OBJECTIVES: To explore the association between antiepileptic drug (AED) use and risk of suicide attempt (SA) in adults, taking account of psychiatric and neurological condition. METHODS: A case-control study was performed in France nationwide between June 2008 and September 2012. Cases were adults patients with one incident episode of suicide attempt requiring hospitalization for at least 12 hours and occurring within the previous month and with no other episode in the 12 months preceding recruitment (n=506). Controls were patients without history of suicide attempt, seen by a general practitioner (n=2829), and matched to SA cases on age and sex. Information on AED use, socioeconomics, lifestyle and personal medical history was collected by the psychiatrist for cases or by the physician for controls. Data on drug exposure was self-reported by participants through standardized patient telephone interviews. The association between AED use (all AEDs) and risk of suicide attempt was explored using logistic conditional regression and adjusted analyses after stratification on depression and neurologic status. RESULTS: There was a crude association between AED use in the 12 months preceding the index date and risk of suicide attempt (Odds Ratio [OR], 3.1; 95% confidence interval [CI], 2.1 to 4.5). In patients with current and/or past depression, AED use was associated with risk of suicide attempt, but this was no longer the case when clonazepam was excluded from the group of AEDs (OR, 0.9; 95% CI, 0.5-1.7). In patients with epilepsy, migraine or chronic neuropathic pain, no significant association was found between AED use and risk of suicide attempt (OR, 1.3; 95% CI, 0.6-2.8). CONCLUSIONS: The association observed between AEDs and SA is explained by underlying psychiatric or neurological conditions.