A multicentre, open label, randomised, parallel group study compared the efficacy, tolerability and safety of two dosing regimens, t.i.d. and b.i.d., of tiagabine as an adjunctive therapy for the treatment of refractory patients with partial seizures. A total of 347 patients were randomised and treated (175 t.i.d. and 172 b.i.d.). Each group was administered the same daily dose of tiagabine incremented stepwise during a 12-week fixed-schedule titration period to a target dose of 40 mg/day. The patients were followed for a further 12-week flexible continuation phase. A significantly greater number of patients in the t.i.d. group completed the fixed schedule titration period (81.4% versus 73.1%; 95% CI of odds ratio = 0.331, 0.970; p = 0.038). The proportion of responders (patients showing at least a 50% decrease in all-seizure frequency from baseline) was similar for both groups (42.3% for b.i.d. and 47.1% for t.i.d.) during the last 8 weeks of the flexible phase and seven (4.0%) patients in the b.i.d. group were seizure-free compared to 14 (8.1%) patients in the t.i.d. group. Adverse events were of similar incidence in both groups, and mainly occurred during the fixed schedule titration period; they were mainly mild and CNS-related with somnolence being the most frequently reported.
Conclusion: Tiagabine was effective as add-on treatment of refractory partial seizures. Although both regimens appear to offer a similar efficacy and safety profile, significantly more patients completed the study in the t.i.d. group compared to b.i.d., probably as a consequence of a lesser tolerability when high doses are given undivided. These results confirm that a slow titration and appropriate adjustment of dosing are essential conditions to ensure optimal use of tiagabine.