Review of Controlled Trials of Gabitril (Tiagabine): A Clinician's Viewpoint

Summary: A recent problem for doctors has been the choice of which new antiepileptic drug (AED) to select for treatment of pharmacoresistant epilepsy. This article summarizes the clinical experience to date regarding the efficacy and safety of tiagabine (TGB; Gabitril) as adjunctive therapy in patients with partial-onset seizures. In its early Phase II development, TGB was evaluated in two multicenter pilot studies. Each had an open-label enrichment phase followed by a treatment phase with randomized, double-blind, two-period, cross-over phases. Between 24 and 50% of patients experienced reductions in seizure rates of ≥50%, depending on the type of partial seizure. In Phase III, three double-blind, parallel group, placebo-controlled adjunctive studies determined the efficacy of TGB in patients with refractory partial seizures. The first was a dose-response study employing doses of TGB-HCl of 16, 32 or 56 mg/day. Significant reductions in seizure rates were found with 32 and 56 mg/day. The second and third studies evaluated the efficacy of dosing TGB twice, three times, and four times daily, all of which showed similar efficacy. TGB efficacy in partial seizures was supported in several open trials, and no tolerance to efficacy was noted in long-term continuation studies. Tolerability was documented in all trials. Most adverse events were mild or moderate and transient, occurring during dose titration. They were clearly dose-related. No relevant changes in hematologic and biochemical tests, vital signs, or body weight were attributable to TGB. TGB appears to be an effective new drug for partial seizures with an acceptable safety profile.