What question did this study set out to answer?

This review aims to evaluate the effectiveness of buprenorphine compared to other medications for opioid use disorder in adults with co-occurring depression.

June 14, 2026Open Access

Efficacy of buprenorphine in the treatment of co- occurring opioid use disorder and depression: a systematic review and exploratory meta-analysis

Key Points

This review aims to evaluate the effectiveness of buprenorphine compared to other medications for opioid use disorder in adults with co-occurring depression.
Conducted a systematic review of randomized and observational studies from 2000 to 2025 using multi-database searches and PRISMA guidelines.
Included studies involved adults with opioid use disorder and depressive symptoms receiving buprenorphine as treatment.
Compared outcomes of buprenorphine against methadone and extended-release naltrexone for depressive symptoms, treatment retention, and illicit opioid use.
Depressive symptoms improved across treatment groups, but differences between buprenorphine and comparators were inconsistent.
Four randomized trials indicated no significant difference between buprenorphine and methadone.
Buprenorphine/naloxone and XR-NTX showed parallel improvements in one randomized controlled trial.

Abstract

Background: Opioid use disorder (OUD) is frequently linked to clinically significant depressive symptoms, which negatively affect treatment retention, relapse risk, and overdose vulnerability. Beyond its known use in treating OUD, buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist, has been suggested to exert antidepressant benefits, yet evidence in patients with comorbid depression and OUD remains inconsistent. This systematic review examined the comparative effects of buprenorphine versus other medications for opioid use disorder (MOUDs) in adults with OUD and co-occurring depression on depressive symptoms and opioid-use–related outcomes. Methods: Randomised and observational studies published between 2000 and 2025 were identified using a multi-database search (MEDLINE, Embase, CENTRAL, and PsycINFO) and gray-literature screening in accordance with PRISMA 2020 and a pre-registered protocol. Eligible studies enrolled adults with OUD and co-occurring depressive symptoms receiving therapeutic-dose buprenorphine as the intervention. Methadone and extended-release naltrexone (XR-NTX) served as comparators. The primary outcomes were depressive symptoms, treatment retention, and illicit opioid use. RoB-2 and ROBINS-I were used to evaluate the risk of bias, and GRADE to evaluate the certainty of the evidence. Meta-analysis was performed only exploratorily due to substantial heterogeneity. Results: Six studies (five RCTs and one observational study) met the inclusion criteria. Depressive symptoms improved substantially in all treatment groups, but the between-group differences were inconsistent. Four randomised trials showed no significant difference between buprenorphine and methadone. One long-term trial and one observational study favored buprenorphine. Buprenorphine/naloxone and XR-NTX showed parallel improvements in one RCT. All studies produced comparable OUD outcomes. Certainty of evidence was low to very low for all primary outcomes. Conclusion: Stabilisation on an MOUD, whether buprenorphine, methadone, or XR-NTX, is linked to clinically meaningful reductions in depressive symptoms, illicit opioid use, and improved treatment retention. Buprenorphine does not consistently outperform other MOUDs according to available evidence.

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