Safety and feasibility of minocycline in treatment of acute traumatic brain injury

Background: Minocycline is a pleomorphic neuroprotective agent well studied in animal models of traumatic brain injury (TBI) and brain ischemia. Methods: To test the hypothesis that administration of minocycline in moderate to severe TBI (Glasgow Coma Score 3-12). Fifteen patients were enrolled in a two-dose escalation study of minocycline to evaluate the safety of twice the recommended antibiotic dosage; tier 1 n = 7 at a loading dose of 800 mg followed by 200 mg twice a day (BID) for 7 days; tier 2 n = 8 at a loading dose of 800 mg followed by 400 mg BID for 7 days. Results: The mean initial GCS was 5.6 for Tier 1 patients and 5.4 for Tier 2. The Disability Rating Scale (DRS) had a trend towards improvement with the higher dose 12.5 SD +/- 7.7 (N = 5) for Tier 1 at 4 weeks and 8.5 SD +/- 9.9 at week 12 (N = 5), whereas for Tier 2 it was 9.7 +/- 6.9 (N = 6) for week 4 and 6.0 SD +/- 6.1 (N = 7) for week 12 (p = .251 repeated measures ANOVA). Liver function tests increased but resolved after the first week and there were no infections. Conclusions: Minocycline was safe for moderate to severe TBI at a dose twice that as recommended for treatment of infection. The higher dose did trend towards an improved outcome.