EffectofCitalopramonAgitationinAlzheimerDisease The CitAD Randomized Clinical Trial

IMPORTANCE Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory. OBJECTIVE The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety,cognitive safety, and tolerability. RESULTS Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was −0.93 (95% CI, −1.80 to −0.06),P =. 04.ResultsfromthemADCS-CGICshowed40%ofcitalopramparticipants having moderate or marked improvement from baseline compared with 26% of placebo recipients, with estimated treatment effect (odds ratio (OR) of being at or better than a given CGIC category) of 2.13 (95% CI, 1.23-3.69),P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (−1.05 points; 95% CI, −1.97 to −0.13;P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1;P = .01) were seen in the citalopram group.