Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Epilepsy Behav. 2023 Mar;140:109102. doi: 10.1016/j.yebeh.2023.109102. Epub 2023 Feb 4.
To investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs.
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.
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.
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.
本研究旨在探讨抗抑郁药（ADs）暴露与 ADs 暴露者癫痫发病风险的相关性。
本研究采用台湾全民健康保险研究数据库，于 1998 年至 2013 年期间开展了一项病例对照研究。共纳入 863 例癫痫患者和 3452 例对照。根据累积限定日剂量（cDDD）对 ADs 剂量进行分类。采用条件 logistic 回归分析评估癫痫发病风险。
与 cDDD＜90 相比，cDDD＞365 时 ADs 暴露（比值比[OR]：1.37，95%置信区间[CI]：1.12-1.68）与癫痫发病风险增加相关，但 cDDD 为 90-365 时 ADs 暴露（OR：1.07，95%CI：0.87-1.30）无此相关性（经多种合并症和 ADs 使用适应证校正后）。其他确定的危险因素包括脑血管疾病、创伤性脑损伤和中枢神经系统感染。ADs 单药治疗亚组分析显示，艾司西酞普兰（OR：1.93，95%CI：1.12-3.31）、文拉法辛（OR：1.62，95%CI：1.13-2.31）、米氮平（OR：1.56，95%CI：1.00-2.43）、帕罗西汀（OR：1.44，95%CI：1.08-1.94）和氟西汀（OR：1.25，95%CI：1.01-1.56）癫痫发病风险显著增加。舍曲林、氟伏沙明、西酞普兰、度洛西汀、米那普仑和安非他酮无致痫作用。
本研究发现 ADs 暴露者癫痫发病风险增加，尤其是长期使用者。鉴于观察性研究存在残余偏倚的性质，解读时应谨慎。
