Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.
BACKGROUND
Pregabalin is an alpha(2)-delta ligand that has anxiolytic, analgesic, and anticonvulsant properties.


OBJECTIVE
To establish the efficacy, safety, and tolerability of pregabalin administered twice-daily (BID) without dose titration as adjunctive treatment in patients with partial seizures and to confirm the dose-response relationship.


METHODS
This 76-center, double-blind, randomized, placebo-controlled, parallel-group study consisted of an 8-week baseline and a 12-week double-blind phase. Patients with refractory partial seizures on one to three antiepileptic drugs were randomly assigned to one of five treatment groups (placebo or 50, 150, 300, and 600 mg/d pregabalin, all administered BID). Efficacy was assessed using seizure frequency reduction and responder rate (> or =50% seizure reduction from baseline). Pharmacokinetic parameters were estimated.


RESULTS
A total of 453 patients were included in the intent-to-treat analysis. The median baseline seizure rate was 10 per month. Seizure frequency reductions from baseline were 7% (placebo; n = 100), 12% (50 mg/d; n = 88), 34% (150 mg/d; n = 86), 44% (300 mg/d; n = 90), and 54% (600 mg/d; n = 89). Responder rates (> or =50% seizure reduction) were 14% (placebo), 15% (50 mg/d), 31% (150 mg/d), 40% (300 mg/d), and 51% (600 mg/d). Discontinuation rates due to adverse events were 5% (placebo), 7% (50 mg/d), 1% (150 mg/d), 14% (300 mg/d), and 24% (600 mg/d). The 150-, 300-, and 600-mg/d pregabalin groups were associated with greater reductions in seizures (p < or = 0.0001) and greater responder rates compared with the placebo group (p < or = 0.006). There was a favorable dose-response trend for both seizure reductions (p < or = 0.0001) and responder rate (p < or = 0.001).


CONCLUSIONS
Adjunctive therapy with pregabalin 150, 300, and 600 mg/d, given in twice-daily doses without titration, is significantly effective and well tolerated in the treatment of patients with partial seizures as demonstrated in patients with refractory partial seizures.
French
J A
JA
University of Pennsylvania Medical Center Epilepsy Center, Philadelphia, USA. frenchj@mail.med.upenn.edu
Kugler
A R
AR
Robbins
J L
JL
Knapp
L E
LE
Garofalo
E A
EA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015220:Calcium Channels / Q000187:drug effects; D002648:Child; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin; D012449:Safety; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000927:Anticonvulsants; C480968:CACNA2D2 protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid