CNS Drugs

, Volume 33, Issue 1, pp 17–29 | Cite as

Impact of Antidepressant Use on the Trajectory of Alzheimer’s Disease: Evidence, Mechanisms, and Therapeutic Implications

  • Rita KhouryEmail author
  • George T. Grossberg
Review Article


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.


Compliance with Ethical Standards


No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

RK has no conflicts of interest. GTG is a consultant for Acadia, Alkahest, Allergan, Avanir, Axovant, BioXcel, GE, Genentech, Lundbeck, Novartis, Otsuka, Roche, and Takeda; has received research support from Janssen, Roche, and the National Institutes of Health (NIH); and has served on a speaker’s bureau for Acadia and on safety monitoring committees for EryDel, Merck, and Newron.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Division of Geriatric PsychiatrySt. Louis University School of MedicineSt. LouisUSA

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