Efficacy and Safety of Escitalopram and Citalopram for Agitation in Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background

Agitation is a frequent and distressing neuropsychiatric symptom in patients with Alzheimer’s disease (AD), often leading to increased caregiver burden, institutionalization, and healthcare costs. While antipsychotics are commonly prescribed, their use is limited by safety concerns. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram and escitalopram, have emerged as alternative treatments with a more favorable safety profile. This study aimed to evaluate the efficacy and safety of these agents in the management of agitation in AD.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing citalopram or escitalopram with placebo or other pharmacological treatments in older adults with AD and clinically defined agitation. Primary outcomes included changes in agitation severity, assessed by the Neuropsychiatric Inventory–Clinician Rating (NPI-C) and the Neurobehavioral Rating Scale (NBRS). Secondary outcomes included cognitive function (MMSE), anxiety symptoms, and adverse events. Standardized mean difference (SMD) and risk ratio (RR) were pooled using a random-effects model.

Results

Four RCTs comprising 502 patients were included. Pooled analysis showed no significant improvement in agitation severity (SMD –0.67; 95% CI –2.58, 1.25; I² = 98.3%) or cognitive outcomes (SMD 2.43; 95% CI –2.55, 7.41). Rates of serious adverse events (RR 0.85; 95% CI 0.50, 1.45) and treatment discontinuation (RR 1.05; 95% CI 0.80, 1.37) were similar between groups. However, SSRI use was associated with an increased risk of falls (RR 1.78; 95% CI 1.15, 2.75; I² = 0%).

Conclusion

Escitalopram and citalopram do not significantly reduce agitation in AD but are generally well tolerated. Increased fall risk warrants cautious clinical use.

Registration PROSPERO protocol number

CRD420251055237.