Tiagabine is a
gamma-aminobutyric acid (
GABA) uptake inhibitor which is structurally related to
nipecotic acid but has an improved ability to cross the blood-brain barrier. Clinical trials have shown that
tiagabine is effective as add-on
therapy in the management of patients with refractory
partial epilepsy. In short term studies of this indication,
tiagabine < or = 64 mg/day for 7 to 12 weeks reduced the complex partial and simple partial seizure frequency by > or = 50% in 8 to 31 and 28.2 to 37% of patients, respectively.
Tiagabine appeared to produce a sustained reduction in seizure frequency in studies of up to 12 months' duration. Data from preliminary studies are currently insufficient to confirm the usefulness of
tiagabine when used as monotherapy or in the treatment of children with
epilepsy. 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,
asthenia, nonspecific nervousness and
tremor.
Skin rash or
psychosis occurred with similar frequencies among
tiagabine- and placebo-treated patients. With long term administration (> or = 1 year for many patients), the profile and incidence of adverse events was similar to that for short term
therapy.
Tiagabine does not appear to affect the hepatic metabolism of other drugs such as
carbamazepine and
phenytoin. Possible disadvantages of
tiagabine include its short plasma elimination half-life, necessitating 2 to 4 times daily administration, and its inducible hepatic metabolism. Thus,
tiagabine is a new
antiepileptic agent with a novel mechanism of action, which has demonstrated efficacy in the adjunctive treatment of patients with refractory
partial epilepsy. Further investigation of the efficacy of
tiagabine is expected to provide a clearer definition of its place in the treatment of
epilepsy and its relative merits in relation to other
antiepileptic drugs.