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

Objective To determine whether compared with placebo, treatment with escitalopram (ESC) would lower CSF (CSF) amyloid beta 42 (Aβ42) levels. Rationale Serotonin signaling suppresses Aβ42 in animal models of Alzheimer9s disease (AD) and young healthy humans. In a prospective study in older adults, we examined dose and treatment duration effects of ESC. Methods Using lumbar punctures (LPs) to sample CSF levels before and after a course of ESC treatment, cognitively normal older adults (n = 114) were assigned to either: placebo; 20 mg ESC × 2 weeks; 20 mg ESC × 8 weeks or 30 mg ESC × 8 weeks with CSF sampled pre- and post-treatment and within-subject percent change in Aβ42 was used as the primary outcome in subsequent analyses. Results An overall 9.4% percentage point greater reduction in CSF Aβ42 was found in ESC treated compared with placebo treated groups (p 250 pg/mL). Conclusions Short-term longitudinal doses of ESC decreased CSF Aβ42 in cognitively normal older adults, the target group for AD prevention. Classification of evidence This study provides Class II evidence that for cognitively normal older adults, ESC decreases CSF Aβ42. Clinical trial identifier NCT02161458.