Adjunctive Minocycline in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled...

Acute ischemic stroke (AIS) is a leading cause of mortality and long-term disability worldwide. Despite advances in acute stroke management, many patients continue to experience substantial neurological disability and incomplete recovery. Minocycline, a tetracycline antibiotic with anti-inflammatory and neuroprotective properties and good blood-brain barrier penetration, has been investigated as a potential adjunctive therapy in AIS.

A systematic search of major databases was conducted identifying randomized controlled trials evaluating minocycline in patients with AIS. Outcomes included functional and neurological recovery assessed using the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel index (BI), as well as mortality and vascular events. Pooled effect estimates were calculated using random-effects meta-analysis.

Seven RCTs comprising 2197 patients were included, with 1093 receiving minocycline and 1104 receiving placebo or standard care. Functional independence at 3 months (mRS 0-2) showed no significant difference between groups (RR 1.28, 95% CI 0.97-1.69; I² = 84.9%). Minocycline was associated with lower NIHSS scores (MD -2.45, 95% CI -4.32 to -0.59; I² = 88.6%) and higher BI scores (MD 12.52, 95% CI 6.28-18.76; I² = 47.0%). Mortality (RR 0.66, 95% CI 0.39-1.090 and stroke recurrence or MI showed no significant differences (RR 0.97, 95% CI 0.69-1.37).

Although a consistent improvement in functional independence was not demonstrated, minocycline showed signals of benefit in selected neurological outcomes with a favorable safety profile. These findings support the need for adequately powered, multicenter randomized trials to clarify its therapeutic role.