A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures.
OBJECTIVE
This study assessed the comparative efficacy of pregabalin for refractory partial seizures.


METHODS
Four-hundred and thirty-four patients with partial seizures were randomized to pregabalin, lamotrigine, or placebo as adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks), pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages of 300mg/day for both. In phase II (6 weeks), patients not yet seizure-free were increased to pregabalin 600mg/day or lamotrigine 400mg/day.


RESULTS
During phase I, there was a nonsignificant trend toward a greater reduction in seizures with pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment, pregabalin showed a median percentage reduction from baseline in seizure frequency of -20.0% (p=.001) versus placebo, and -9.7% (p=.080) versus lamotrigine. The responder rate (> or =50% reduction in seizure frequency) for pregabalin exceeded that of placebo (36% vs 21%; p=.007) and lamotrigine (36% vs 24%; p=.04). Adverse events were consistent with the known safety profiles of pregabalin and lamotrigine.


CONCLUSIONS
Pregabalin was demonstrated to be noninferior to lamotrigine in the treatment of refractory partial seizures. Overall conclusions were complicated by an unusually large and heterogeneous placebo response.
Baulac
Michel
M
Hopital Pitié-Salpêtrière, APHP, Universite PARIS VI and INSERM UMR_S 975, Cortex & Epilepsy, Clinique Neurologique, Hopital de la Pitié-Salpêtrière, Paris, France. michel.baulac@psl.aphp.fr
Leon
Teresa
T
O'Brien
Terence J
TJ
Whalen
Edward
E
Barrett
Jeannette
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004244:Dizziness / Q000139:chemically induced / Q000209:etiology; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D000069583:Pregabalin; D012640:Seizures; D014227:Triazines / Q000008:administration & dosage* / Q000009:adverse effects; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D014227:Triazines; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077213:Lamotrigine