Abstracts

Zonisamide has proven efficacy and tolerability in treating partial and generalized seizures in the general population. This study will determine response to zonisamide in patients with mental retardation/developmental disabilities and epilepsy. It will assess not only efficacy in reducing seizures but also evaluate the cognitive and behavioral effects of zonisamide in this special population. This ongoing prospective observational study recruited adult patients at the outpatient centers of the Long Island Jewish Comprehensive Epilepsy Center who were identified as appropriate candidates for treatment with zonisamide by their epileptologists. Patient[apos]s caregivers completed seizure calendars, the Aberrant Behavior Checklist (ABC), Behavioral Problem Inventory (BPI), and Habilitative Improvement Scale (HIS) at baseline, 3 months, 6 months, and 9 months. Zonisamide was titrated to 300mg total daily over 4 weeks, and it was adjusted further dependent on patient response up to a maximum of 600mg total daily. Of 25 patients enrolled, 10 have completed the study. There are 7 females, 3 males. Mean age is 39 years (25-60). Eight patients have a generalized epilepsy syndrome, and two have a partial epilepsy syndrome. The mean number of concomitant anti-epileptic medications is 2.5 (1-4). Mean total dose of zonisamide reached was 430mg daily (100-600). Decrease in seizures was seen in 6/10 patients, 3 of whom had [gt]50% decrease and 3 had [lt]50% decrease. Two patients had no change in seizure frequency, and two patients had an increase in seizures. Given the sample size, p value of p[lt]0.01 was used to determine significance. On the ABC, significant improvement was found in the domains assessing irritability, lethargy, hyperactivity, and inappropriate speech. The BPI found significant improvement in subsets evaluating the frequency and degree of aggressive behavior. On the HIS, there was overall improvement with a value p=0.000. Side effects included drowsiness in 2 patients, slurred speech in 1 patient, and unsteady gait in 1 patient. One patient developed rash and pancytopenia after taking zonisamide for 8 months. In the majority of patients, a reduction in seizure frequency was seen. Zonisamide was tolerated by most patients with significant improvement in behavioral domains. These findings indicate that zonisamide is an effective drug in the treatment of seizures while promoting positive behavioral effects in patients with developmental disabilities and epilepsy. (Supported by Eisai.)