Division of Geriatric Psychiatry, St. Louis University School of Medicine, 1438 S Grand Blvd, St. Louis, MO, 63104, USA.
CNS Drugs. 2019 Jan;33(1):17-29. doi: 10.1007/s40263-018-0590-9.
The relationship between antidepressants and Alzheimer's disease (AD) is very complex, and the literature is mixed regarding the effect of these medications on the trajectory of the disease. This paper reviews findings from relevant clinical studies that have assessed the impact of antidepressants on AD onset and disease progression. To date, these medications seem to attenuate the risk of developing the disease without affecting the rate of progression. However, most evidence stems from observational studies that are subject to methodological bias. Serotonergic antidepressants are thought to affect AD pathophysiology by reducing β-amyloid (Aβ) plaque formation and promoting hippocampal neurogenesis. However, the mechanisms underlying their effect need to be examined further, especially in humans. Moreover, more robust clinical studies in terms of design (randomized controlled trials) and longer duration of follow-up are needed. Variables, including depression timeline/onset and its clinical course, apolipoprotein E4 (APOE4) genotype status, sex, dose/duration of antidepressant treatment, and AD biomarkers need to be incorporated in future trials to better elucidate the effect of antidepressants on AD risk.
抗抑郁药与阿尔茨海默病（AD）之间的关系非常复杂，关于这些药物对疾病轨迹的影响，文献报道不一。本文综述了评估抗抑郁药对 AD 发病和疾病进展影响的相关临床研究结果。迄今为止，这些药物似乎可以降低发病风险，而不影响疾病进展速度。然而，大多数证据来自于易受方法学偏倚影响的观察性研究。血清素能抗抑郁药被认为通过减少β-淀粉样蛋白（Aβ）斑块形成和促进海马神经发生来影响 AD 的病理生理学。然而，需要进一步研究其作用机制，尤其是在人类中。此外，还需要在设计（随机对照试验）和随访时间方面进行更有力的临床研究。未来的试验需要纳入变量，包括抑郁的时间轴/发病和临床过程、载脂蛋白 E4（APOE4）基因型状态、性别、抗抑郁药治疗的剂量/持续时间以及 AD 生物标志物，以更好地阐明抗抑郁药对 AD 风险的影响。
