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.