Medication to Treat Agitation for Alzheimer Disease Shows Mixed Results

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Chicago – The use of the medication citalopram was associated with a reduction in agitation in patients with Alzheimer disease, although at the dosage used in the study, patients experienced mild cognitive and cardiac adverse effects that might limit the practical application of this medication at the dosage of 30 mg per day, according to a study in the February 19 issue of JAMA.

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Agitation, which is common in patients with Alzheimer disease, is persistent, difficult to treat, costly, and associated with severe adverse consequences for patients and caregivers. Pharmacologic therapies have proven inadequate and antipsychotic drugs continue to be widely used for this condition despite serious safety concerns, including increased risk of death, and uncertain efficacy, according to background information in the article. Citalopram, an antidepressant drug frequently used in older individuals, has been proposed as an alternative to antipsychotic drugs for agitation and aggression in dementia, yet there is limited evidence for its efficacy and safety.

Anton P. Porsteinsson, M.D., of the University of Rochester School of Medicine and Dentistry, Rochester, N.Y., and colleagues randomized 186 patients with probable Alzheimer disease without major depression and clinically significant agitation from 8 academic centers in the United States and Canada to receive citalopram (n = 94) or placebo (n = 92) for 9 weeks. Both groups received psychological counseling and assistance.

Treatment with citalopram 30 mg per day led to a reduction in agitation, with a clinically relevant effect size: on one measure, 40 percent of citalopram-treated participants were judged to be much or very much improved vs 26 percent of those in the placebo group. The researchers did find a worsening of cognition and higher risk of ECG changes that could predispose to an abnormal heart rhythm in the citalopram group, and conclude that citalopram “cannot be generally recommended as an alternative treatment option at that dose.”

“An assessment of individual patient circumstances, including symptom severity, value of improvement, cognitive function and change, cardiac conduction, vulnerability to adverse effects, and effectiveness of behavioral interventions can help guide appropriate medication use in patients with marked agitation or aggression,” the authors add.


Anton P. Porsteinsson MD, Lea T. Drye PhD, Bruce G. Pollock MD, PhD, D. P. Devanand MD, Constantine Frangakis PhD, Zahinoor Ismail MD, Christopher Marano MD, Curtis L. Meinert PhD, Jacobo E. Mintzer MD, MBA, Cynthia A. Munro PhD, Gregory Pelton MD, Peter (2014). Effect of Citalopram on Agitation in Alzheimer Disease: The CitAD Randomized Clinical Trial JAMA DOI: 10.1001/jama.2014.93

Editor’s Note:

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Treating Dementia and Agitation

Until more informative criteria are available for choosing a particular drug treatment for agitation, clinicians should continue to emphasize nonpharmacological strategies and opt for medications with caution, writes Gary W. Small, M.D., of the University of California, Los Angeles, in an accompanying editorial.

“In addition to educating caregivers and family members about the potential risks and benefits of particular medications, physicians should carefully document their treatment plans and aim for short-term treatment to minimize the possible added risks of long-term use. As demonstrated by the results of this study of citalopram, when behavioral interventions fail to improve agitation, multiple factors need consideration for selecting the best medication for an individual patient, including cardiac safety issues and evidence of efficacy from randomized controlled trials. Until more definitive treatments are available, the careful selection and monitoring of pharmacologic agents may help optimize the level of functioning and quality of life for some patients with dementia.”


Gary W. Small MD (2014). Treating Dementia and Agitation JAMA DOI: 10.1001/jama.2014.94

Editor’s Note:

Please see the article for additional information, including financial disclosures, funding and support, etc.

Media Advisory:

To contact Anton P. Porsteinsson, M.D., call Julie Philipp at 585-275-1309 or email To contact editorial author Gary W. Small, M.D., call Rachel Champeau at 310-794-2270 or email

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