Tiagabine for complex partial seizures: a randomized, add-on, dose-response trial.
OBJECTIVE
To determine the efficacy and tolerability of tiagabine, a new antiepileptic drug (AED) that inhibits gamma-aminobutyric acid (GABA) uptake, at 3 dose levels vs placebo as adjunctive therapy in patients with intractable complex partial seizures (CPS).


METHODS
Randomized, double-blind, placebo-controlled study with a parallel-group, add-on design, starting with a 12-week unblinded baseline phase followed by a 20-week double-blind treatment phase.


METHODS
Twenty-one US medical centers.


METHODS
Patients (N = 297) aged 12 to 77 years, previously diagnosed as having CPS and receiving stable regimens of 1 to 3 hepatic enzyme-inducing AEDs; divalproex sodium or valproic acid was allowed in combination with any of these drugs.


METHODS
Placebo or tiagabine 4 times a day at 16, 32, or 56 mg daily.


METHODS
Median change in 4-week CPS frequency and adverse events.


RESULTS
Median decreases in 4-week CPS frequency for the 32-mg (-2.2) and 56-mg (-2.8) tiagabine groups were significantly greater than for the placebo (-0.7) group (P = .03 and P < .03, respectively); 20% and 29% of patients in the 32- and 56-mg groups had a 50% or greater reduction in the frequency of CPS vs 4% in the placebo group (P = .002 and P < .001, respectively). Adverse effects were similar for placebo and tiagabine except for a significantly greater incidence of dizziness in the 32-mg tiagabine group, tremor in the 32- and 56-mg groups, abnormal thinking (usually mental lethargy or difficulty concentrating) in the 56-mg group, and depressed mood in the 16- and 56-mg groups.


CONCLUSIONS
Tiagabine is efficacious and well tolerated as adjunctive therapy for CPS; there is a clear dose-response relationship.
Uthman
B M
BM
Veterans Affairs Medical Center, and the Department of Neurology and Brain Institute, University of Florida College of Medicine, Gainesville 32608, USA.
Rowan
A J
AJ
Ahmann
P A
PA
Leppik
I E
IE
Schachter
S C
SC
Sommerville
K W
KW
Shu
V
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; 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*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009557:Nipecotic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D000078308:Tiagabine; D016896:Treatment Outcome
D000927:Anticonvulsants; D009557:Nipecotic Acids; D000078308:Tiagabine