Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy.

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy. METHODS: A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. Following a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin 600 mg/day administered twice daily (BID) or three times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing > or =50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population. RESULTS: Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID (p < or = 0.0001) and 44% for pregabalin BID (p < or = 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo (p < or = 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia. CONCLUSIONS: Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice daily or three times daily schedule with similar efficacy and tolerability results.

Cognitive abilities and adjustment with gabapentin: results of a multisite study.

The cognitive and quality of life effects of gabapentin are not yet well explored. While preliminary work in the area has provided positive findings, a large double-blinded study has been needed to explore this area more thoroughly. From 24 sites in North America, 201 adults were studied who had uncontrolled complex partial seizures with or without secondary generalization. Attempts were made to convert each patient from one or two marketed antiepileptic drugs (AEDs) taken in baseline to gabapentin monotherapy (600, 1200, or 2400 mg/day). Tests of cognitive abilities and adjustment were administered at the end of the 8-week baseline period and at the end of the 26-week double-blind treatment period. Analyses of baseline to treatment period changes were conducted for each dose group in comparison with a reference group of placebo-treated patients from another study. In the area of cognitive functioning, no changes in any of the gabapentin groups were found in comparison with the reference group. In the area of adjustment and mood, however, improvement with gabapentin administration was noted on several variables pertaining to emotional and interpersonal adjustment. These results are consistent with findings from previous studies.

A double-blind trial of gabapentin monotherapy for newly diagnosed partial seizures. International Gabapentin Monotherapy Study Group 945-77.

BACKGROUND: Gabapentin is widely approved as add-on therapy for epilepsy treatment for partial seizures with and without secondary generalization. To investigate the efficacy of gabapentin administered as monotherapy in patients with newly diagnosed partial epilepsy, a randomized double-blind trial was performed. METHODS: Eligible patients were randomized to receive one of three masked doses of gabapentin (300, 900, or 1,800 mg/day) or open-label carbamazepine (600 mg/day) and kept daily seizure diaries throughout the study. After titration, patients entered a 24-week evaluation phase. Patients were required to exit the study if they experienced an exit event, defined as a total of three simple or complex partial seizures, one generalized tonic-clonic (GTC) seizure, or status epilepticus. Patients could be withdrawn for lack of efficacy, adverse events, or noncompliance. Kaplan-Meier statistics were used to estimate the probability that patients would continue in the study without having an exit event. RESULTS: Time to exit event was longer for patients on 900 mg/day (n = 72) or 1,800 mg/day (n = 74) of gabapentin than for patients receiving 300 mg/day (n = 72; p = 0.0395 and 0.0175, respectively). The most clinically relevant measure of retention on treatment (exit event plus adverse event withdrawal rate) was similar for carbamazepine (n = 74) and 1,800 mg/day gabapentin (54% versus 57%) but was lower (better) for 900 mg/day gabapentin (44%). No unexpected new adverse events emerged with gabapentin monotherapy. CONCLUSIONS: Gabapentin at 900 or 1,800 mg/day is effective and safe as monotherapy for patients with newly diagnosed partial epilepsy.