Objective: To evaluate the efficacy and safety of 2 regimens of tiagabine as add-on therapy for patients with complex partial seizures (CPSs) that are refractory to other treatment.
Design: Randomized, double-blind, placebo-controlled, add-on, parallel-group trial with an 8-week baseline period, 12-week experimental period (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week termination period.
Setting: Twenty-six centers throughout the United States.
Patients: Three hundred fifty-one patients were enrolled, 318 were entered in the double-blind period, and 271 completed the study.
Interventions: Tiagabine, 16 mg 2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the fixed dose.
Main outcome measure: The median change in the 4-week rate of CPSs from baseline to experimental period.
Results: The median change from baseline was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2 times per day, and it was -1.2 CPSs in the group of patients who were given tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the patients who were given tiagabine 2 times per day and in 27% of the patients who were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P < or = .001 for each tiagabine-treated group compared with the placebo group). The most frequent adverse events involved the central nervous system and occurred in comparable proportions in the 3 treatment groups. Similar proportions of patients discontinued the study prematurely for adverse events.
Conclusions: Tiagabine administered 2 and 4 times daily as add-on pharmacotherapy was effective in reducing CPSs in patients with epilepsy whose conditions were refractory to treatment with other antiepileptic agents, and it was well tolerated.