Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults: A controlled clinical trial.

Abstract

To determine whether treatment with escitalopram compared with placebo would lower CSF β-amyloid 42 (Aβ₄₂) levels. Serotonin signaling suppresses Aβ₄₂ in animal models of Alzheimer disease (AD) and young healthy humans. In a prospective study in older adults, we examined dose and treatment duration effects of escitalopram. Using lumbar punctures to sample CSF levels before and after a course of escitalopram treatment, cognitively normal older adults (n = 114) were assigned to placebo, 20 mg escitalopram × 2 weeks, 20 mg escitalopram × 8 weeks, or 30 mg escitalopram × 8 weeks; CSF sampled pretreatment and posttreatment and within-subject percent change in Aβ₄₂ was used as the primary outcome in subsequent analyses. An overall 9.4% greater reduction in CSF Aβ₄₂ was found in escitalopram-treated compared with placebo-treated groups (<i>p</i> < 0.001, 95% confidence interval [CI] 4.9%-14.2%, <i>d</i> = 0.81). Positive baseline Aβ status (CSF Aβ₄₂ levels <250 pg/mL) was associated with smaller Aβ₄₂ reduction (<i>p</i> = 0.006, 95% CI -16.7% to 0.5%, <i>d</i> = -0.52) compared with negative baseline amyloid status (CSF Aβ₄₂ levels >250 pg/mL). Short-term longitudinal doses of escitalopram decreased CSF Aβ₄₂ in cognitively normal older adults, the target group for AD prevention. NCT02161458. This study provides Class II evidence that for cognitively normal older adults, escitalopram decreases CSF Aβ₄₂.