Zonisamide for Cluster Headache Prophylaxis: A Case Series

Abstract

Objective 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. Background 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. Methods 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. Results 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. Conclusions 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.

Current Drug Development Overview: Targeting Voltage-Gated Calcium Channels for the Treatment of Pain

“…Ethosuximide showed limited efficacy when compared to zonisamide (sulfonamide anticonvulsant agent with Cav3.x blocker properties [150,151]), in neuropathic mechanical hypersensitivity [152]. Zonisamide has been shown to reduce pain behavior in several pain models [153,154] and this compound was also effective to treat severe and intractable central poststroke pain in two patients [155], migraine [156][157][158][159], and painful diabetic neuropathy [160]. ABT 639 is also a sulfonamide and nonselective Cav3 antagonist that can produce antinociception when administered intraperitoneally in murine models of neuropathic but not inflammatory pain [161,162], or intrathecally in an inflammatory bowel disease model [163].…”

Pre-Clinical Assessment of the Nose-to-Brain Delivery of Zonisamide After Intranasal Administration

“…Serendipitously, zonisamide also demonstrated to improve motor symptoms in patients with Parkinson's disease when co-administered with levodopa (2,3), being currently approved in Japan as adjunctive therapy of Parkinson's disease at lower doses than those used in epilepsy (4). In addition, zonisamide revealed to be effective in relieving chronic and episodic cluster headaches (5). Underlying this widespread clinical use are probably the multiple mechanisms of action of zonisamide, encompassing the blockage of voltage-dependent sodium channels and T-type calcium channels, which contribute to neural membranes stabilization (6), inhibition of carbonic anhydrase (7), alteration of dopamine metabolism (2) and reduction of glutamate release (8).…”