Purpose Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. Methods Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). Results Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95% CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95% CI, 1.0-2.5), but unmeasured confounding was suspected. Conclusions Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level. Copyright (C) 2017 John Wiley & Sons, Ltd.