Rapid onset of seizure suppression with pregabalin adjunctive treatment in patients with partial seizures.

PURPOSE: To determine the time at which pregabalin demonstrates seizure-suppressing activity when given as adjunctive treatment to patients with refractory partial seizures. METHODS: Data from four similar 12-week, randomized, double-blind, placebo-controlled, parallel-group trials in patients with refractory partial seizures were pooled to provide an adequate sample to compare the proportion of patients free of seizures on each study day between pregabalin (combined 150-600 mg/day groups) and placebo (combined groups). A generalized estimating equation (GEE) statistical model was used to perform pairwise comparisons on each study day. In several pregabalin dosage groups the dosage was escalated during days 1-7, whereas in others pregabalin was initiated at a fixed dosage without escalation. RESULTS: The proportion of patients free of seizures on any treatment day was greater in the combined pregabalin groups compared with baseline. Differences were not observed between the placebo group and baseline. A significantly greater proportion of patients were free of seizures in the combined pregabalin 150-600 mg/day and the pregabalin 600 mg/day fixed-dosage groups compared with the placebo groups from treatment day 2 onward (p < 0.05). From day 8 (coinciding with completion of the 1-week dosage-escalation period in two studies) onward, the proportion of patients free of seizures per day in the pregabalin groups remained relatively constant. DISCUSSION: This exploratory analysis of a refractory population using a rigorous endpoint demonstrates that pregabalin rapidly reduced the frequency of partial seizures. At the dosing schemes most commonly used in placebo-controlled trials, significant seizure-suppressing activity was observed after only 2 days of treatment.

Reduction of secondarily generalized tonic-clonic (SGTC) seizures with pregabalin.

PURPOSE: To determine whether pregabalin reduces SGTC seizures in clinically refractory epilepsy. DESIGN: Post hoc analysis performed on pooled data from three double-blind, placebo-controlled trials of similar design. PARTICIPANTS: Patients with partial seizures who failed > or =2 antiepileptic drugs at maximally tolerated doses. This analysis excluded those who did not have an SGTC seizure during baseline or treatment periods. OUTCOME MEASURE: Absolute and conditional reduction analyses examined change from baseline in SGTC seizure rates. The absolute reduction analysis used response ratio (RRatio) to compare reduction in seizure-frequency from baseline (B) during a 12-week treatment (T) period [RRatio=((T-B)/(T+B))x100]. The conditional analysis examined proportional risk of having SGTC seizure if a partial seizure had occurred. RESULTS: Of 1052 intent-to-treat patients, 409 were included. Sixteen were seizure-free during treatment and not included in the conditional analysis. A significant reduction in absolute SGTC seizures from baseline was observed in patients receiving pregabalin 600 mg/day (treatment RRatio, -33 versus placebo, -3.7; P=0.0005). A lower dose of pregabalin (300mg/day), administered in one study, demonstrated a trend (nonsignificant) toward reduced SGTC seizures (treatment, -24.7 versus placebo, -10.0; P=0.2493). CONCLUSION: As adjunctive therapy, pregabalin 600 mg/day is effective in reducing the absolute frequency of SGTC seizures in patients with refractory partial epilepsy, but not secondary generalization.