Topiramate monotherapy as broad-spectrum antiepileptic drug

Objective: To explore seizure outcomes and tolerability of topiramate (TPM) in mono- or conversion to monotherapy in patients with recently diagnosed epilepsy (epilepsy duration ≤3 years).

Methods: Prospective, open label, single arm, multicentre phase IV clinical trial (TOP-GER-5). Patients ≥18 years were followed for 28 weeks. Doses of TPM and concomitant antiepileptic drugs could be adjusted individually. Seizure frequency and adverse events were documented at each visit.

Results: The ITT population consisted of 191 patients (56% male, mean age overall 39.7±15.9 years). 39% started topiramate as initial monotherapy and 70% reached monotherapy at endpoint. 92.2% experienced at least one epileptic seizure during the 12 week retrospective baseline. Median trial duration was 28 weeks. 29.8% discontinued the trial prematurely. Median daily dose at endpoint was 100mg/day TPM. Mean seizure frequency decreased from 1.7±3.9 per 4 weeks at baseline to 1.1±4.5at endpoint (p<0.001 vs. baseline). 51.8% were seizure free at endpoint and 64.4% were seizure free for at least 12 weeks. Efficacy of treatment was rated as at least good in 71% of patients. Bodyweight decreased from 77.3kg±15.8 to 74.6kg±16.1at endpoint (p<0.001) which was associated with a decrease in mean systolic blood pressure by 2.5mmHg (p<0.05). Treatment related adverse events were reported in 40% of patients. AE ≥5% were paraesthesia (32%), fatigue (15%), concentration difficulties (9%), vertigo (8%), weight loss (8%), nausea (6%), headache (7%).

Conclusion: In patients with recent onset epilepsy, treatment with topiramate was well tolerated and associated with a high seizure freedom rate.