In a multicentre, double-blind, parallel-group, placebo-controlled trial, a three-times daily regimen of
tiagabine was evaluated as add-on
therapy in 154 adult patients with refractory
partial seizures. A total of 77 patients were randomised to treatment in each arm.
Tiagabine HCl was titrated from an initial dose of 12-30 mg/day over 4 weeks. During 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 was higher in the
tiagabine group than in the placebo group (14 versus 6%), though the difference did not achieve statistical significance. The difference with respect to
simple partial seizures was significant (21 versus 6%, P < 0.01). The percentage of patients achieving an increase of at least 50% in the proportion of days free of all
partial seizures was significantly greater in the
tiagabine group compared to placebo (14 versus 4%, P<0.01).
Tiagabine did not appear to influence the plasma concentrations of other concomitant
antiepileptic drugs and was generally well tolerated, with most
drug-related adverse events being mild or moderate in severity. The most common adverse events were
dizziness,
asthenia,
headache and
somnolence. Adverse event incidence was similar between
tiagabine and placebo groups, except for
dizziness which was more common with
tiagabine (29 versus 10%, P < 0.01).
Tiagabine had no significant effects on laboratory tests or vital signs. The present study shows that
tiagabine, at a dose of 10 mg administered three-times daily, which is at the lower end of the usual recommended dose range (30-50 mg/day,
tiagabine base), is generally well tolerated and demonstrates efficacy for the treatment of refractory
partial seizures.