Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

Yue Shen; Yi-Fang He; Qiu-Jin Guo; Ming-Hui Deng; Wei-Xia Li; Ren-Rong Wu; Hua-Lin Cai

doi:10.1016/j.psychres.2026.117399

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Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

Yue Shen·Yi-Fang He·Qiu-Jin Guo·Ming-Hui Deng·Wei-Xia Li·Ren-Rong Wu·Hua-Lin Cai

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Abstract

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

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Humans Minocycline Schizophrenia Antipsychotic Agents Outcome Assessment, Health Care Drug Therapy, Combination Adjunctive therapy Cognitive function Meta-analysis Negative symptoms Journal Article Systematic Review Meta-Analysis Review

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Yue Shen, Yi-Fang He, Qiu-Jin Guo, Ming-Hui Deng, Wei-Xia Li, Ren-Rong Wu, Hua-Lin Cai. 2026-08-17. Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.. https://doi.org/10.1016/j.psychres.2026.117399

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Antipsychotic Agents subject Drug Therapy, Combination subject Humans subject Journal Article subject Journal Article; Systematic Review; Meta-Analysis; Review resource Meta-Analysis subject Outcome Assessment, Health Care subject Systematic reviews study

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