Tiagabine in clinical practice

Among the newly introduced antiepileptic drugs (AEDs), tiagabine (TGB) stan ds out as a compound with a well-understood and documented mechanism of act ion. It is a lipophilic derivative of nipecotic acid that blocks gamma -ami nobutyric acid (GABA) reuptake by inhibition of the GAT-I transportation sy stem, and that has no other significant pharmacodynamic effect. The relatio nship between intake and blood levels is linear. Usual daily maintenance do ses range from 20 to 50 mg. It is completely absorbed by the gastrointestin al tract, and its half-life is similar to7-9 h. TGB is sensitive to enzyme induction: when coprescribed with enzyme-inducing AEDs, its half-life is sh ortened to 2-3 h, whereas the daily dosage has to be increased into the upp er range. It should be given 3 times per day. Placebo-controlled, double-bl ind, add-on studies conducted in patients with drug-resistant focal epileps ies have demonstrated its efficacy and overall safety. The clinical benefit s appear to persist over time. Data on its use in monotherapy are scanty. T he efficacy and tolerability of TGB in the pediatric age still remain to be investigated adequately. In daily practice, TGB appears to be a safe drug, but mild to moderate side effects are frequently seen, especially during t itration: these include dizziness and fatigue, and are clearly abated when the drug is absorbed during meals. Titration should be especially slow, no faster than 5 mg weekly. Clinicians also should beware of the possible occu rrence of confusion, which may be misdiagnosed as absence status, a short-l asting, quickly reversible central nervous system-related side effect that appears to be correlated with the peak plasma concentrations of TGB. Partic ularly beneficial indications for TGB and/or AED associations including TGB have not been pointed out, but there is a hint that it works best in tempo ral lobe epilepsies.