Treatment of Persistent Post-Traumatic Headache and Post-Concussion Symptoms Using Repetitive Transcranial Magnetic...

Persistent post-traumatic headache (PTH) after mild traumatic brain injury is one of the most prominent and highly reported persistent post-concussion symptoms (PPCS). Non-pharmacological treatments, including non-invasive neurostimulation technologies, have been proposed for use. Our objective was to evaluate headache characteristics at 1 month after repetitive transcranial magnetic stimulation (rTMS) treatment in participants with PTH and PPCS. A double-blind, randomized, sham-controlled, pilot clinical trial was performed on 20 participants (18-65 years) with persistent PTH (International Classification of Headache Disorders, 3rd edition) and PPCS (International Classification of Diseases, Tenth Revision). Ten sessions of rTMS therapy (10 Hz, 600 pulses, 70% resting motor threshold amplitude) were delivered to the left dorsolateral pre-frontal cortex. The primary outcome was a change in headache frequency or severity at 1 month post-rTMS. Two-week-long daily headache diaries and clinical questionnaires assessing function, PPCS, cognition, quality of life, and mood were completed at baseline, post-treatment, and at 1, 3, and 6 months post-rTMS. A two-way (treatment × time) mixed analyisis of variance indicated a significant overall time effect for average headache severity (F_(3,54) = 3.214; p = 0.03) and a reduction in headache frequency at 1 month post-treatment (#/2 weeks, REAL -5.2 [standard deviation {SD} = 5.8]; SHAM, -3.3 [SD = 7.7]). Secondary outcomes revealed an overall time interaction for headache impact, depression, post-concussion symptoms, and quality of life. There was a significant reduction in depression rating in the REAL group between baseline and 1 month post-treatment, with no change in the SHAM group (Personal Health Questionnaire-9; REAL, -4.3 [SD = 3.7[ p = 0.020]; SHAM, -0.7 [SD = 4.7; p = 1.0]; Bonferroni corrected). In the REAL group, 60% returned to work whereas only 10% returned in the SHAM group (p = 0.027). This pilot study demonstrates an overall time effect on headache severity, functional impact, depression, PPCS, and quality of life after rTMS treatment in participants with persistent PTH; however, findings were below clinical significance thresholds. There was a 100% response rate, no dropouts, and minimal adverse effects, warranting a larger phase II study. Clinicaltrials.gov: NCT03691272.