The practical application of the medication citalopram, associated with a reduction in agitation in patients with Alzheimer disease, should be limited to a dosage of 30 mg per day, as higher dosage might result in mild cognitive and cardiac adverse effects in patients, suggests a study in the February 19 issue of JAMA.
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. Available pre-embargo to the media at media.jamanetwork.com
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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.
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.