Tiagabine: a new therapeutic option for people with intellectual disability and partial epilepsy

Tiagabine exerts its antiepileptic drug (AED) activity by selectively inhib iting the uptake of gamma-aminobutyric acid (GABA) onto the transporter mol ecules, and thus, increasing extracellular concentrations of GABA in the br ain. The absorption and elimination of tiagabine follow linear pharmacokine tics. Tiagabine is metabolized by hepatic cytochrome P450 enzymes and enzym e-inducing AEDs increase tiagabine clearance by 50-65%. Tiagabine has shown no clinically important interactions with other drugs, including oral cont raceptives. In the perforant pathway stimulation model of status epilepticu s, tiagabine reduced the seizure number and severity, and also prevented th e loss of pyramidal cells in the hippocampus as well as alleviated impairme nt of the spatial memory impairment associated with hippocampal damage. Tia gabine has both antiepileptogenic and anticonvulsant effects in the kindlin g model of epilepsy. Based on the data from the short- and long-term add-on studies, tiagabine is effective adjunctive therapy for all partial seizure types in adolescents and adults. Conversion to tiagabine monotherapy has b een also possible in substantial amount of patients with partial seizures i n three trials. Tiagabine is generally well-tolerated. The most common adve rse events in controlled studies involve the central nervous system; for ex ample, dizziness, asthenia, nervousness, tremor, depressed mood and emotion al lability. Special safety analyses with formal neuropsychological testing suggest that tiagabine does not adversely affect cognition or mood. Tiagab ine represents an important new therapeutic option for patients with treatm ent-refractory partial seizures. The role of tiagabine in the management of partial epilepsy of patients with intellectual disability is especially em phasized since tiagabine has a low side-effect profile in the cognitive are a.