Gabapentin (Neurontin) as Add‐on Therapy in Patients with Partial Seizures: A Double‐Blind, Placebo‐Controlled Study

Abstract

A multicenter, double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of gabapentin (Neurontin, GBP) as add-on therapy in 272 patients with refractory partial seizures who were receiving one to two standard antiepileptic drugs (AEDs). Efficacy assessments compared the frequency of partial seizures during the 12-week treatment phase (T) and the 12-week baseline period (B). The primary analysis compared data for patients receiving GBP 900 mg/day with placebo; the GBP 1,200-mg/day group provided dose-response data. Efficacy criteria were percentage of change in seizure frequency (PCH), responder rate (percentage of patients with > or = 50% reduction in seizure frequency), and response ratio, where RRatio = (T-B)/(T + B). Median PCH was -21.8% in the 900-mg/day group and -17.8% in the 1,200-mg/day group as compared with -0.3% in the placebo group. Responder rate was 22.9% in the 900-mg/day group and 10.1% in the placebo group (p = 0.020, Fisher's exact test). Adjusted mean RRatio was -0.136 in the 900-mg/day group and -0.025 in the placebo group (p = 0.0046, analysis of variance ANOVA). Results showed slightly greater improvement for the 1,200-mg/day than for the 900-mg/day group (RRatio = -0.157, responder rate 28.0%). Adverse events (AE) occurred in 69% of patients in the 900-mg/day group and in 64% in the 1,200-mg/day group as compared with 52% in patients receiving placebo as add-on therapy. The most frequent AE among patients treated with GBP were somnolence, dizziness, and fatigue. Clinical laboratory evaluations showed no clinically important trends and no evidence of hepatic or hematopoietic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of partial seizures with gabapentin: Double‐blind, placebo‐controlled, parallel‐group study*

“…Consistent with the safety profile of gabapentin shown in the previous study, [4][5][6] the most common adverse events were somnolence (44-51%) and dizziness (19-20%). Of note, placebo patients receiving other AED, also reported somnolence (20.7%) and dizziness (4.9%).…”

“…Each has demonstrated a statistically significant decrease in seizure frequency for gabapentin patients compared to placebo patients. [4][5][6] In addition, there was a 25% overall gabapentin responder rate, defined as the percentage of patients with ≥50% decrease in seizure frequency. 7 A phase II Japanese trial for gabapentin demonstrated a responder rate of approximately 22-24% when used as an adjunctive therapy in patients with refractory epilepsy receiving no more than three existing AED.…”

AUStralian Study of Titration to Effect Profile of Safety (AUS‐STEPS): High‐Dose Gabapentin (Neurontin) in Partial Seizures

“…The ethics committee at each center approved the protocol, and a written statement of informed consent was obtained before study entry. The study consisted of a screening visit, then an 8-week baseline, followed by a 24-week treatment period, with evaluations at the start and end of the baseline phase, and after 2,4,8,12,16,20, and 24 weeks of treatment. Patients were aged 12 years or older at study entry and were experiencing more than two partial-onset seizures per month with or without secondary generalization despite therapy with one to three concurrent antiepileptic drugs (AEDs).…”

“…Quality of life was assessed by administering the QOLIE-10 questionnaire at screening, at week 16 of treatment, and at the final visit. Patients were assessed at screening and at weeks 0, 2,4,8,12,16,20, and 24 of the treatment phase. Responders were defined as those patients who recorded a ജ50% reduction in seizure frequency compared with the baseline phase.…”

“…Controlled phase II and III clinical trials have indicated that GBP is associated with a dose-related increase in efficacy at dosages of 600 to 1,800 mg/day (1,2). Initial studies with higher dosages have indicated good tolerability with long-term use of ഛ2,400 mg/day (3), and short-term use of ഛ4,800 mg/day (4,5).…”