INTRODUCTION: Increases in body weight gain are important, and clinically significant adverse effects of several antiepileptic drugs (AED) including valproate and gabapentin. Weight gain may contribute to medication non-compliance, discontinuation, and importantly, may have secondary medical implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment of partial seizures. The objective of the present evaluation was to examine the effects of LEV treatment on body weight in adult patients. METHODS: We analyzed data derived from four prospective, placebo-controlled randomized, clinical trials conducted in both in the US and Europe. Patients included in the present analysis were both men and women, greater than 16 years old, and who had LEV exposure for at least 1 month. Body weight was measured at baseline and at the final LEV study visit. Data are analyzed for all patients, by gender, body mass index (BMI), duration of LEV exposure and by concomitant AED treatment. Wilcoxan Signed Rank, or Rank Sum test used where appropriate, with significance assigned at P<0.05. Data are presented as mean values+/-1 S.D. RESULTS:Nine-hundred and seventy patients (age=37.5 years, 54% men/46% women) were evaluated. There were no significant differences in baseline demographics between LEV (n=631) or placebo (n=339) treated patient groups. Mean LEV dose and duration of treatment were 2053 mg/day (maximum dose of 4000 mg/day) and 125 days (maximum=181 days), respectively. Concomitant AED therapy included CBZ, PHT, VPA, PB, GBP, LTG, and VGB. For LEV-treated patients, no significant changes in body weight were noted. Mean body weight at baseline versus final study visit for LEV was 74.3+/-16.6 kg and 74.3+/-16.6 kg, respectively. For placebo-treated patients, baseline versus end of treatment weight was 72.4+/-15.4 kg and 72.7+/-15.9 kg, respectively, representing a slight, yet clinically trivial increase. Clinically significant weight change as defined as >7% change from baseline weight, occurred in 9% of LEV-treated patients (4.5% had increase in weight/4.5% decrease) versus 9.4% (5.9% had increase/3.5% decrease) in placebo-treated patients. Weight changes were not significantly different between groups. Neither baseline BMI, gender, or background AEDs, appeared to predispose to significant weight change for LEV-treated patients. CONCLUSIONS: We conclude that treatment with LEV at clinically relevant dosages is not associated with significant weight change. LEV would, therefore, appear to be a weight neutral AED.
RCT Entities:
INTRODUCTION: Increases in body weight gain are important, and clinically significant adverse effects of several antiepileptic drugs (AED) including valproate and gabapentin. Weight gain may contribute to medication non-compliance, discontinuation, and importantly, may have secondary medical implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment of partial seizures. The objective of the present evaluation was to examine the effects of LEV treatment on body weight in adult patients. METHODS: We analyzed data derived from four prospective, placebo-controlled randomized, clinical trials conducted in both in the US and Europe. Patients included in the present analysis were both men and women, greater than 16 years old, and who had LEV exposure for at least 1 month. Body weight was measured at baseline and at the final LEV study visit. Data are analyzed for all patients, by gender, body mass index (BMI), duration of LEV exposure and by concomitant AED treatment. Wilcoxan Signed Rank, or Rank Sum test used where appropriate, with significance assigned at P<0.05. Data are presented as mean values+/-1 S.D. RESULTS: Nine-hundred and seventy patients (age=37.5 years, 54% men/46% women) were evaluated. There were no significant differences in baseline demographics between LEV (n=631) or placebo (n=339) treated patient groups. Mean LEV dose and duration of treatment were 2053 mg/day (maximum dose of 4000 mg/day) and 125 days (maximum=181 days), respectively. Concomitant AED therapy included CBZ, PHT, VPA, PB, GBP, LTG, and VGB. For LEV-treated patients, no significant changes in body weight were noted. Mean body weight at baseline versus final study visit for LEV was 74.3+/-16.6 kg and 74.3+/-16.6 kg, respectively. For placebo-treated patients, baseline versus end of treatment weight was 72.4+/-15.4 kg and 72.7+/-15.9 kg, respectively, representing a slight, yet clinically trivial increase. Clinically significant weight change as defined as >7% change from baseline weight, occurred in 9% of LEV-treated patients (4.5% had increase in weight/4.5% decrease) versus 9.4% (5.9% had increase/3.5% decrease) in placebo-treated patients. Weight changes were not significantly different between groups. Neither baseline BMI, gender, or background AEDs, appeared to predispose to significant weight change for LEV-treated patients. CONCLUSIONS: We conclude that treatment with LEV at clinically relevant dosages is not associated with significant weight change. LEV would, therefore, appear to be a weight neutral AED.