Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials

Background: Minocycline has been identified as a potential novel treatment for depression. The objective of the current review is to determine the overall antidepressant efficacy and tolerability of minocycline. Methods: Completed and ongoing clinical trials of minocycline for depression (both bipolar and unipolar) published prior to September 12, 2017 were identified through searching relevant databases. Using a random-effects model, data from randomized controlled trials (RCTs) were pooled to determine the antidepressant effect size of minocycline compared to placebo. Relative risk of all-cause discontinuation was determined to assess overall tolerability. Results: Eighteen clinical studies (including published and unpublished RCTs, open label studies, ongoing clinical trials and a case report) were identified for inclusion in the qualitative synthesis. Only three RCTs (n = 158) met inclusion criteria for quantitative synthesis. The overall antidepressant effect size of minocycline compared to placebo was - 0.78 [95% confidence interval - 0.4 to - 1.33 (P = 0.005)], indicative of a large and statistically significant antidepressant effect. Heterogeneity of the pooled sample was moderate (I-2 = 62%). There was no statistically significant difference in reported adverse effects or all-cause discontinuation in the minocycline group compared to placebo (p = 0.16). Limitations: The small number of published RCTs, small sample sizes, heterogeneity of included studies, and potential publication bias were significant limitations. Conclusions: Overall, a large antidepressant effect was observed for minocycline compared to placebo with good tolerability. The current analysis provides a proof-of-concept for the antidepressant effects of minocycline and provides impetus for future larger RCTs as well as identification of subgroups more likely to benefit from this intervention.