The use of the medication citalopram was associated with a reduction in agitation in patients with Alzheimers 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.
Agitation, which is common in patients with Alzheimer’s disease, is persistent, difficult to treat, costly and associated with severe adverse consequences for patients and caregivers, researchers noted in background information for the study, which was published in the Feb. 19 issue of the Journal of the American Medical Association.
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. 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, MD, of the University of Rochester (N.Y.) School of Medicine and Dentistry, and colleagues from 11 other sites randomized 186 patients with probable Alzheimers disease and clinically significant agitation, and without major depression, to receive citalopram or placebo for nine weeks at eight medical centers in the U.S. and Canada. Both groups received psychological counseling and assistance.
Treatment with citalopram at 30 mg per day led to a reduction in agitation, with a clinically relevant effect size: On one measure, 40% of citalopram-treated participants were judged to be much or very much improved, compared with 26% 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 concluded 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 added.
In an accompanying editorial, Gary W. Small, MD, of the University of California, Los Angeles, wrote that 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.
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, Small wrote.
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.