A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF TIAGABINE GIVEN 3-TIMES DAILY AS ADD-ON THERAPY FOR REFRACTORY PARTIAL SEIZURES

In a multicentre, double-blind, parallel-group, placebo-controlled tri al, a three-times daily regimen of tiagabine was evaluated as add-on t herapy in 154 adult patients with refractory partial seizures. A total of 77 patients were randomised to treatment in each arm. Tiagabine HC l was titrated from an initial dose of 12-30 mg/day over 4 weeks. Duri ng the 12-week fixed-dose period, there was a significant reduction in the median 4-weekly seizure rate for all partial seizures and simple partial seizures (P < 0.05 in each case). Furthermore, the proportion of patients with a reduction of 50% or more in all partial seizures wa s higher in the tiagabine group than in the placebo group (14 versus 6 %), though the difference did not achieve statistical significance. Th e difference with respect to simple partial seizures was significant ( 21 versus 6%, P < 0.01). The percentage of patients achieving an incre ase of at least 50% in the proportion of days free of all partial seiz ures was significantly greater in the tiagabine group compared to plac ebo (14 versus 4%, P < 0.01). Tiagabine did not appear to influence th e plasma concentrations of other concomitant antiepileptic drugs and w as generally well tolerated, with most drug-related adverse events bei ng mild or moderate in severity. The most common adverse events were d izziness, asthenia, headache and somnolence. Adverse event incidence w as similar between tiagabine and placebo groups, except for dizziness which was more common with tiagabine (29 versus 10%, P < 0.01). Tiagab ine had no significant effects on laboratory tests or vital signs. The present study shows that tiagabine, at a dose of 10 mg administered t hree-times daily, which is at the lower end of the usual recommended d ose range (30-50 mg/day, tiagabine base), is generally well tolerated and demonstrates efficacy for the treatment of refractory partial seiz ures. (C) 1998 Elsevier Science B.V. All rights reserved.