Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults
Yvette I. Sheline, B. Joy Snider, Joanne C. Beer, Darsol Seok, Anne M. Fagan, Raymond F. Suckow, Jin‐Moo Lee, Teresa Waligórska, Magdalena Korecka, Irem Aselcioglu, John C. Morris, Leslie M. Shaw, John R. Cirrito
Abstract
<h3>Objective</h3> To determine whether treatment with escitalopram compared with placebo would lower CSF β-amyloid 42 (Aβ<sub>42</sub>) levels. <h3>Rationale</h3> Serotonin signaling suppresses Aβ<sub>42</sub> 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. <h3>Methods</h3> 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<sub>42</sub> was used as the primary outcome in subsequent analyses. <h3>Results</h3> An overall 9.4% greater reduction in CSF Aβ<sub>42</sub> 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 Aβ<sub>42</sub> levels <250 pg/mL) was associated with smaller Aβ<sub>42</sub> 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 Aβ<sub>42</sub> levels >250 pg/mL). <h3>Conclusions</h3> Short-term longitudinal doses of escitalopram decreased CSF Aβ<sub>42</sub> in cognitively normal older adults, the target group for AD prevention. <h3>Clinicaltrials.gov identifier</h3> NCT02161458. <h3>Classification of evidence</h3> This study provides Class II evidence that for cognitively normal older adults, escitalopram decreases CSF Aβ<sub>42</sub>.