Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer's disease

Int J Geriatr Psychiatry. 2016 Jul;31(7):731-9. doi: 10.1002/gps.4384. Epub 2015 Nov 9.

Abstract

Objectives: A series of preclinical studies have suggested that selective serotonin reuptake inhibitor antidepressants not only stimulate neurogenesis but also have neuroprotective effects. The present study primarily aimed to investigate whether escitalopram would decelerate the brain atrophy of patients with mild-to-moderate Alzheimer's disease (AD). We also assessed the effects of escitalopram on the cognitive function and neuropsychiatric symptoms of these participants.

Methods: Seventy-four probable AD patients without major depression were recruited from four dementia clinics of university hospitals and randomly assigned in a 1:1 ratio. Each group received 20 mg/day of escitalopram or placebo for 52 weeks. The primary outcome measures were the change rates of hippocampal and whole brain volume on magnetic resonance imaging for 52 weeks. The Alzheimer's Disease Assessment Scale-cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia (CSDD) were also applied.

Results: We did not find any significant differences in the changes of hippocampal or whole brain volume between the groups. Escitalopram showed significant beneficial effects on the CSDD score at 28 weeks compared with placebo (t = -2.17, df = 50.42, p = 0.035), but this finding did not persist throughout the study.

Conclusion: The findings of the present study do not support the role of escitalopram as a progression-delaying treatment for AD. However, the negative results of the present trial should be interpreted cautiously because of the relatively small sample size. Further large-scale escitalopram trials targeting the earlier stages of AD, even prodromal AD, are still needed. Copyright © 2015 John Wiley & Sons, Ltd.

Keywords: Alzheimer's disease; brain atrophy; clinical trial; escitalopram; magnetic resonance imaging; selective serotonin reuptake inhibitor.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Antidepressive Agents, Second-Generation / pharmacology
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Brain / drug effects*
  • Brain / pathology
  • Citalopram / therapeutic use*
  • Cognition / drug effects
  • Disease Progression
  • Double-Blind Method
  • Female
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*

Substances

  • Antidepressive Agents, Second-Generation
  • Neuroprotective Agents
  • Serotonin Uptake Inhibitors
  • Citalopram