Impact of SSRI Therapy on Risk of Conversion From Mild Cognitive Impairment to Alzheimer's Dementia in Individuals With Previous Depression

Am J Psychiatry. 2018 Mar 1;175(3):232-241. doi: 10.1176/appi.ajp.2017.17040404. Epub 2017 Nov 28.


Objective: Depression is associated with an increased risk of Alzheimer's disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer's dementia.

Method: Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer's Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates.

Results: In MCI patients with a history of depression, long-term SSRI treatment (>4 years) was significantly associated with a delayed progression to Alzheimer's dementia by approximately 3 years, compared with short-term SSRI treatment, treatment with other antidepressants, or no treatment and compared with MCI patients without a history of depression. No differences in CSF biomarker levels were observed between treatment groups.

Conclusions: Long-term SSRI treatment may delay progression from MCI to Alzheimer's dementia.

Keywords: Dementia-Alzheimer-s Disease; Dementia-Other; Diagnosis And Classification; Geriatric Psychiatry; Psychotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / etiology
  • Alzheimer Disease / prevention & control*
  • Citalopram / therapeutic use*
  • Cognitive Dysfunction / complications*
  • Cognitive Dysfunction / drug therapy
  • Depression / complications
  • Depression / drug therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*


  • Serotonin Uptake Inhibitors
  • Citalopram