The efficacy and safety of buprenorphine for the treatment of depression: A systematic review and meta-analysis

Background: Depressive disorders are common. Many patients with major depression do not achieve remission with available treatments. Buprenorphine has been raised as a potential treatment for depression as well as suicidal behavior but may pose certain risks.Methods: A meta-analysis comparing the efficacy, tolerability, and safety of buprenorphine (or combinations such as buprenorphine/samidorphan) versus control in improving symptoms in patients with depression. Medline, Cochrane Database, PsycINFO, Excerpta Medica Database and The Cumulative Index to Nursing and Allied Health Literature were searched from inception through January 2, 2022. Depressive symptoms were pooled using Hedge's g with 95% Confidence Intervals (CI). Tolerability, safety, suicide outcomes were summarized qualitatively.Results: 11 studies (N = 1699) met inclusion criteria. Buprenorphine had a small effect on depressive symptoms (Hedges' g 0.17, 95%CI: 0.05-0.29). Results were driven by six trials of buprenorphine/samidorphan (N = 1,343, Hedges's g 0.17, 95%CI: 0.04-0.29). One study reported significant improvement in suicidal thoughts (Least Squares Mean Change:-7.1, 95%CI:-12.0 - 2.3). Most studies found buprenorphine was well-tolerated with no evidence of abuse behavior or dependency.Conclusions: Buprenorphine may have a small benefit for depressive symptoms. Future research should clarify the dose response relationship between buprenorphine and depression.