PRESCRIBING OPIOIDS FOR PATIENTS WITH BIPOLAR DISORDER OR SCHIZOPHRENIA*

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This module provides additional details about bipolar disorder or schizophrenia as risk factors 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. Chronic pain and mental health disorders are common in the general population, and they are often comorbid.1-3 Patients with co-occurring chronic pain and mental health disorders:
  2. Have greater intensity and longer duration of pain, poorer clinical outcomes, and increased health care utilization compared with those with either condition alone.4-7
  3. Are more likely to be treated with opioids, to receive a higher potency opioid or a higher opioid dose, and/or to have a longer duration (>90 days) of opioid therapy than those without mental health disorders.8-10
  4. There is high prevalence of lifetime alcohol and substance use disorders among patients with bipolar disorder or schizophrenia.11-13

 

Bipolar disorder, schizophrenia, and opioid overdose

  1. Individuals with a mental health disorder have greater risk for drug overdose.4,14-18
  2. Bipolar disorder is associated with impulsive behavior, recklessness, and generally increased risk-taking behavior.19
  3. Lack of insight combined with poor judgment leads an individual to engage in risky activities, partly explaining medication non-adherence during a manic episode, and an increased risk of overdose due to combined use of prescribed and misused drugs.20
  4. During manic or hypomanic episodes, patients with co-occurring substance use disorder commonly self-medicate with opioids or other central nervous system (CNS) depressants such as alcohol.19 Frequently referred to as “chemical coping,” this may be an attempt to counter rage, aggression, or dysphoria during such episodes.21
  5. In bipolar disorder, mixed states represent dangerous and potentially deadly combinations of depressed affect, impaired cognition and judgment, dysphoria, and increased energy level and impulsivity.19
  6. Many psychotherapeutic medications that are commonly used to treat bipolar disorder or schizophrenia are sedating, and can increase the risk of CNS and respiratory depression when used with opioids. Examples include benzodiazepines, sedatives/hypnotics, and certain antipsychotics, antidepressants, anticonvulsants, and anticholinergics.17,18 (see also: FDA label)
  7. In patients with inadequately treated pain, emotional or psychological distress is common and may be accentuated in patients with co-occurring mental health disorders. Pain is often resolved or reduced if the psychiatric comorbidity is well-managed.22

 

Risk-mitigation interventions to consider when prescribing opioids for patients with bipolar disorder or schizophrenia:

(Refer to the full prescribing information in the FDA label for important product-specific details)

  1. Avoid concurrent use of other medications or substances that are CNS depressants, such as benzodiazepines, sedatives/hypnotics, and alcohol in opioid-treated patients with bipolar disorder and schizophrenia. These combinations can result in profound sedation, respiratory depression, coma, and death, and should be restricted to the minimum required dosage and duration in patients for whom alternative treatment options are inadequate or contraindicated.16,22,23 (see also: FDA label)
  2. Before considering opioids to manage chronic non-cancer pain in individuals with acute psychiatric instability, consult or refer to a behavioral/mental health specialist.14,16,22,24
  3. Co-manage with a behavioral/mental health specialist (psychiatrist) those patients with bipolar disorder or schizophrenia who also have pain severe enough to require opioids.16,22,25
  4. Prescribe a lower initial dose of an opioid for patients who are already taking a CNS depressant.26
  5. If the patient is already taking an opioid, prescribe a lower initial dose of the psychotherapeutic medication(s) than otherwise would be indicated.
    1. NOTE: Anticonvulsants to treat epilepsy are the exception.
  6. If necessary, slowly titrate the dose of the opioid (or psychotherapeutic medication) to optimize outcomes (adequate analgesia and control of bipolar disorder or schizophrenia, with adequate tolerability/minimal adverse effects).
  7. Closely monitor the patient for respiratory depression or over-sedation during opioid initiation and after dosage escalation. The risk for overdose is greatest at this time because tolerance to an opioid’s respiratory depressant effects is slower to develop and less complete than tolerance to its analgesic or euphoric effects.16,23,27,28 Incorporate bio-behavioral approaches to limit opioid misuse and abuse by patients with co-morbid mental health issues.
  8. Check the PDMP to confirm that the patient is not obtaining controlled medications from multiple prescribers (or pharmacies). Check that the patient is securely storing and safely disposing of unused controlled medications.16 (see “Considerations for Safe and Responsible Opioid Prescribing” module)
  9. Determine whether a caregiver is needed to responsibly co-manage medication therapy.16 Collaborate closely with the patient, patient’s caregiver (if applicable), and pharmacist to ensure safe use of opioids and other medications.
  10. If tapering or discontinuing opioid therapy in patients with bipolar disorder or schizophrenia, monitor closely for emergent anxiety, depression, destabilization of the mental health disorder, suicidality, or unmasked opioid use disorder (i.e., aberrant opioid use behaviors), especially in patients treated with opioids long-term or at high opioid dosages.16,23
  11. Co-manage opioid tapering with a behavioral/mental health specialist. Refer patients who experience destabilization or serious challenges in tapering to a structured multidisciplinary program, if local resources are available.25
  12. Consider prescribing take-home naloxone to opioid-treated patients with bipolar disorder or schizophrenia 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.16,30

 

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. FDA-approved drug label information: FDA Online Label Repository or Daily Med (NIH/National Library of Medicine)
  2. Bipolar disorder guideline. APA 2010.
  3. Bipolar disorder treatment guidelines. British Association for Psychopharmacology 2016
  4. Schizophrenia practice guideline. APA 2010
  5. Depression and Bipolar Support Alliance
  6. International Society for Bipolar Disorders
  7. Schizophrenia Research Forum

 

References       

  1. Henschke N, Kamper SJ, Maher CG. The epidemiology and economic consequences of pain. Mayo Clin Proc 2015;90:139-47. PMID: 25572198
  2. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617-627. PMID: 15939839
  3.  Steel Z, Marnane C, Iranpour C, et al. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013. Int J Epidemiol. 2014;43(2):476-493. PMID: 24648481
  4. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med 2003;163:2433-45. PMID: 14609780
  5. Grattan A, Sullivan MD, Saunders KW, Campbell CI, Von Korff MR. Depression and prescription opioid misuse among chronic opioid therapy recipients with no history of substance abuse. Ann Fam Med. 2012;10(4):304-11. PMID: 22778118
  6. Gerrits MM, Vogelzangs N, van Oppen P, van Marwijk HW, van der Horst H, Penninx BW. Impact of pain on the course of depressive and anxiety disorders. Pain. 2012;153(2):429-36. PMID: 20026946
  7. Kroenke K, Outcalt S, Krebs E, Bair MJ, Wu J, Chumbler N, et al. Association between anxiety, health-related quality of life and functional impairment in primary care patients with chronic pain. Gen Hosp Psychiatry. 2013;35(4):359-65. PMID: 23639186
  8. Edlund MJ, Martin BC, Devries A, Fan MY, Braden JB, Sullivan MD. Trends in use of opioids for chronic noncancer pain among individuals with mental health and substance use disorders: the TROUP study. Clin J Pain 2010;26:1-8. PMID: 20026946
  9. Seal KH, Shi Y, Cohen G, Cohen BE, Maguen S, Krebs EE, et al. Association of mental health disorders with prescription opioids and high-risk opioid use in US veterans of Iraq and Afghanistan. JAMA. 2012;307(9):940-7. PMID: 22396516
  10. Sullivan MD, Edlund MJ, Steffick D, Unutzer J. Regular use of prescribed opioids: association with common psychiatric disorders. Pain 2005;119(1-3):95-103. PMID: 1629806
  11. McElroy S, Altshuler LL, Suppes T, et al. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry 2001;158:420-426. PMID: 11229983
  12. Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990 Nov 21;264(19):2511-8. PMID: 2232018
  13. Wu LT, Woody GE, Yang C, Blazer DG. How do prescription opioid users differ from users of heroin or other drugs in psychopathology: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Addict Med 2011;5:28-35. PMID: 21532972
  14. 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
  15. Crump C, Sundquist K, Winkleby MA, Sundquist J. Mental disorders and risk of accidental death. Br J Psychiatry. 2013;203(3):297-302. PMID: 23969485
  16. 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
  17. 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
  18. 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
  19. Goodwin FK, Jamison KR. Manic Depressive Illness In: Bipolar Disorders and Recurrent Depression, 2nd edition. New York: Oxford University Press; 2007.
  20. Akiskal HS. Mood disorders. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan and Sadock’s Comprehensive Textbook of Psychiatry, 10th edition. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2017.
  21. Weiss RD, Mirin SM. Substance abuse as an attempt at self-medication. Psych Med 1987;3:357-67. PMID: 3916681
  22. Busse J, Craigie S, Juurlink D, et al. Guideline for opioid therapy and chronic noncancer pain: Appendix. CMAJ 2017. PMID: 26461074
  23. 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
  24. VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults. 2010. Bipolar Disorder Guidelines 2010
  25. U.S. Department of Veterans Affairs.  VA/DoD clinical practice guideline for opioid therapy for chronic pain. Washington, DC: US Department of Veterans Affairs; 2017. VA/DOD 2017
  26. FDA Drug Safety Communication. FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. August 31, 2016. FDA Drug Safety Communication 2017
  27. Dumas EO, Pollack GM. Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. AAPS J. 2008;10:537-51. PMID: 18989788
  28. White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction 1999;94:961-72. PMID: 10707430
  29. Federation of State Medical Boards (FSMB). Guidelines for the Chronic Use of Opioid Analgesics. April 2017. Federation of State Medical Boards