Abstracts

RATIONALE: Zonisamide is a new anti-epileptic drug (AED) approved as add on therapy for partial seizures. Although zonisamide has been widely used in Japan over the past decade, it is fairly new in the US market. Premarketing data indicates a 25 % incidence of behavioral adverse events (AEs) in patients receiving zonisamide. In this study we report the incidence and characteristics of behavioral AEs in US in a multicenter post-marketing cohort.
METHODS: We analyzed data from the PADS (Post-marketing Antiepileptic Drug Survey) on behavioral AEs in 100 consecutive patients initiated on zonisamide at least 6 months prior to the study. PADS is a prospective registry provided by a consortium of 16 epilepsy centers to study the population treated with new AEDs. Patients at each center are prospectively and consecutively entered. Initiation forms include demographic data, as well as data on seizure type/frequency, past behavioral and psychiatric disturbances, and current/past antiepileptic drug use. Follow-up forms include seizure outcome, adverse events, reason for discontinuation, if applicable, dose and titration rate.
RESULTS: We obtained follow up on 67 patients, with a mean follow up of 203.5 [plusminus] 133.3 days. Males 24, females 43, with mean age 38.0 [plusminus] 16.3 vs 32.4 [plusminus] 9.3 years for patients with behavioral AEs (p[gt]0.29). Total number of patients reporting behavioral problems while on zonisamide was 8(11.9%). Behavioral AEs led to discontinuation of zonisamide in 6 (8.9%). The average zonisamide dose in patients with behavioral AEs was 250 [plusminus] 192.7mg/day, vs. 292.9 [plusminus] 178.5 mg/day in the total zonisamide population (p[gt]0.47). Behavioral AEs (pts could report [gt]1) included; irritability (3), aggression (1), depression (1), agitation (1), mood swings (3), suicide attempt (2) psychosis (1). A history of past psychiatric/behavioral problems/mental retardation was noted in 37% of patients with behavioral adverse events vs 30.5% of those without behavioral AEs.
CONCLUSIONS: Behavioral AEs in patients receiving zonisamide lead to discontinuation only in 8.9%. No demographic group appeared at increased risk. No dose differences were found between patients with behavioral AEs and total zonisamide population. Behavioral AEs seen with zonisamide appear in accord with other AEDs, and with premarketing data.
[Supported by: The PADS survey has received contributions from: Ortho-McNeil, Cyberonics, Abbott, Glaxo-Wellcome, Novartis, Elan, and UCB Pharma]; (Disclosure: Other - The PADS survey has received contributions from: Ortho-McNeil, Cyberonics, Abbott, Glaxo-Wellcome, Novartis, Elan, and UCB Pharma)