Zonisamide, a sulfonamide anticonvulsant, demonstrated promising efficacy for the prophylactic treatment of chronic and episodic cluster headache disorders, according to case series study results published in Headache.

The retrospective study enrolled a total of 20 patients with cluster headache, including episodic (n=12) and chronic (n=8), from a private headache clinic in Texas. Only patients who had been or were currently being treated with zonisamide were included in the final analysis. The researchers evaluated the treatment’s efficacy, defined as remission from headache or a >50% reduction in frequency or severity of cluster headache. Investigators also analyzed responder status, adverse events, and dosages.

Related Articles

Approximately 70% of patients (n=14) showed response to zonisamide, with effective plasma concentrations ranging from 10.2 to 31.9 μg/mL. The lack of efficacy resulted in treatment discontinuation in 2 non-responders, whereas 4 non-responders discontinued treatment due to intolerable adverse events. The remaining cohort did not experience any other serious adverse events. While 8 patients experienced weight loss/anorexia, the majority viewed this adverse event as positive. Patients experiencing weight loss were found to have lost a mean of 10.5% of their body weight within 6 months of therapy initiation.

Continue Reading

Study limitations included the small sample size, as well as the inclusion of patients from a single center, which may limit the generalizability of the findings.

The researchers concluded that these preliminary findings, in addition to the low adverse event profile, makes zonisamide a promising choice for cluster headache prophylaxis. They do, however, go on to state that “further research to confirm the utility of zonisamide in the prevention of cluster headache is warranted.”


Limmer AL, Holland LC, Loftus BD, et al. Zonisamide for Cluster Headache Prophylaxis: A Case Series. Headache. 2019;59(6):924-929.

This article originally appeared on Neurology Advisor