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 (GAB A) uptake, at 3 dose levels vs placebo as adjunctive therapy in patien ts 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 hepat ic enzyme-inducing AEDs; dival-proex sodium or valproic acid was allow ed in combination with any of these drugs. Interventions: Placebo or t iagabine 4 times a day at 16, 32, or 56 mg daily. Main Outcome Measure s: Median change in 4-week CPS frequency and adverse events. Results: Median decreases in if-week CPS frequency for the 32-mg (-2.2) and 56- mg (-2.8) tiagabine groups were significantly greater than for the pla cebo (-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 < .00 1, respectively). Adverse effects were similar for placebo and tiagabi ne except for a significantly greater incidence of dizziness in the 32 -mg tiagabine group, tremor in the 32- and 56-mg groups, abnormal thin king (usually mental lethargy or difficulty concentrating) in the SG-m g 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.