A meta-analysis of the potential antidepressant effects of buprenorphine versus placebo as an adjunctive pharmacotherapy for treatment-resistant depression

Background: Numerous reports have suggested that buprenorphine may have antidepressant effects. Many individuals with depressive disorders don't respond to first-line treatment and are classified with treatment-resistant depression (TRD). Novel therapies for depression are required to better treat this population. This meta-analysis of randomized placebo-controlled trials sought to evaluate the potential antidepressant effects of buprenorphine as an adjunctive pharmacological treatment for individuals with TRD. Methods: PubMed, Embase, CINAHL, Web of Science, and ClinicalTrials.gov databases were searched until June 2019 for original peer-reviewed reports of buprenorphine used for the treatment of depression. Standardized mean differences (SMD) were generated from random effects models. Risk of publication bias was assessed using a funnel plot. Potential sources of heterogeneity were explored in subgroup analyses. Results: In six studies that met inclusion criteria, depression symptom severity in individuals with TRD was not significantly decreased after an adjunctive intervention with buprenorphine when compared to placebo (SMD = -0.07, 95% CI: -0.21-0.06, p = 0.30). Five of the six studies utilized a combination of buprenorphine/samidorphan. In these studies, depression symptom severity was also not significantly reduced after intervention compared to placebo (SMD = -0.08, 95% CI: -0.21 - 0.05, p = 0.23). Limitations: Five included studies were performed by the same research group with significant conflicts of interest. Conclusions: This meta-analysis did not reveal a significant reduction in depression symptom severity in individuals with TRD after an adjunctive intervention with buprenorphine when compared to placebo. However, more optimal doses of buprenorphine (2 mg/day) and longer treatment lengths should be explored.