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

Objective: To determine whether treatment with escitalopram compared with placebo would lower CSF β-amyloid 42 (Aβ ₄₂ ) levels.
Rationale: Serotonin signaling suppresses Aβ ₄₂ 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.
Methods: 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 Aβ ₄₂ was used as the primary outcome in subsequent analyses.
Results: An overall 9.4% greater reduction in CSF Aβ ₄₂ was found in escitalopram-treated compared with placebo-treated groups ( p < 0.001, 95% confidence interval [CI] 4.9%-14.2%, d = 0.81). Positive baseline Aβ status (CSF Aβ ₄₂ levels <250 pg/mL) was associated with smaller Aβ ₄₂ reduction ( p = 0.006, 95% CI -16.7% to 0.5%, d = -0.52) compared with negative baseline amyloid status (CSF Aβ ₄₂ levels >250 pg/mL).
Conclusions: Short-term longitudinal doses of escitalopram decreased CSF Aβ ₄₂ in cognitively normal older adults, the target group for AD prevention.
Clinicaltrialsgov Identifier: NCT02161458.
Classification of Evidence: This study provides Class II evidence that for cognitively normal older adults, escitalopram decreases CSF Aβ ₄₂ .
(© 2020 American Academy of Neurology.)