Systematic review and meta-analysis of the efficacy and safety of minocycline in schizophrenia

Objective. Our aim was to perform an updated systematic review and meta-analysis on the efficacy and safety of adjunctive minocycline as a treatment of schizophrenia. Methods. We conducted a PubMed/Scopus database search from inception to 3 February 2016 for randomized, placebo-controlled trials (RCTs), open non-randomized studies, and case reports/series evaluating minocycline in patients with schizophrenia. Random-effects meta-analysis of positive, negative, depressive, and cognitive symptom rating scales, discontinuation and adverse effects rates calculating standardized mean difference (SMD), and risk ratios95% confidence intervals (CI95%) were calculated. Results. Six RCTs were eligible (minocycline n=215, placebo n=198) that demonstrated minocycline's superiority versus placebo for reducing endpoint Positive and Negative Syndrome Scale (PANSS) total scores (SMD=-0.59; CI95%=[1.15, -0.03]; p=0.04), negative (SMD=-0.76; CI95%=[-1.21, -0.31]; p=0.001); general subscale scores (SMD=-0.44; CI95%=[-0.88, -0.00]; p=0.05), Clinical Global Impressions scores (SMD=-0.50; CI95%=[-0.78, -0.22]; p<0.001); and executive functioning (SMD=0.22; CI95%=[0.01, 0.44]; p=0.04). Endpoint PANSS positive symptom scores (p=0.13), depression rating scale scores (p=0.43), attention (p=0.47), memory (p=0.52), and motor speed processing (p=0.50) did not significantly differ from placebo, before execution of a trim-and-fill procedure. Minocycline did not differ compared to placebo on all-cause discontinuation (p=0.56), discontinuation due to inefficacy (p=0.99), and intolerability (p=0.51), and due to death (p=0.32). Data from one open-label study (N=22) and three case series (N=6) were consistent with the metaanalytic results. Conclusions. Minocycline appears to be an effective adjunctive treatment option in schizophrenia, improving multiple relevant disease dimensions. Moreover, minocycline has an acceptable safety and tolerability profile. However, more methodologically sound and larger RCTs remain necessary to confirm and extend these results.