Minocycline in acute stroke

Background: Minocycline has emerged as a potential adjunctive neuroprotective therapy in acute stroke owing to its anti-inflammatory, antiapoptotic, and blood–brain barrier-stabilizing effects. We aimed to evaluate the efficacy and selected safety-related outcomes of minocycline in acute stroke, including ischemic and hemorrhagic subtypes. Methods: This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Major databases were searched through March 20, 2026 for randomized controlled trials comparing minocycline with control or standard care in acute stroke. Risk ratios (RRs) and mean differences were pooled with 95% confidence intervals (CIs). Risk of bias was assessed using ROB 2, certainty of evidence using Grading of Recommendations Assessment, Development, and Evaluation, and robustness using trial sequential analysis. Results: Nine trials including 2186 participants were analyzed. Minocycline significantly reduced 3-month National Institutes of Health Stroke Scale scores in acute ischemic stroke (mean difference −2.43, 95% CI −4.42–−0.44; P = .0169), but not in intracerebral hemorrhage. Functional independence at 3 months showed a favorable signal in ischemic stroke (modified rankin scale 0 to 2: risk ratio 1.40, 95% CI 1.05–1.86; P = .0219), while favorable outcome defined as modified rankin scale 0 to 1 was not significantly improved. Barthel Index also favored minocycline in ischemic stroke, although overall results were not statistically significant. Mortality, recurrent vascular events, hemorrhagic transformation, hematoma volume, perihematomal edema, and Matrix Metalloproteinase-9levels were not significantly altered. Trial sequential analysis indicated insufficient evidence for definitive conclusions. Conclusion: Minocycline may improve neurological recovery in acute ischemic stroke; however, these findings remain exploratory because of substantial heterogeneity, low-certainty evidence, and inconclusive trial sequential analysis. Larger standardized trials are required.