HealthDay News — The antidepressant citalopram (Celexa) combined with a psychosocial intervention may reduce agitation in patients with probable Alzheimer’s disease, but not without adverse cardiac and cognitive effects, according to researchers.

In a randomized clinical trial, patients assigned to the selective seratonin reuptake inhibitor (SSRI) citalopram, experienced significant reductions in agitation compared with those taking a placebo, Anton P. Porsteinsson, MD, from the University of Rochester in New York, and colleagues reported in the Journal of the American Medical Association.

But the medication was also associated with an increase in QT interval prolongation and, surprisingly, worsening of cognition, the researchers found.

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They enrolled 186 patients with probable Alzheimer’s disease and clinically significant agitation at eight academic centers from August 2009 to January 2013. Participants were assigned to psychosocial intervention plus either citalopram (n=94) or placebo (n=92) for nine weeks. Those in the intervention group had a citalopram starting dose of 10 mg per day with planned titration to 30 mg per day over three weeks based on response.

Compared with those who received placebo, participants who received citalopram showed significant improvement on both the 18-point Neurobehavioral Rating Scale agitation subscale (P=0.04) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC).

In terms of mADCS-CGIC scores, 40% of those in the citalopram group had moderate or marked improvement from baseline compared with 26% of placebo recipients, with an estimated treatment effect of 2.13 (P=0.01). The estimated treatment difference on the neurobehavioral agitation subscale (citalopram minus placebo) was −0.93 (P=0.04).

Caregiver distress fell significantly (P=0.02) after nine weeks for those looking after patients in the citalopram group, the researchers found.

However, citalopram use was associated with worsening of cognition – a 1.05-point worsening in scores on the Minim-Mental State Examination (P = 0.03) – and an 18.1 ms increase in QT interval (P= 0.01).

“The addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day,” the researchers concluded.

Despite these findings, Gary Small, MD, of the University of California Los Angeles, suggested that citalopram may still have a role in treating dementia-associated agitations in an accompanying editorial, but noted that “when and how to prescribe the drug [is] not straightforward.”

Although the current study was not adequately powered to determine the benefits of dosages below 30 mg per day, keeping the dosage lower than 20 mg per day may help manage adverse effects, the researchers suggested.

Small called for more research to study citalopram’s benefits, as well as the duration of adverse effects beyond the nine week period in the study by Porsteinsson et al, as well as dose ranges that influence mortality, QT prolongation and predictors of response.

As the study involved a convenience sample, the findings may not be generalizable to other settings, the researchers noted. Other limitations include short overall treatment duration, the lack of dose-ranging information and lack of participants with non-Alzheimer dementia.


  1. Porsteinsson AP et al. JAMA. 2014; 311(7): 682-691.
  2. Small GW. JAMA. 2014; 311(7): 677-678.

Disclosures: The study National Institute on Aging and the National Institute of Mental Health provided study funding. Porsteinsson disclosed relevant relationships with Avanir, Baxter, BMS, Elan, EnVivo, Genentech/Roche, Janssen Alzheimer Initiative, Merck, Pfizer, Toyama, Medivation, TransTech Pharma, Quintiles, Functional Neuromodulation, Forest and CME.