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


CONCLUSIONS
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.
Ramsay
R Eugene
RE
Department of Neurology, University of Miami School of Medicine, Miami Veterans Affairs Medical Center, Miami, Florida, USA.
Perucca
Emilio
E
Robbins
Jefferey
J
Barrett
Jeannette A
JA
Spiegel
Katharyn
K
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin; D012189:Retrospective Studies; D055502:Secondary Prevention; D013997:Time Factors; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000927:Anticonvulsants; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid