Valproate was more effective than lamotrigine and better tolerated than topiramate in generalized or unclassified epilepsy.

M e t h o d s Design: Randomized controlled trial (Standard and New Antiepileptic Drugs [SANAD] trial, Arm B). Allocation: Concealed.* Blinding: Unblinded.* Follow-up period: Up to 6 years. Setting: Hospital-based outpatient clinics in the United Kingdom. Patients: 716 patients (mean age 23 y, 60% men) who had ≥ 2 clinically definite, unprovoked epileptic seizures in the past year and were recommended to take VAL over carbamazepine by the recruiting clinician. Exclusion criteria were age ≤ 4 years, acute symptomatic seizures (including febrile seizures), history of progressive neurologic disease, and contraindications to treatment. Intervention: VAL (n = 238), LTG (n = 239), or TPM (n = 239). Outcomes: Treatment failure (i.e., stopping drug because of inadequate seizure control, intolerable side effects, or both or addition of other antiepileptic drugs) and 1-year remission. Secondary outcomes included 2-year remission and time to first seizure. Patient follow-up: 97% (intention-to-treat analysis).