Long‐Term Safety of Tiagabine

Summary: Tiagabine (TGB) is now registered in >20 countries, and the total number of treated patients approaches 90,000. Short‐term safety data were derived mainly from five placebo‐controlled, add‐on studies in adults with therapy‐resistant partial epilepsy, and two conversion to TGB monotherapy studies. Central nervous system (CNS)‐related adverse effects, most frequently dizziness, were common with TGB treatment during the titration period; the risk became similar to placebo rates during fixed‐dose periods. Other adverse events that were more frequent in TGB‐ than in placebo‐treated patients were asthenia, nervousness, tremor, concentration difficulties, depressive mood, and language problems. TGB doses should be titrated slowly and taken with food to avoid rapid increases in plasma concentrations, thus minimizing the risks of adverse events. Overall, >2,500 patients have been exposed to TGB during clinical trials, with 1,274 patients treated >12 months, the majority of whom received TGB 24–60 mg/day. No idiosyncratic reactions have been linked to the use of TGB, and no abnormalities in hematology or common chemistry values were reported. In all the epilepsy studies combined, 21% of patients discontinued treatment because of adverse events, usually during the first 6 months of treatment. No adverse effects on cognitive abilities were detected when the neuropsychological effects of TGB add‐on therapy and monotherapy were evaluated. TGB does not appear to cause an excess risk of psychosis or increase the incidence of status epilepticus or spike/wave discharges. No evidence of a relationship between visual field constriction and TGB treatment was found in a study of 15 patients converted to TGB monotherapy (mean dose, 22 mg/day; mean duration, 2.5 years) who had a full ophthalmologic evaluation. In conclusion, the characteristics of TGB in the management of partial epilepsy are enhanced by its favorable side‐effect profile in the cognitive area.