Psychosis Following Initiation of Zonisamide

To the Editor: Zonisamide is a novel anticonvulsant used as adjunctive treatment in combination with other antiepileptic medications for partial seizures. We present a case report of a patient who developed psychotic symptoms after initiation of zonisamide and stabilized only after zonisamide cessation, psychiatric hospitalization, and antipsychotic medication treatment.

Zonisamide has been used in Japan and Korea for over 15 years. Several Japanese-language case studies report psychosis and/or mania with zonisamide (1 – 3) . Psychosis incidence in one study ranged from 1.9% to 2.3% of patients treated with zonisamide (2) . In another study of 74 patients, incidence of psychosis ranged from 13% to 18% (1) . One-half of these episodes occurred within one year following zonisamide initiation, and 11 out of 14 occurred within three years. Patients who experienced psychosis were younger than those who did not. A 12-year-old child whose psychosis subsided with cessation was retried with zonisamide until her psychosis became irreversible.

Previous reports noting poor correlation between starting zonisamide and psychosis onset could not definitively conclude that zonisamide was the causative agent (1, 4) . We cannot rule out that our patient’s symptoms resulted from interictal psychosis. However, her 41-year seizure history, previously unaccompanied by psychosis, leads us to believe that this psychotic episode is related to zonisamide treatment.

Zonisamide is used increasingly in the United States for seizure control and, off-label, for weight loss. We agree with Japanese recommendations that zonisamide be halted in epileptic patients with new-onset psychosis and not be retried.