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).
Design: 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.
Setting: Twenty-one US medical centers.
Patients: 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.
Interventions: Placebo or tiagabine 4 times a day at 16, 32, or 56 mg daily.
Main outcome measures: 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.