMHSA 2012. SAMHSA Tip 54
  17. Federation of State Medical Boards (FSMB). Guidelines for the Chronic Use of Opioid Analgesics. April 2017. Federation of State Medical Boards
  18. Washington State Agency Medical Directors’ Group (WSAMDG). Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain: An Educational Aid to Improve Care and Safety With Opioid Treatment. Corvallis, WA: Washington Department of Health, 2015. Washington State Agency Medical Director’s Group
  19. Volkow N, Benveniste H, McLellan AT. Use and Misuse of Opioids in Chronic Pain. Annu Rev Med. 2018;69:451-65. PMID:29029586
  20. Volkow ND, McLellan AT. Opioid Abuse in Chronic Pain–Misconceptions and Mitigation Strategies. N Engl J Med. 2016;374(13):1253-63. PMID: 27028915