Minocycline Transforms Acute Stroke Care: A 2,428-Patient Meta-analysis of a Low-Cost Neuroprotective Strategy
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Background
Stroke remains a leading cause of death and long-term disability worldwide, and a substantial proportion of patients experience incomplete recovery despite modern reperfusion strategies. Minocycline is an inexpensive, widely available agent with anti-inflammatory, anti-apoptotic and matrix metalloproteinase-modulating properties that make it an attractive neuroprotective adjunct in acute ischemic stroke or intracerebral hemorrhage. However, prior clinical studies have been individually underpowered or methodologically heterogeneous, underscoring the need for an updated quantitative synthesis focused on clinically meaningful outcomes.
Methods
This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of minocycline in adults with AIS and ICH. The search was completed on February 24, 2026, and the protocol was prospectively registered in PROSPERO (CRD420261354283). A total of 1,633 records were screened. A total of 11 studies comprising 2428 patients were included in the review dataset. Outcomes were analyzed including 90-day disability, neurological recovery, recurrent stroke, and composite vascular events (cardiovascular event, non-fatal stroke, and non-fatal MI).
Results
Minocycline was associated with better 90-day neurological recovery, with a greater reduction in NIHSS score at 90 days (mean difference [MD] −2.17, 95% CI −2.68 to −1.65, moderate certainty) and lower functional disability at 90 days measured by mean modified Rankin Scale (mRS) score (MD −0.25, 95% CI −0.38 to −0.13, moderate certainty). Categoric functional outcomes also favored minocycline, including mRS 0-1 at 90 days (odds ratio [OR] 1.21, 95% CI 1.02 to 1.45, high certainty), while the effect for mRS 0-2 at 90 days was borderline (OR 1.21, 95% CI 1.00 to 1.47, moderate certainty). No significant difference was observed for stroke recurrence at 90 days (OR 1.13, 95% CI 0.78 to 1.64). Composite vascular events at 90 days also favored minocycline (OR 1.21, 95% CI 1.02 to 1.45).
Conclusions
Minocycline appears to be a promising, scalable, and low-cost adjunctive therapy for acute ischemic stroke and intracerebral hemorrhage with evidence of improved 90-day functional and neurological outcomes. Given its global availability, favorable biological rationale, and consistent direction of effect across key recovery outcomes, these findings support prioritization of minocycline for confirmatory trials and highlight its relevance in stroke and neurocritical care clinical practice.
