LAUSR

Objective To determine whether treatment with escitalopram compared with placebo would lower CSF β-amyloid 42 (Aβ42) levels. Rationale 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. 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 Aβ42 was used as the primary outcome in subsequent analyses. Results An overall 9.4% greater reduction in CSF Aβ42 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 Aβ42 levels <250 pg/mL) was associated with smaller Aβ42 reduction (p = 0.006, 95% CI −16.7% to 0.5%, d = −0.52) compared with negative baseline amyloid status (CSF Aβ42 levels >250 pg/mL). Conclusions Short-term longitudinal doses of escitalopram decreased CSF Aβ42 in cognitively normal older adults, the target group for AD prevention. Clinicaltrials.gov identifier NCT02161458. Classification of evidence This study provides Class II evidence that for cognitively normal older adults, escitalopram decreases CSF Aβ42.