Abstracts

RATIONALE: Many antiepileptic drugs (AEDs) can cause clinically significant weight changes, particularly weight gain. Even though weight change is a common occurrence and has potential health implications, AED-related weight changes are not well characterized. Clinically significant weight loss has been observed in patients with epilepsy being treated with topiramate (TPM) adjunctive therapy and monotherapy. Data from epilepsy clinical trials were analyzed to characterize TPM-associated weight loss.
METHODS: Clinical trial data (double-blind and open-label studies) from adult patients were analyzed. 1319 patients with refractory epilepsy (most receiving TPM adjunctive therapy) had body weight measurements at baseline and during TPM treatment. Body weight changes and absolute body weight were calculated at various periods for the population overall and for patient sub-groups stratified by dose, baseline body weight, and BMI. Relationships between weight change and pertinent clinical laboratory analytes were also assessed.
RESULTS: 65% of the 1319 patients included in the analyses were male; mean age was 36 yrs (range, 19-74 yrs). Most patients received TPM in addition to carbamazepine and/or phenytoin; [lt]20% of patients received valproate co-therapy. Weight was reduced in 85% of patients receiving TPM; mean body weight change was -3.8 kg (4.6% of baseline weight). Relative to baseline weights, the mean change was -9.6 kg (8.4%) for patients [gt]100kg and -3.2 kg (4.2%) for patients [lte]100 kg. In the sub-group of patients for whom body mass index (BMI) could be calculated, patients with BMI [gte]27 showed a mean weight loss of 7.4 kg (7.8%); with BMI [lt]27, mean weight loss was 3.1 kg (4.4%). Weight loss was observed within the first 3 mos of treatment. During long-term treatment ([gte]2 yrs), 45% of patients lost [gte]5% of their baseline weight; 20% lost [gte]10%. In patients treated for [gte]2 yrs, weight continued to decrease through 18 mos, and weight loss was maintained to at least 24 mos. Weight loss varied according to dose. Patients receiving [lt]200 mg/day TPM lost 2.2% of baseline weight compared with 3.7% in those receiving 200-399 mg/day TPM and 4.4% with 400-599 mg/day TPM. Changes in plasma glucose, total cholesterol, and blood pressure correlated with weight changes.
CONCLUSIONS: Up to 85% of adults lost weight without dietary changes while receiving TPM adjunctive or monotherapy for epilepsy. TPM- associated weight loss depends upon dose, duration of treatment, and baseline weight/BMI. Weight loss is gradual, continues for up to 18 mos, then plateaus. Analyses of clinically relevant data suggest that weight loss may be accompanied by changes in lipid profile, glycemic control, and blood pressure.
[Supported by: Johnson & Johnson Pharmaceutical Research & Development]; (Disclosure: Grant - Cyberonics, Elan, Novartis, Ortho-McNeil Pharmaceutical/Johnson & Johnson, Pfizer/Parke-Davis, UCB, Equity - GlaxoSmithKline, Ortho-McNeil Pharmaceutical/Johnson & Johnson, Pfizer/Parke-Davis, Consulting - GlaxoSmithKline, Novartis, Ortho-McNeil Pharmaceutical/Johnson & Johnson, Pfizer/Parke-Davis, UCB, Honoraria - Novartis, Ortho-McNeil Pharmaceutical/Johnson & Johnson, Pfizer/Parke-Davis, UCB)