A Pilot Randomized Controlled Trial of Prophylactic Medications for Chronic Post-Traumatic Headaches in U.S. Army Soldiers (P03.226)

Objective: To evaluate the tolerability and efficacy of amitriptyline, propranolol, and topiramate for chronic post-traumatic headaches (PTH) in military personnel. Background Chronic headaches are a common symptom after concussion but medical management is limited by a lack of clinical trials. Design/Methods: A single-center, randomized, double-blinded, placebo-controlled trial was conducted with U.S. Army soldiers fulfilling ICHD-2 criteria for chronic PTH. Subjects were randomized to placebo, propranolol 80 mg, amitriptyline 50 mg, or topiramate 100 mg for 3 months. The primary outcome measure was the number of days per month with moderate or severe headache. Secondary outcomes included the MIDAS and PTSD symptom checklist. Results: 305 soldiers were screened for eligibility, 64 were enrolled, 39 completed drug titration, and 34 completed treatment. Study discontinuation rates ranged from 39% for topiramate to 53% for amitriptyline but were not significantly different between arms. Monthly headache days decreased from 12.2 at baseline to 7.9 during the final month in all subjects (-36%, p=0.0001), 16.7 to 8.7 in the placebo arm (-48%, p=0.012), 11.7 to 6.1 in the amitriptyline arm (-41%, p=0.0005), 14.0 to 8.3 in the propranolol arm (-41%, p=0.10), and 9.3 to 8.8 in the topiramate arm (-5%, p=0.80). Responder rates were 49% (19/39) for all subjects, 50% (3/6) for placebo, 67% (8/12) for amitriptyline, 44% (4/9) for propranolol, and 33% (4/12) for topiramate. Mean MIDAS scores significantly declined in the placebo, topiramate, and propranolol arms. PTSD symptoms significantly improved in the topiramate arm only. Conclusions: This pilot trial is limited by small sample size and high responsivity in the placebo arm. Amitriptyline, propranolol, and topiramate were similarly tolerated and associated with significant improvements in headache frequency and/or headache-related disability but no treatment was superior to placebo. Topiramate was the only treatment that improved PTSD symptoms. These findings will be useful for designing large multi-center clinical trials. Supported by: DOD TBI Research Program grant number PT074428 and Comprehensive National Neuroscience Program. Disclosure: Dr. Erickson has received research support from Merck & Co., Inc.