Objective: To determine the efficacy and tolerability o tiagabine, a new antiepileptic drug (AED) that inhibits γ-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 p base. 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-rag 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.