The present study determines whether treatment with escitalopram compared with placebo could lower CSF β-amyloid 42 (Aβ42) levels.

Serotonin signaling is known to suppress Aβ42 in animal models of Alzheimers disease (AD) and young, healthy humans. This prospective study in older adults examined the dose and treatment duration effects of escitalopram.

This study used lumbar punctures to sample CSF levels before and after a course of escitalopram treatment, and assigned cognitively normal older adults (n = 114) to placebo, 20 mg escitalopram × two weeks, 20 mg escitalopram × eight weeks, or 30 mg escitalopram × eight weeks. It used CSF sampled pretreatment and posttreatment and within-subject percent change in Aβ42 as the primary outcome in subsequent analyses.

The study found a 9.4% greater reduction in CSF Aβ42 in escitalopram-treated compared with placebo-treated groups. Positive baseline Aβ status (CSF Aβ42 levels <250 pg/mL) showed an association with smaller Aβ42 reduction compared with negative baseline amyloid status (CSF Aβ42 levels >250 pg/mL).

This study shows that Short-term longitudinal doses of escitalopram decrease CSF Aβ42 in cognitively normal older adults, the target group for AD prevention.

Sheline YI, B. Snider J, Beer JC, et al., Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: A controlled clinical trial. Neurology. 2020, 95 (19): e2658-e2665. DOI: 10.1212/WNL.0000000000010725