TIAGABINE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND THERAPEUTIC POTENTIAL IN THE MANAGEMENT OF EPILEPSY

Tiagabine is a gamma-aminobutyric acid (GABA) uptake inhibitor which i s structurally related to nipecotic acid but has an improved ability t o cross the blood-brain barrier. Clinical trials have shown that tiaga bine is effective as add-on therapy in the management of patients with refractory partial epilepsy. In short term studies of this indication , tiagabine less than or equal to 64 mg/day for 7 to 12 weeks reduced the complex partial and simple partial seizure frequency by greater th an or equal to 50% in 8 to 31 and 28.2 to 37% of patients,respectively . tiagabine appeared to produce an sustained reduction in seizure freq uency in studies of up to 12 months' duration. Data from preliminary s tudies are currently insufficient to confirm the usefulness of tiagabi ne when used as monotherapy or in the treatment of children with epile psy. Further studies are, therefore,necessary to more fully elucidate the efficacy of the drug in these settings. Adverse events associated with tiagabine are primarily CNS-related and include dizziness, asthen ia, nonspecific nervousness and tremor. Skin rash or psychosis occurre d with similar frequencies among tiagabine- and placebo-treated patien ts. With long term administration (greater than or equal to 1 year for many patients), the profile and incidence of adverse events was simil ar to that for short term therapy. Tiagabine does not appear to affect the hepatic metabolism of other drugs such as carbamazepine and pheny toin. Possible disadvantages of tiagabine include its short plasma eli mination half-life, necessitating 2 to 4 times daily administration,an d its inducible hepatic metabolism. Thus, tiagabine is a new antiepile ptic agent with a novel mechanism of action, which has demonstrated ef ficacy in the adjunctive treatment of patients with refractory partial epilepsy. further investigation of the efficacy of tiagabine is expec ted to provide a clearer definition of its place in the treatment of e pilepsy and its relative merits in relation to other antiepileptic dru gs.