Mexiletine for Refractory Chronic Daily Headache: A Report of Nine Cases


  • Conflict of Interest: Dr. Marmura and Mr. Passero have no conflicts of interest. Dr. Young is on the speakers bureaus of Allergan, GlaxoSmithKline, Merck, Ortho-McNeil, and Valeant; serves on the advisory boards of Merck and Ortho-McNeil; and has received research support from AGA Medical, Advanced Bionics, Advanced Neuromodulation Systems, Allergan, Capnia, Eli Lilly, Endo, GlaxoSmithKline, Medtronic, Merck, Minister, and Valeant.

M. Marmura, Department of Neurology, Thomas Jefferson University, 111 S. 11th St. Suite 8130, Philadelphia, PA 19107, USA.


Objective.— To describe the use of mexiletine in the treatment of chronic daily headache in a refractory headache population.

Background.— Intravenous lidocaine is a novel treatment for chronic daily headache with medication overuse and SUNCT syndrome. Mexiletine is a similar but orally active anti-arrhythmic that has been demonstrated to be an effective analgesic in various types of neuropathic pain. We looked at mexiletine as a preventative treatment for headache in refractory patients.

Methods.— We reviewed the medical records of all patients with an order for mexiletine. For each patient, we determined diagnosis, presence of medication overuse on initial evaluation, pain scores, and if the patient received intravenous lidocaine before starting the medication. We then contacted patients by phone to confirm their dose, to review side effects and current pain scores, and to obtain a global impression of effectiveness.

Results.— We identified 9 patients with a chronic daily headache, including chronic migraine or new daily persistent headache, with significant clinical improvement while using mexiletine as a headache preventative. Each patient had failed to respond to multiple preventative and acute treatments. Seven of the 9 rated mexiletine “much more effective” and 2 “more effective” than previous preventative headache medications. The daily dose ranged from 600 mg/day to 1500 mg/day. Side effects were common and occurred in 7 patients. The majority of patients with an order for mexiletine did not respond to treatment or had intolerable side effects.

Discussion.— The preliminary study suggests mexiletine is a useful preventative treatment for some patients with chronic daily headache, including refractory patients with medication overuse or those who have failed multiple preventatives in the past.