Botulinum Toxin Type A for the Treatment of Post-traumatic Headache: A Randomized, Placebo-Controlled, Cross-over Study.

Abstract

Botulinum toxin type A (BoNT/A) is an approved treatment for chronic migraine and has been shown to be effective in reducing number, days, and severity of headache in other headache disorders. Whether botulinum toxin is a safe and effective treatment specifically for post-traumatic headache (PTH), however, is unknown. This study sought to determine whether treatment with BoNT/A improved symptoms of PTH in military veterans. Forty subjects with PTH were randomized to receive treatment of either BoNT/A or a saline placebo. Sixteen weeks post-treatment or at return to baseline headache severity, subjects were crossed over to receive treatment with the other medication than previously treated with in the first session. Subjects recorded number of headaches, number of headache days, and headache pain severity in daily diaries. Outcome measures included change in the weekly number of headaches, number of headache days per week, and headache pain severity compared to baseline, and the change in number of headaches and number of headaches days at baseline compared to the rating scores averaged across weeks 6-11. The number of headaches per week significantly decreased by 2.24 (43.3%) with BoNT/A treatment (P < .001) and significantly increased by 1.28 (35.1%) with placebo (P = .02) at the end of the 16 weeks and the difference between groups was also significant (P < .001). The number of headache days per week also significantly decreased by 2.24 (44.4%) at the end of 16 weeks with BoNT/A treatment (P < .001), was not significantly changed with placebo, and the difference between the two groups was significant (P < .001). Both the change in number of headaches and number of headache days averaged across weeks 6-11 compared to baseline were significantly decreased in the BoNT/A group (1.6 and 1.4, respectively) compared to a significant increase of 0.3 in number of weekly headaches and a nonsignificant decrease of 0.1 in number of headache days for the placebo group (P = .048 and P = .005, respectively). Headache pain severity was significantly reduced by 0.06 with botulinum toxin treatment (P = .02) and was not significantly increased by 0.04 in the placebo group with a significant difference between groups (P = .006). Treatment with BoNT/A clinically and significantly improved the frequency and pain severity of PTH compared to placebo in military veterans. Limitations of the study include subject dropout, adherence to documenting variables daily in the dairy, and only one treatment of BoNT/A. Strengths include the cross-over study design, which demonstrated that BoNT/A was effective regardless of treatment order. This dataset is the first prospective study to evaluate BoNT/A as an intervention for symptoms of PTH and provides evidence that larger-scale and multiple treatment studies evaluating BoNT/A for this headache type are warranted.