Abstracts

Rationale: Little is known about the comparative efficacy and tolerability of modern antiepileptic agents when used as monotherapy in newly-diagnosed epilepsy. We have undertaken a pragmatic, randomised, open-label study of levetiracetam (LEV), topiramate (TPM), and lamotrigine (LTG) in people with newly-diagnosed epilepsy attending two specialist epilepsy centres in Glasgow, Scotland. Methods: A total of 251 patients (143 male; median age 34 years, range 16-82 years) with new-onset epilepsy were randomised to receive open-label LEV (n=81), TPM (n=85) or LTG (n=85), irrespective of seizure type or epilepsy syndrome. There were no statistically significant differences among treatment groups in multiple demographic variables at baseline, including gender, age, epilepsy type, time since last seizure, and total number or monthly frequency of pre-treatment seizures. Initial daily target doses were 1000mg LEV, 100mg TPM, and 150mg LTG, achieved by titration over 2, 4, and 6 weeks, and adjustable thereafter according to clinical effect. The primary outcome measures in this analysis are retention on treatment and seizure-freedom at 6 weeks, 6 months, and 12 months after starting treatment. Seizure freedom was defined as the absence of any further seizures after taking the first drug dose. Results: A total of 92.4% of patients remained on LEV at 6 weeks after starting treatment, compared with 86.4% on TPM and 90.5% on LTG. Retention at 6 months was 74.7% LEV, 66.7% TPM and 70.2% LTG. At 12 months, 51.9% of patients remained on LEV, compared with 51.9% on TPM, and 51.2% on LTG. There were no significant differences in retention at any of the time points investigated. Using a per-protocol analysis, 69.9% of LEV patients were seizure-free at 6 weeks, compared with 48.6% on TPM (χ²=6.719, p=0.01) and 44.7% on LTG (χ²=9.593, p=0.002). At 6 months, 52.5% of patients remaining on LEV were seizure-free, compared with 42.6% on TPM (χ²=1.12, p=0.29) and 35.6% on LTG (χ²=3.438, p=0.06). At 12 months, 48.8% of LEV patients were seizure-free, compared with 40.5% on TPM (χ²=0.579, p=0.447) and 32.6% on LTG (χ²=2.293, p=0.13). Conclusions: There were no differences in short- or longer-term retention on treatment amongst LEV, TPM and LTG. In terms of seizure freedom, the early advantage of LEV at 6 weeks after starting treatment may be explained by a more rapid titration to therapeutic dose but this was diminished during longer-term follow-up. These data suggest there is little to choose between the effectiveness of modern monotherapies in newly-diagnosed epilepsy.