Abstracts

RATIONALE: Weight loss appears to be common in patients treated with topiramate (TPM) as add-on therapy or as monotherapy. Data from clinical trials in adolescents and adults suggested a relationship between degree of weight loss and baseline body weight. We conducted a prospective study to evaluate weight changes and associated metabolic changes in patients with epilepsy treated with TPM for 1 yr to identify predictors of weight loss.
METHODS: In 49 adults with partial-onset seizures with or without secondary generalization, TPM was added to 1-2 baseline AEDs at a starting dose of 25 mg/day and a target dose of 200 mg/day at 3 mos. Patients were instructed not to change their diet. Data collected at baseline, 3 mos and 1 yr included seizure counts, body weight, body composition, food intake, glucose, insulin, serum lipids, and leptin levels.
RESULTS: For the intent-to-treat population (N=49), the mean TPM dose was 81 mg/day (range, 21-154) at 3 mos and 129 mg/day (range, 45-262) at 1 yr. The median percentage seizure reduction was 59% at 3 mos and 67% at 1 yr; 35% and 18% of patients had been seizure-free since baseline at the 3-mo and 1-yr visits, respectively. Mean baseline weight was 78 kg (range, 46-124 kg). Mean weight reductions (kg and % baseline weight) overall were: 3 mos, 2.7 kg and 3.6%; 1 yr, 4.8 kg and 6.0%. However, weight reductions were greater in obese patients (BMI [gt]30): 3 mos, 3.4 kg and 3.5%; 1 yr, 7.6 kg and 7.7%. Among patients with BMI [gt]30, weight was reduced [gt]5% from baseline in 23% of patients at 3 mos and 54% at 1 yr; baseline weight was reduced [gt]10% in 8% and 31%, respectively. At 3 mos, the only statistically significant factors predicting weight loss were lower baseline caloric intake and reduced caloric intake (p[lt]0.001). At 1 yr, the most significant predictor of weight reduction (kg) was higher baseline BMI (p[lt]0.0005), predicting 30% of the weight reduction. However, a statistically significant correlation between percent weight reduction at 1 yr and higher baseline leptin levels was also observed. Improvements in metabolic parameters in patients receiving TPM included improvements in glucose, insulin, and HDL levels at 1 yr, particularly in patients with a baseline BMI [gt]30.
CONCLUSIONS: At doses [lt]200 mg/day, TPM improved seizure control. Weight was reduced in most patients; absolute and percent weight reduction was greater at 1 yr than at 3 mos, suggesting a sustained effect on weight. Early in therapy, weight reduction correlated most strongly with decreased food consumption and lower baseline caloric intake. With continued therapy, baseline BMI and higher baseline leptin levels were the strongest predictors of weight loss at 1 yr. Decreases in weight were associated with improvements in metabolic parameters, particularly in obese patients.
Support: R.W.Johnson Pharmaceutical Research Institute
Disclosure: Salary - Hellstrom, Stagge- Janssen-Cilag; Grant - Ben-Menachem- R.W.Johnson Pharmaceutical Research Institute; Consulting - Ben-Menachem- R.W.Johnson Pharmaceutical Research Institute; Stock - Hellstrom, Stagge- Janssen-Cilag