Drug Evaluation Central & Peripheral Nervous Systems: Tiagabine: current status and potential clinical applications

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Abstract
The management of patients with epilepsy remains a challenge for clinicians. Partial-onset seizures are particularly refractory to antiepileptic drug (AED) therapy. Many patients require multiple AEDs for maximal seizure control and drug-drug interactions often complicate chronic therapy. Consequently, for those patients who have been unable to function up to their abilities because of seizures or medication side-effects, the introduction of new anticonvulsant medications has brought new hope. Tiagabine hydrochloride (TGB), which selectively inhibits γ-aminobutyric acid uptake in the central nervous system, has a remarkably specific and novel mechanism of action that is unique among AEDs. TGB exerts an anticonvulsant effect in a wide range of animal seizure models, has no clinically-relevant effect on hepatic metabolic processes or serum levels of other AEDs, does not displace highly protein-bound drugs, has no clinically-significant effects on laboratory values, and has not been shown to have any clinically-important interactions with common non-AEDs. TGB has linear, predictable pharmacokinetics which do not vary significantly with age and is safe and well-tolerated in patients with long-standing, medically-refractory partial-onset epilepsy. Adverse effects are usually mild to moderate in severity, and almost always resolve without medical intervention. Controlled studies of patients on AED therapy show that add-on TGB is effective for partial seizures with and without secondary generalisation in dosages ranging from 32 - 56 mg. Conversion to TGB monotherapy can be achieved in patients with medically-refractory epilepsy and results of paediatric studies are encouraging.