Phase II Clinical Trial of Atorvastatin in Mild Traumatic Brain Injury.

Statins constitute a class of medications commonly used in the treatment of elevated cholesterol. However, in experimental studies, statins also have other non-cholesterol-mediated mechanisms of action, which may have neuroprotective effects. The aim of this study was to determine whether administration of atorvastatin for 7 days post-injury would improve neurological recovery in patients with mild traumatic brain injury (mTBI). The hypothesis was that atorvastatin administration would reduce post-concussion symptoms and also that atorvastatin administration for 1 week post-injury would be safe. One hundred forty patients with mTBI were planned to be enrolled and randomly assigned to receive atorvastatin 1 mg/kg (up to 80 mg/kg) per day or placebo for 7 days starting within 24 h of injury. Assessments of post-concussion syndrome, post-traumatic stress and depressive symptoms, cognition, memory, verbal fluency, functional, and work status were performed at baseline, 1 week, and 1 and 3 months. The result on the Rivermead Post-Concussion Symptoms Questionnaire at 3 months was the primary outcome. Enrollment in the trial was stopped early because of difficulty in recruiting sufficient numbers of subjects. Fifty-two patients with mTBI were enrolled; 28 patients received atorvastatin and 24 received placebo. The median Rivermead score was 2 for the atorvastatin group, compared to 3.5 for the placebo group, at 3 months post-injury (chi(2) (1) = 0.0976; p = 0.7547). The change in the Rivermead score between baseline and 3 months was also analyzed. The median decrease in score was 4 for the atorvastatin group and 10.5 for the placebo group (chi(2) (1) = 0.8750; p = 0.3496). No serious adverse events occurred, and there was no significant difference in the incidence of adverse events in the two treatment groups. Atorvastatin administration for 7 days post-injury was safe, but there were no significant differences in neurological recovery post-mTBI with atorvastatin.