Level 2: Mid-level evidence

The efficacy of minocycline (Minocin) following acute ischemic stroke was evaluated in an open-label randomized trial (Neurology. 2007;69:1404-1410). Patients (N=152) with acute stroke, i.e., within the previous 6-24 hours, were randomized to minocycline 200 mg/day vs. placebo orally for five days and followed for 90 days. One patient was excluded due to intracerebral hemorrhage before receiving treatment; 151 patients were analyzed. The NIH Stroke Scale (NIHSS) score was evaluated by a blinded assessor, and findings were categorized as complete or nearly complete improvement (0-1), mild impairment (2-7), moderate impairment (8-14), or severe impairment (≥15).

Comparing minocycline vs. placebo, mean NIHSS scores were 7.5 vs. 7.6 on admission, 6.5 vs. 8.1 at day 7, 1.8 vs. 7.1 at day 30, and 1.6 vs. 6.5 at day 90. The estimated proportion of patients with NIHSS score 0-1 was 0 vs. 0 on admission, 45% vs. 4% at day 7, 50% vs. 6% at day 30, and 55% vs. 5% at day 90. A similar pattern (with greater improvement in minocycline group at 7, 30, and 90 days) was reported using both the Barthel Index and the modified Rankin scale.

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The mechanism of action of minocycline in human stroke is unknown; suggested explanations include the drug’s anti-inflammatory action or its effect on microglial activity, nitric oxide production, and/or inhibition of apoptotic cell death.