OBJECTIVE: To determine the pattern of treatment response in patients with idiopathic generalized epilepsy (IGE) and whether routinely assessed clinical and neurophysiological parameters allow predicting response to lamotrigine, levetiracetam, or valproic acid.

METHODS: In 328 adult patients with IGE, demographic data, imaging, EEG data, current and prior antiepileptic treatment, treatment outcome, and side effects were analyzed from the patients' medical files and patient interviews.

RESULTS: Seizure freedom with acceptable side effects at the first attempt was achieved in 61 (18.6%) patients. One hundred four (31.7%) patients tried ≥3 antiepileptic drugs before achieving seizure control at the last follow-up. Lamotrigine, levetiracetam, and valproic acid showed differential response rates (39.8% vs 47.5% vs 71.1%) that were most pronounced in patients with juvenile myoclonic epilepsy. The risk of having side effects was higher with valproic acid (23.7%) than with lamotrigine (10.4%) or levetiracetam (20.4%) treatment, contributing to the low retention rate of valproic acid (53.7%). Treatment resistance was associated with established risk factors. Multivariate analyses aiming at identifying clinical indicators for response to specific drugs did not reveal putative biomarkers when corrected for drug resistance.

CONCLUSION: Despite a high rate of seizure control, the chance of achieving seizure control and acceptable side effects at first attempt was low due to an inverse association of effectiveness and side effects of the 3 most commonly used drugs. Routinely assessed clinical parameters were not indicative for response to specific drugs.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with IGE, various clinical factors do not predict a response to specific antiepileptic drugs.