Zonisamide for Cluster Headache Prophylaxis: A Case Series

There is very little literature surrounding the prophylactic use of zonisamide in cluster headaches. The study aims to evaluate the effectiveness of zonisamide for prophylaxis of cluster headache in patients with chronic or episodic cluster headache.

Both chronic and episodic cluster headaches are debilitating disorders which are often refractory to multiple prophylactic medication regimens. There is a scarcity of research in this area, and current prophylactic options for patients are fairly limited, which is troublesome for affected patients. Zonisamide is an established antiepileptic with a multifactorial mechanism of action which has shown to be useful in other headache disorders such as migraine.

Twenty cluster headache patients, both episodic (n = 12; ICHD 3.1.1) and chronic (n = 8; ICHD 3.1.2), who had been or currently were treated with zonisamide, were retrospectively evaluated. Effectiveness of the medication was assessed and identified as headache remission or a reduction in severity or frequency of cluster headache of greater than 50%. Responder status, side effects, and dosage were recorded.

Fourteen (70%) patients responded to zonisamide treatment, while 6 (30%) did not. Recorded effective plasma zonisamide levels ranged from 10.2 to 31.9 μg/mL. Of the 6 non-responders, 2 stopped the medication due to ineffectiveness, while 4 discontinued the medication secondary to intolerable side effects ranging from gastrointestinal upset to malaise. No more serious adverse events occurred. Eight patients total experienced weight loss/anorexia which many perceived as a positive effect; they lost an average of 10.5% of their body weight in the first 6 months of therapy.

Zonisamide appears to be an effective prophylactic treatment for patients with chronic and episodic cluster headache disorders. Further research in this area is clearly warranted.