Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: A systematic review and meta-analysis of randomized controlled trials

Objective: This study aimed to perform a comprehensive meta-analysis of minocycline augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Methods: Data published up to 2 June 2014 were obtained from the PubMed, PsycINFO, Google Scholar, and Cochrane Library databases. We conducted a systematic review and meta-analysis of patient data from randomized controlled trials (RCTs) comparing minocycline with placebo. Relative risk (RR), standardized mean difference (SMD), and 95% confidence intervals were calculated. Results: We included four RCTs. The total sample included 330 patients. Minocycline was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD = -0.70), PANSS negative subscale scores (SMD = -0.86), and PANSS general subscale scores (SMD = -0.50) but was not different from placebo for PANSS positive subscale scores (SMD = -0.26) and depressive symptoms (SMD = -0.28). Minocycline was equivalent to placebo for all-cause discontinuation (RR = 1.10), discontinuation due to inefficacy (RR = 0.42), discontinuation due to adverse events (RR = 1.56), and discontinuation due to death (RR = 3.18). Minocycline was superior to placebo for extrapyramidal side-effect scores (SMD = -0.32). Conclusions: Minocycline may improve the psychopathology of schizophrenia, especially the negative symptoms, and seems to be well tolerated.