Topiramate in refractory epilepsy: A prospective observational study

Purpose: This prospective observational study explored the efficacy and tol erability of topiramate (TPM) in patients with refractory epilepsy attendin g a single outpatient clinic. Methods: One hundred seventy patients (82 men, 88 women, aged 18-75 years) with refractory localization-related (n = 134) or idiopathic generalized ep ilepsy (n = 36) were started on adjunctive TPM using a standard titration s chedule. TPM was introduced after a 3-month prospective baseline, and doses were adjusted according to clinical response. End points were seizure free dom for 6 months, greater than or equal to 50% seizure reduction for 6 mont hs compared with baseline at the highest tolerated TPM dose (responder), or discontinuation of TPM because of side effects, lack of efficacy, or both. Results: Thirty-nine (23%) patients were seizure-free, and 80 (47%) more pa tients had a useful therapeutic response. Thirteen seizure-free patients an d 16 responders took 100 mg of TPM daily or less. TPM was discontinued in 5 1 (30%) patients. The most common side effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Concomitant antiepileptic drugs (AEDs) were stopped in 30 patients. Twelve were established on TPM monotherapy, eight of whom remained seizure-free. Final TPM doses and concentrations varied widely among the three outcome gr oups. Conclusions: TPM was efficacious as add-on and monotherapy in patients with refractory partial and generalized seizures in everyday clinical use. A go od response was obtained in many patients with TPM doses substantially lowe r than those studied in regulatory clinical trials. The wide variation in d ose-response and dose-toxicity relationships may reflect different neurobio logies causing refractory epilepsy and differential efficacy of AED combina tions.