Co-occurring Depression and Suicidal Ideation in Opioid Use Disorder: Prevalence and Response During Treatment With Buprenorphine-Naloxone and Injection Naltrexone
Objective: The concept of “deaths of despair” (suicide, overdose, and alcohol-related liver disease) highlights the importance of detecting and understanding the course of co-occurring depression in patients with opioid use disorder (OUD).
Methods: In a 24-week trial of 570 patients with DSM-5–defined OUD randomized to buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX) from January 2014 to January 2017, the prevalence of depression (assessed with Hamilton Depression Rating Scale [HDRS]) was examined at baseline and after 4 weeks of treatment, and the association between depression and relapse to opioid use was explored using logistic regression.
Results: Among 473 patients who initiated medication, 14.2% (67/473) had moderate/severe depression (HDRS ≥ 17) and 34.9% (165/473) had mild depression (8 ≤ HDRS ≤ 16) at baseline. Patients with moderate/severe depression had more frequent histories of anxiety disorders and suicidal ideation. After 4 weeks of treatment, approximately two-thirds of participants with depression either responded (HDRS reduced ≥ 50% from baseline) or remitted (HDRS ≤ 7), with no significant differences between medication treatment groups. Those with moderate/severe depression were less likely to remit (52.8%; 28/53) compared to those with mild depression (76%; 98/129) at week 4 (OR = 0.43, 95% CI = 0.21–0.89, P = .02). Further, those who remitted at week 4 had lower, but not significantly different, risk of relapse to opioids compared to those who did not remit (OR = 0.55, 95% CI = 0.28–1.08, P = .08).
Conclusions: Depression is common among patients with OUD and often remits after initiation of BUP-NX or XR-NTX, although when it does not remit it may be associated with worse opioid use outcome. Depression should be screened and followed during initiation of treatment and, when it does not remit, specific depression treatment should be considered.
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Chang HY, Kharrazi H, Bodycombe D, et al. Healthcare costs and utilization associated with high-risk prescription opioid use: a retrospective cohort study. BMC Med. 2018;16(1):69. PubMedCrossRef
Bohnert ASB, Ilgen MA. Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019;380(1):71–79. PubMedCrossRef
Martins SS, Fenton MC, Keyes KM, et al. Mood and anxiety disorders and their association with non-medical prescription opioid use and prescription opioid-use disorder: longitudinal evidence from the National Epidemiologic Study on Alcohol and Related Conditions. Psychol Med. 2012;42(6):1261–1272. PubMedCrossRef
Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry. 2018;75(4):336–346. PubMedCrossRef
Hasin D, Nunes E, Meydan J. Comorbidity of Alcohol, Drug, and Psychiatric Disorders: Epidemiology. CRC Press; 2004.
Oquendo MA, Volkow ND. Suicide: a silent contributor to opioid-overdose deaths. N Engl J Med. 2018;378(17):1567–1569. PubMedCrossRef
Connery HS, Taghian N, Kim J, et al. Suicidal motivations reported by opioid overdose survivors: a cross-sectional study of adults with opioid use disorder. Drug Alcohol Depend. 2019;205:107612. PubMedCrossRef
Case A, Deaton A. Deaths of Despair and the Future of Capitalism. Princeton University Press; 2020.
Pompili M, Rihmer Z, Akiskal H, et al. Temperaments mediate suicide risk and psychopathology among patients with bipolar disorders. Compr Psychiatry. 2012;53(3):280–285. PubMedCrossRef
Brown SA, Inaba RK, Gillin JC, et al. Alcoholism and affective disorder: clinical course of depressive symptoms. Am J Psychiatry. 1995;152(1):45–52. PubMedCrossRef
Strain EC, Stitzer ML, Bigelow GE. Early treatment time course of depressive symptoms in opiate addicts. J Nerv Ment Dis. 1991;179(4):215–221. PubMedCrossRef
Kosten TR, Morgan C, Kosten TA. Depressive symptoms during buprenorphine treatment of opioid abusers. J Subst Abuse Treat. 1990;7(1):51–54. PubMedCrossRef
Mysels DJ, Cheng WY, Nunes EV, et al. The association between naltrexone treatment and symptoms of depression in opioid-dependent patients. Am J Drug Alcohol Abuse. 2011;37(1):22–26. PubMedCrossRef
Brown SA, Schuckit MA. Changes in depression among abstinent alcoholics. J Stud Alcohol. 1988;49(5):412–417. PubMedCrossRef
Weddington WW, Brown BS, Haertzen CA, et al. Changes in mood, craving, and sleep during short-term abstinence reported by male cocaine addicts. A controlled, residential study. Arch Gen Psychiatry. 1990;47(9):861–868. PubMedCrossRef
Liappas J, Paparrigopoulos T, Tzavellas E, et al. Impact of alcohol detoxification on anxiety and depressive symptoms. Drug Alcohol Depend. 2002;68(2):215–220. PubMedCrossRef
Krupitsky E, Zvartau E, Blokhina E, et al. Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant. Am J Drug Alcohol Abuse. 2016;42(5):614–620. PubMedCrossRef
Latif ZE, Šaltyte Benth J, Solli KK, et al. Anxiety, depression, and insomnia among adults with opioid dependence treated with extended-release naltrexone vs buprenorphine-naloxone: a randomized clinical trial and follow-up study. JAMA Psychiatry. 2019;76(2):127–134. PubMedCrossRef
Nunes EV, Quitkin FM, Donovan SJ, et al. Imipramine treatment of opiate-dependent patients with depressive disorders. a placebo-controlled trial. Arch Gen Psychiatry. 1998;55(2):153–160. PubMedCrossRef
Titievsky J, Seco G, Barranco M, et al. Doxepin as adjunctive therapy for depressed methadone maintenance patients: a double-blind study. J Clin Psychiatry. 1982;43(11):454–456. PubMed
Woody GE, O’Brien CP, Rickels K. Depression and anxiety in heroin addicts: a placebo-controlled study of doxepin in combination with methadone. Am J Psychiatry. 1975;132(4):447–450. PubMedCrossRef
Nunes EV, Sullivan MA, Levin FR. Treatment of depression in patients with opiate dependence. Biol Psychiatry. 2004;56(10):793–802. PubMedCrossRef
Rounsaville BJ, Weissman MM, Crits-Christoph K, et al. Diagnosis and symptoms of depression in opiate addicts. course and relationship to treatment outcome. Arch Gen Psychiatry. 1982;39(2):151–156. PubMedCrossRef
Rounsaville BJ, Kosten TR, Weissman MM, et al. Prognostic significance of psychopathology in treated opiate addicts. a 2.5-year follow-up study. Arch Gen Psychiatry. 1986;43(8):739–745. PubMedCrossRef
Dreifuss JA, Griffin ML, Frost K, et al. Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study. Drug Alcohol Depend. 2013;131(1-2):112–118. PubMedCrossRef
Lee JD, Nunes EV Jr, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309–318. PubMedCrossRef
Lee JD, Nunes EV, Mpa PN, et al. NIDA Clinical Trials Network CTN-0051, extended-release naltrexone vs buprenorphine for opioid treatment (X:BOT): study design and rationale. Contemp Clin Trials. 2016;50:253–264. PubMedCrossRef
Nunes EV, Lee JD, Sisti D, et al. Ethical and clinical safety considerations in the design of an effectiveness trial: a comparison of buprenorphine versus naltrexone treatment for opioid dependence. Contemp Clin Trials. 2016;51:34–43. PubMedCrossRef
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. PubMedCrossRef
Zimmerman M, Martinez JH, Young D, et al. Severity classification on the Hamilton Depression Rating Scale. J Affect Disord. 2013;150(2):384–388. PubMedCrossRef
Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991;48(9):851–855. PubMedCrossRef
Cusin C, Yang H, Yeung A, et al. Rating Scales for Depression. Humana Press; 2009.
Lee JD, McDonald R, Grossman E, et al. Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial. Addiction. 2015;110(6):1008–1014. PubMedCrossRef
Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506–1513. PubMedCrossRef
Nunes EV, Bisaga A, Krupitsky E, et al. Opioid use and dropout from extended-release naltrexone in a controlled trial: implications for mechanism. Addiction. 2020;115(2):239–246. PubMedCrossRef
Hser YI, Saxon AJ, Huang D, et al. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction. 2014;109(1):79–87. PubMedCrossRef
Sobell L, Sobell M. Alcohol Timeline Followback Users’ Manual. Addiction Research Foundation; 1995.
Bodkin JA, Zornberg GL, Lukas SE, et al. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995;15(1):49–57. PubMedCrossRef
Ling W, Hillhouse MP, Saxon AJ, et al. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Addiction. 2016;111(8):1416–1427. PubMedCrossRef
Aharonovich E, Liu X, Nunes E, et al. Suicide attempts in substance abusers: effects of major depression in relation to substance use disorders. Am J Psychiatry. 2002;159(9):1600–1602. PubMedCrossRef
Hasin D, Liu X, Nunes E, et al. Effects of major depression on remission and relapse of substance dependence. Arch Gen Psychiatry. 2002;59(4):375–380. PubMedCrossRef
Dixit AR, Crum RM. Prospective study of depression and the risk of heavy alcohol use in women. Am J Psychiatry. 2000;157(5):751–758. PubMedCrossRef
Carroll KM, Power ME, Bryant K, et al. One-year follow-up status of treatment-seeking cocaine abusers: psychopathology and dependence severity as predictors of outcome. J Nerv Ment Dis. 1993;181(2):71–79. PubMedCrossRef
Holt LJ, O’Malley SS, Rounsaville BJ, et al. Depressive symptoms, drinking consequences, and motivation to change in first time DWI offenders. Am J Drug Alcohol Abuse. 2009;35(3):117–122. PubMedCrossRef
Curran GM, Flynn HA, Kirchner J, et al. Depression after alcohol treatment as a risk factor for relapse among male veterans. J Subst Abuse Treat. 2000;19(3):259–265. PubMedCrossRef