Mechanistic similarities underlying neuropathic pain and epilepsy suggest that anticonvulsants can be used for treating neuropathic pain. This open-label prospective study assesses the use of zonisamide in patients with chronic neuropathic pain. Fifty-five patients were initiated on zonisamide, given 100 mg every fourth night and titrated to a stable maintenance dosage (mean=285 mg/d, range=100 to 700 mg/d). Patients rated their pain on a 0 to 10 scale in pain diaries. After > or =3 months on a stable maintenance zonisamide dosage, pain ratings were compared with baseline. Adverse events (AEs) were monitored. Forty-two patients had efficacy data available. Fifteen patients (35.7%) had a >50% improvement in daily pain scores; 10 patients (23.8%) had a 25% to 50% improvement. Zonisamide was well tolerated; only 5 patients discontinued for AEs (drowsiness, nausea, and itching). These results suggest that zonisamide may be useful for treating neuropathic pain. Further investigation in double-blind, placebo-controlled trials is warranted.