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Study identifies predictors of benefit, harm of citalopram for Alzheimer’s disease with agitation

Among individuals with Alzheimer’s disease with agitation, citalopram was more likely to benefit those with moderate agitation and lower levels of cognitive impairment, whereas those with more severe agitation and greater cognitive impairment were at higher risk for adverse responses.

“Trials of antidepressants have been conducted for treating depression in people with dementia and, more recently, agitation. Citalopram in particular showed equivalence to antipsychotics for inpatients and outpatients, but with differential adverse events,” Lon S. Schneider, MD, MS, of Keck School of Medicine of University of Southern California, Los Angeles, and colleagues wrote.

To identify individuals that benefited from citalopram treatment and those who did not, researchers assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study. Study participants with Alzheimer’s disease and clinically significant agitation (n = 186) were randomly assigned to receive citalopram or placebo for 9 weeks, with dosage titrated to 30 mg per day over the first 3 weeks. Five potential predictors of treatment outcome were assessed, including residency status (long-term care vs. outpatient), presence of psychosis, and severity of functional impairment, cognitive impairment, and agitation. Researchers used a two-stage multivariate method to identify the most likely predictors.

Study participants with the greatest predicted treatment effects favoring citalopram were more likely to live outside long-term care facilities, have milder cognitive impairment (Mini-Mental State Examination [MMSE] scores ranging from 21 to 28), have baseline Neurobehavioral Rating Scale agitation subscale scores ranging from 6 to 8, be within middle age range of 76 to 82 years, and had not used lorazepam at baseline.

Study participants with the greatest predicted treatment effect favoring placebo were more likely to live in long-term care, have moderate to severe cognitive impairment (MMSE scores of 20 or greater), have more severe baseline agitation (Neurobehavioral Rating Scale agitation subscale scores ranging from 9 to 14), to be in the youngest (47 to 75 years) or oldest (83 to 92 years) age ranges, and be treated with lorazepam.

“Given the clinical heterogeneity of agitation and aggression in patients with Alzheimer’s disease, it is likely that any effective therapy would benefit only a subset of patients with these behaviors,” the researchers wrote. “In our planned, protocol-specified analysis of this randomized controlled trial, we found no individual covariates that predicted positive outcomes with citalopram but did find that residence in long-term care was associated with a negative outcome with citalopram.” – by Amanda Oldt

Disclosure: Schneider reports receiving grants and clinical trials support from NIH, Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Merck, NIH, Novartis, Pfizer, and Roche and consultancy fees, including for data monitoring committees and adjudication committees, from Abbott, AbbVie, ACImmune, AstraZeneca, Baxter, Bristol-Myers Squibb, Elan, Eli Lilly, Forest Laboratories, Forum, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Merck, Merz, Novartis, Orion, Otsuka, Pfizer, Roche, Servier, Takeda, Toyama/FujiFilm, and Zinfandel. Please see the full study for a list of all other authors’ relevant financial disclosures.