ABSTRACT
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.
Trial Registration: ClinicalTrials.gov identifier: NCT02032433
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References (45)
- 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. PubMed CrossRef
- Bohnert ASB, Ilgen MA. Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019;380(1):71–79. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- Kosten TR, Morgan C, Kosten TA. Depressive symptoms during buprenorphine treatment of opioid abusers. J Subst Abuse Treat. 1990;7(1):51–54. PubMed CrossRef
- 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. PubMed CrossRef
- Brown SA, Schuckit MA. Changes in depression among abstinent alcoholics. J Stud Alcohol. 1988;49(5):412–417. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- Nunes EV, Sullivan MA, Levin FR. Treatment of depression in patients with opiate dependence. Biol Psychiatry. 2004;56(10):793–802. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. PubMed CrossRef
- Zimmerman M, Martinez JH, Young D, et al. Severity classification on the Hamilton Depression Rating Scale. J Affect Disord. 2013;150(2):384–388. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
- 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. PubMed CrossRef
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