Efficacy and Safety of Levetiracetam (3,000 mg/Day) as an Adjunctive Therapy in Chinese Patients with Refractory Partial Seizures

Abstract

Aim: To evaluate the efficacy and safety of 3,000 mg daily levetiracetam (LEV; Keppra) as an adjunctive therapy for Chinese patients with refractory partial seizures. Methods: This randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 4-week titration interval and a 12-week maintenance period, and concluded with a 4-week medication withdrawal period or entered an open-label study. LEV was compared with placebo. Results: The 50% responder rate (the proportion of patients with a minimum of 50% reduction in partial seizure frequency) occurred in 46.4% of the LEV group, compared with 39.3% of the placebo group (p = 0.590). The median of the absolute weekly frequency reduction from baseline of partial seizures was 0.66 per week for LEV versus 0.48 per week for placebo (p = 0.187). The most common treatment-emergent adverse events, mostly mild to moderate in severity, were somnolence, dizziness and agitation. Conclusion: In this study, adjunctive therapy with LEV 3,000 mg daily was well tolerated but not as effective as expected in controlling partial seizures in this study population. Considering the lower mean weight of this study population, we suggest the dosage of LEV 3,000 mg daily may contribute to the results.

Efficacy and Tolerability of Second and Third Generation Anti-epileptic Drugs in Refractory Epilepsy: A Network Meta-Analysis

“…42 28.2; 31.3Levetiracetam(13); Placebo(11)750 mg/dYesBen-Menachem, E. 15 37.0; 36.0Levetiracetam(181); Placebo(105)3000 mg/dYesYesShorvon, S. D. 34 37.0Levetiracetam(212); Placebo(112)1000, 2000 mg/dYesYesYesXiao, Z. 39 32.8; 32.5Levetiracetam(28); Placebo(28)3000 mg/dYesYesYesTsai, J. J. 37 32.8; 31.7Levetiracetam(47); Placebo(47)1000–2000 mg/dYesYesYesBetts, T. 16 37.5; 35Levetiracetam(80); Placebo(39)6000 mg/dYesYesYesFrench, J.…”

From clinical trials of antiepileptic drugs to treatment

“…If 2 active treatments are not found to differ and placebo is not included as a comparator, the argument could be made that in the specific setting in which the trial was conducted , both treatments might have been equally ineffective . The latter possibility is far from remote because, historically, adjunctive‐therapy RCTs have not always differentiated established active treatments from placebo, at least in certain settings . Recently, concerns with assay sensitivity in active control trial designs were rekindled by the results of a double‐blind flexible‐dose RCT in which no difference in seizure outcomes was found between pregabalin and gabapentin, contrary to the expectation from earlier trials that pregabalin would show superior efficacy …”

“…6,17 The latter possibility is far from remote because, historically, adjunctive-therapy RCTs have not always differentiated established active treatments from placebo, at least in certain settings. 9,10,18 Recently, concerns with assay sensitivity in active control trial designs were rekindled by the results of a double-blind flexible-dose RCT in which no difference in seizure outcomes was found between pregabalin and gabapentin, contrary to the expectation from earlier trials that pregabalin would show superior efficacy. 19 Despite these limitations, there is an increasing interest in including established active controls in adjunctive-therapy trials of new AEDs.…”

Epilepsy surgery, antiepileptic drug trials, and the role of evidence

“…Of 169 potential articles identified, 11 satisfied inclusion criteria and constitute the dataset for the analysis (Ben‐Menachem et al, 2007; Elger et al, 2007; Naritoku et al, 2007; Porter et al, 2007; Faught et al, 2008; Elger et al, 2009; Halasz et al, 2009; Lee et al, 2009; Peltola et al, 2009; Wu et al, 2009; Xiao et al, 2009). All seven studies that indicated a date of study onset started after 2002; the date of acceptance for publication was after 2006 for the remaining four therapy studies.…”