Adjunctive minocycline for major mental disorders: A systematic review.

Abstract

OBJECTIVES:

This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD).

METHODS:

A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias.

RESULTS:

Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95%CI: -0.73, -0.16), p=0.002; I2=77%], positive [SMD: -0.15 (95%CI: -0.28, -0.02), p=0.02; I2=0%], negative [SMD: -0.62 (95%CI: -0.95, -0.28), p=0.0003; I2=85%] and general psychopathology scores [SMD: -0.28 (95%CI: -0.53, -0.03), p=0.03; I2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95%CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category.

CONCLUSION:

In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated.

REVIEW REGISTRATION:

PROSPERO: CRD42018102483.

• Authors: Wei Zheng, Xiao-Min Zhu, Qing-E Zhang, Gen Cheng, Dong-Bin Cai, Jie He, Chee H Ng, Gabor S Ungvari, Xiao-Jiang Peng, Yu-Ping Ning, Yu-Tao Xiang
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 33 Issue 10 Pg. 1215-1226 (10 2019) ISSN: 1461-7285 [Electronic] United States
• PMID: 31294649 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Systematic Review)

Chemical References

• Anti-Inflammatory Agents
• Minocycline

Topics

• Anti-Inflammatory Agents (adverse effects, pharmacology)
• Bipolar Disorder (drug therapy)
• Depressive Disorder, Major (drug therapy)
• Humans
• Minocycline (adverse effects, pharmacology)
• Schizophrenia (drug therapy)