Abstracts

RATIONALE:Topiramate (TPM) is an effective antiepileptic drug (AED). One notable side effect is weight loss seen in clinical trials in >50% of patients. The reasons for this have not been understood. We therefore investigated 51 epilepsy patients treated with TPM for up to one year to elucidate the extent and reasons for this weight loss. METHODS: 51 epilepsy patients on 1-2 concomitant AEDs were given TPM initially at 25mg/d and titrated up to 200 mg/d over a 3-month period. BMI, body composition, lean body mass, food consumption, glucose tolerance,and insuline release were among the most important variables that were followed. The concomitant AEDs were not changed and patients were instructed not to diet or consciously change their diet. RESULTS: At the time of this report 29 patients have completed the full one year evaluation period. Six patients stopped because of adverse events. 46 have continued in the study. The median dose of TPM in the 29 patients at 3-months was 150 mg/d but at one year it was 75mg/d. Reduction of dose was due to side effects which often abated with dose reduction. Seizure frequency for the one year period improved by >50% in 51% of patients.Six patients were seizure free during the first 3 months but only one was seizure free for the entire year. Mean weight reduction at one year was 5 kg. 55% lost >5% of body weight (8 patients with >10%). Food consumption was generally lower at 3 months but not at one year except for patients who lost >10%. They had a mean reduction of 150 kcal/day, a reduction of 6g fat/day and 25g carbohydrates/day. Fasting glucose and insuline release did not change from baseline. Only patients with BMI >30 had a significant reuction of body fat at one year but not lean body mass. CONCLUSIONS: TPM at low doses can cause >5% weight loss in >50% of patients. So far it appears that the mechanism is through reduction in food intake primarily causing reduction in mean body fat but not lean body mass.