Minocycline for neuroprotection in stroke and cerebral ischemia: a systematic review and meta-analysis

Stroke remains a leading cause of mortality and long-term disability worldwide, with substantial socioeconomic and healthcare burdens. Minocycline, a tetracycline antibiotic with anti-inflammatory and antioxidant properties and the ability to cross the blood-brain barrier, has emerged as a potential neuroprotective agent in acute ischemic stroke (AIS). However, clinical evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of minocycline in patients with AIS.

We systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library from inception to February 2026 for randomized controlled trials (RCTs) evaluating minocycline in adults with AIS. The primary outcomes were functional outcomes assessed using the modified Rankin Scale (mRS) and neurological outcomes assessed using the National Institutes of Health Stroke Scale. Dichotomous outcomes were pooled as risk ratios (RRs), while continuous outcomes were synthesized as mean differences (MDs), each with 95% confidence intervals (CIs), using random-effects meta-analysis with restricted maximum likelihood estimation. The Hartung-Knapp-Sidik-Jonkman adjustment was applied.

Seven RCTs comprising 2,242 patients (1,113 receiving minocycline and 1,129 receiving placebo) were included. Minocycline was not associated with a statistically significant difference in continuous mRS scores at 90 days (MD = - 0.88; 95% CI: -4.03 to 2.28; p = 0.18; I² = 53.2%). Similarly, minocycline did not significantly improve excellent functional outcome (mRS 0-1) (RR = 1.09; 95% CI: 0.95-1.26; p = 0.14; I² = 0%) or functional independence (mRS 0-2) (RR = 1.05; 95% CI: 0.69-1.59; p = 0.76; I² = 65.2%). Similarly, minocycline was not associated with a statistically significant reduction in NIHSS scores at 90 days (MD = - 2.52; 95% CI: -5.37 to 0.33; p = 0.06) or improvement in BI scores (MD = 8.13; 95% CI: -29.32 to 45.58; p = 0.22). No significant differences were found in stroke recurrence (RR = 1.07; 95% CI: 0.70-1.61; p = 0.58) or mortality (RR = 0.69; 95% CI: 0.40-1.20; p = 0.12).

Minocycline did not demonstrate a statistically significant improvement in functional or neurological outcomes at 90 days compared with the control group. The available evidence suggests no significant increase in stroke recurrence or mortality. Further large-scale, high-quality RCTs are warranted to clarify the potential neuroprotective effects of minocycline and determine its role in the routine management of AIS.