Research Summary

Study: Escitalopram Ineffective for Agitation in Alzheimer Dementia, May Pose Cardiac Risks

Anthony Calabro, MA

Key Highlights

  • Escitalopram did not significantly improve agitation in Alzheimer dementia compared with placebo.
  • QT prolongation was observed in the escitalopram group, indicating cardiac risk.
  • The trial sample was smaller than planned, limiting statistical power.

Agitation is a common and distressing symptom in individuals with AD, often leading to increased caregiver burden and institutionalization. Although citalopram has shown efficacy in treating agitation, its use is limited due to cognitive side effects and cardiac conduction risks. The authors hypothesized that escitalopram would retain efficacy with fewer adverse effects.

This double-masked, placebo-controlled trial enrolled participants from 27 community-based centers across the United States. Eligible participants had a diagnosis of AD, Mini-Mental State Examination Telephone scores between 3 and 20, and clinically significant agitation. All underwent a psychosocial intervention (PSI) before randomization. Nonresponders were assigned in a 1:1 ratio to receive either escitalopram (up to 15 mg/day) or placebo for 12 weeks, while continuing PSI. The primary outcome was the proportion of participants showing clinically significant improvement in agitation at 12 weeks.

A total of 173 participants were randomized (84 to escitalopram and 89 to placebo). The mean age was 78.4 years (±8.7), and 52% of the participants were men. At week 12, the unadjusted risk difference in clinical improvement between the escitalopram and placebo groups was 0.08 (95% CI, -0.21 to 0.06), indicating no statistically significant treatment effect. Notably, escitalopram was associated with QT interval prolongation, suggesting potential cardiac risks.

The authors noted that they anticipated a larger randomized sample. Still, they found that escitalopram did not effectively treat agitation in AD.

“Although the randomized sample was smaller than planned, escitalopram was not effective in treating agitation in AD and was associated with cardiac conduction delays,” the authors concluded. “Clinicians need to be cautious in recommending escitalopram as an alternative to citalopram for this condition.”

Reference
Rajji TK, Baksh SN, Shade DM, et al. Escitalopram for agitation in Alzheimer’s dementia: a randomized controlled phase 3 trial. Nat Med. 2025;31:1586–1591. doi:10.1038/s41591-024-03050-w