Effect of selective serotonin reuptake inhibitors in Alzheimer's disease with comorbid depression: a meta-analysis of depression and cognitive outcomes

Drugs Aging. 2012 Oct;29(10):793-806. doi: 10.1007/s40266-012-0012-5.


Background: Comorbid depression is a leading neuropsychiatric complication in the Alzheimer's disease (AD) syndrome. In 2011, diagnostic criteria for AD were revised to include neuropsychiatric symptoms. It has been proposed that adding an antidepressant to existing treatment for AD could provide relief for not only depressive but also cognitive symptoms.

Objective: The aim was to quantitatively review published studies to examine the efficacy of selective serotonin reuptake inhibitor (SSRI)/serotonin-noradrenaline (norepinephrine) reuptake inhibitor (SNRI) therapy for alleviation of comorbid, diagnosed depression as well as cognitive decline in AD.

Methods: A search of electronic databases was performed. Studies were retained for analysis if SSRI/SNRI antidepressant therapy was compared with placebo among AD patients with comorbid depression. Effect-size (ES) estimates (Hedges' g) were calculated using Comprehensive Meta-Analysis software.

Results: From 598 examined studies, 12 SSRI studies met the inclusion criteria, and from these, only six met all criteria, among which five reported sufficient and consistent data to be included in the meta-analysis. Within a random effect model, ES estimates of the first and second nested global analyses were non-significant, non-heterogeneous and small to null at the endpoint for depression, favouring SSRIs, -0.06 and -0.10, respectively (p > 0.05). The ES for global cognition as measured by the Mini-Mental State Examination was negligible (ES = 0.001).

Conclusions: Current evidence does not support the efficacy of SSRI treatment for symptoms of comorbid depression in AD. However, studies differed in terms of criteria for diagnosis of depression, the compound tested and outcome measures for depression. These factors could account for the lack of a clear benefit for depression.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / physiopathology
  • Animals
  • Clinical Trials as Topic
  • Cognition / drug effects*
  • Comorbidity
  • Depression / epidemiology*
  • Humans
  • Serotonin Uptake Inhibitors / pharmacology*
  • Serotonin Uptake Inhibitors / therapeutic use


  • Serotonin Uptake Inhibitors