Tiagabine: Efficacy and safety in adjunctive treatment of partial seizures

Purpose: To assess the efficacy and safety of tiagabine (TGB), a new antiep ileptic drug (AED), as add-on therapy in patients with refractory partial s eizures. Methods: This response-dependent study used an open-label screening phase ( in which patients were titrated to their optimal TGB dose. less than or equ al to 64 mg/day) followed by a double-blind, placebo-controlled, crossover phase. Initial eligibility criteria included (a) seizures inadequately cont rolled by existing AEDs, and (b) six or more partial seizures during an 8-w eek baseline period. Patients showing benefit from TGB (greater than or equ al to 25% reduction in total seizure rate relative to baseline) were eligib le for randomization into the double-blind phase, which comprised two 7-wee k assessment periods separated by a 3-week crossover period. Results: Forty-four (50%) of the 88 enrolled patients entered the double-bl ind phase of the study during which there were significant reductions compa red with placebo in all partial (p < 0.01), complex partial (p < 0.001), an d secondarily generalized tonic-clonic seizure rates (p < 0.05). Thirty-thr ee percent of patients experienced a reduction of <greater than or equal to >50% in the all partial seizure rate. Eight (22%) patients receiving TGB du ring the double-blind phase reported adverse events, of which dizziness and incoordination were the most frequent. Three patients withdrew from treatm ent during the double-blind phase because of adverse events; two during tre atment with TGB and one during treatment with placebo. TGB did not affect p lasma concentrations of other coadministered AEDs. Conclusions: TGB was significantly better than placebo in terms of seizure rate reduction and was generally well-tolerated in patients with difficult to control seizures.