INTRODUCTIONThe use of antidepressants in major depressive disorder (MDD) has been reported to influence long‐term risk of Alzheimer's disease (AD) and AD‐related dementias (AD/ADRD), but studies are conflicting.METHODSWe used inverse probability weighted (IPW) Cox models with time‐varying covariates in a retrospective cohort study among midlife veterans with MDD within the US Veterans Affairs healthcare system from January 1, 2000 to June 1, 2022.RESULTSA total of 35,200 patients with MDD were identified. No associations were seen regarding the effect of being exposed to any antidepressant versus no exposure on AD/ADRD risk (events = 1,056, hazard ratio = 0.94, 95% confidence interval: 0.81 to 1.09) or the exposure to specific antidepressant classes versus no exposure. A risk reduction was observed for female patients in a stratified analysis; however, the number of cases was small.DISCUSSIONOur study suggests that antidepressant exposure has no effect on AD/ADRD risk. The association in female patients should be interpreted with caution and requires further attention.Highlights We studied whether antidepressant use was associated with future dementia risk. We specifically focused on patients after their first‐ever diagnosis of depression. We used IPW Cox models with time‐varying covariates and a large observation window. Our study did not identify an effect of antidepressant use on dementia risk. A risk reduction was observed in female patients, but the number of cases was small.

中文翻译：

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一项针对患有中年重度抑郁症的美国退伍军人的全国性回顾性研究中的抗抑郁药物暴露与长期痴呆风险

简介 据报道，在重度抑郁症 (MDD) 中使用抗抑郁药会影响阿尔茨海默病 (AD) 和 AD 相关痴呆 (AD/ADRD) 的长期风险，但研究结果相互矛盾。方法我们使用逆概率加权 (IPW)对 2000 年 1 月 1 日至 2022 年 6 月 1 日美国退伍军人事务部医疗保健系统内患有 MDD 的中年退伍军人进行的一项回顾性队列研究中，采用具有时变协变量的 Cox 模型。 结果 总共确定了 35,200 名 MDD 患者。暴露于任何抗抑郁药物与不暴露对 AD/ADRD 风险的影响（事件 = 1,056，风险比 = 0.94，95% 置信区间：0.81 至 1.09）或暴露于特定抗抑郁药物类别与不暴露之间没有关联。 。在分层分析中观察到女性患者的风险降低；然而，病例数量很少。讨论我们的研究表明，抗抑郁药暴露对 AD/ADRD 风险没有影响。女性患者中的相关性应谨慎解释并需要进一步关注。亮点 我们研究了抗抑郁药物的使用是否与未来患痴呆症的风险相关。 我们特别关注首次诊断出抑郁症的患者。 我们使用具有时变协变量和大观察窗口的 IPW Cox 模型。 我们的研究没有确定抗抑郁药的使用对痴呆风险的影响。 在女性患者中观察到风险降低，但病例数很少。