Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study

Background: To investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs. Method: We conducted a case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2013. A total of 863 patients with epilepsy and 3,452 controls were included. The dose of ADs was categorized according to the cumulative defined daily dose (cDDD). The risk of epilepsy was assessed using conditional logistic regression analysis. Results: Compared with cDDD < 90, ADs exposure with cDDD > 365 (odds ratio [OR]: 1.37, 95% confidence interval [CI]:1.12–1.68) was associated with an increased risk of epilepsy, but not for those with cDDD 90–365 (OR: 1.07,95% CI: 0.87–1.30) after adjustment for several comorbidities and indications of ADs use. Other identified risk factors include cerebrovascular disease, traumatic brain injury, and central nervous system infection. Subgroup analysis of individual ADs showed that escitalopram (OR: 1.93, 95% CI: 1.12–3.31), venlafaxine (OR: 1.62, 95% CI: 1.13–2.31), mirtazapine (OR: 1.56, 95% CI: 1.00–2.43), paroxetine (OR: 1.44, 95% CI: 1.08–1.94), and fluoxetine (OR: 1.25, 95% CI: 1.01–1.56) had a significantly higher risk of epilepsy. Sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion did not show any proconvulsant effects. Conclusions: The study found an increased risk of epilepsy among patients who were exposed to any ADs, particularly longer-term users. Given the nature of observational studies with residual bias, interpretation should be cautious.