Is citalopram useful in the management of agitation in patients with Alzheimer disease?

Citalopram reduces agitation but may worsen cognitive impairment in Alzheimer disease

Bottom Line

Citalopram (Celexa; up to 30 mg daily, as tolerated) significantly reduces symptoms of agitation in patients with Alzheimer disease. However, the use of rescue lorazepam for agitation was not significantly reduced with the use of citalopram so the clinical significance of this improvement may be minimal. In addition, patients given citalopram showed significantly worsening cognitive impairment than patients given placebo. (LOE = 1b)

Reference

Porsteinsson AP, Drye LT, Pollock BG, et al, for the CitAD Research Group. Effect of citalopram on agitation in Alzheimer disease. The CitAD randomized clinical trial. JAMA 2014;311(7):682-691.

Study Design Randomized controlled trial (double-blinded) Funding Government
Setting Outpatient (specialty) Allocation Concealed

Synopsis

The optimal management of agitation in patients with Alzheimer disease remains uncertain. These investigators identified 186 adults with probable Alzheimer disease based on standard international criteria and Mini-Mental State Examination (MMSE) scores from 5 to 28 with physician-determined clinically significant agitation. The average age of the patients was 78.5 years and all had dementia for at least 5 years. Approximately two-thirds of the patients also took cholinesterase inhibitors and approximately 40% took memantine. Exclusion criteria included major depressive disorder or psychosis requiring antipsychotic treatment. Patients randomly received (concealed allocation assignment) citalopram (starting dose = 10 mg per day, with titration as tolerated to a target dose of 30 mg per day over 3 weeks) or matched placebo. Lorazepam and trazodone served as rescue medications for significant agitation or sleep disturbance. Individuals masked to treatment group assignment assessed outcomes using validated neurobehavioral rating scales and scoring tools. Complete follow-up occurred for 90% of patients at 9 weeks. Of these, 80% remained on treatment. Using intention-to-treat analysis, patients taking citalopram showed significantly improved scores (correlating with fewer signs and symptoms of agitation) than those taking placebo (mean score for the citalopram group = 4.1 vs mean score for the placebo group = 5.4; range = 0-18, with higher scores indicating more severe symptoms). Results from a scoring tool that evaluates overall clinician impression of global function showed that 40% of citalopram-treated patients had moderate or marked improvement from baseline severity compared with 26% of patients taking the placebo (number needed to treat = 7; 95% CI, 4-127). No differences occurred between the 2 treatments groups in the use of rescue lorazepam. Regarding adverse effects, MMSE results showed significant cognitive worsening in patients taking citalopram, and both falls and upper respiratory tract infections were also noted more often in the citalopram group.

David Slawson, MD
Director of Information Sciences
University of Virginia Health System
Charlottesville, VA

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