Alzheimer’s: Celexa Reduced Agitation, Has Modest Cognitive, Cardiac Side Effects

Anton P. Porsteinsson M.D. William B. and Sheila Konar Professor of Psychiatry Director, Alzheimer's Disease Care, Research and Education Program (AD-CARE) University of Rochester School of Medicine and Dentistry Rochester, N.Y. 14620MedicalResearch.com Interview with:
Anton P. Porsteinsson M.D.
William B. and Sheila Konar Professor of Psychiatry
Director, Alzheimer’s Disease Care, Research and Education Program (AD-CARE)
University of Rochester School of Medicine and Dentistry
Rochester, N.Y. 14620

MedicalResearch.com: What are the main findings of the study?

Dr. Porsteinsson: Identifying drugs outside the antipsychotic class with targeted anti-agitation effects that provide greater benefit or lower risk among patients with Alzheimer’s disease is a research priority.  Citalopram, a selective serotonin reuptake inhibitor (SSRI), is frequently used in older individualsand has been suggested as an alternative to antipsychotic drugs for agitation and aggression in dementia.  Among 186 patients with probable Alzheimer’s disease and agitation receiving psychosocial intervention, the addition of citalopram compared with placebo robustly and significantly reduced agitation and caregiver distress, but modest cognitive and cardiac adverse effects of citalopram may limit its practical application at the 30 mg/d dose studied in this trial. There are insufficient data on efficacy for agitation at lower doses of citalopram.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Porsteinsson: Three quarters of the way through the study, the Food and Drug Administration (FDA) issued an advisory regarding dose-dependent risk of QT prolongation with citalopram therapy that subsequently came under scrutiny.  We added ECG monitoring and QT interval prolongation was seen in the citalopram group similar to what had been described in the advisory for a younger population and our findings validate the FDA’s action.  Furthermore, an unexpected modest cognitive decline was seen in the citalopram group compared to placebo over 9 weeks with no difference in spontaneously reported somnolence or confusion.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Porsteinsson: Neuropsychiatric symptoms occur in a majority of patients with Alzheimer’s disease.  Agitation is common, persistent, difficult to treat, costly, and associated with severe adverse consequences for patients and caregivers.  Psychological, environmental and pharmacologic therapies have proven inadequate.  Antipsychotics continue to be widely used for agitation, despite serious safety concerns, including increased mortality, and uncertain efficacy.  The takeaway message is that there are very limited options for the treatment of this tremendously distressing and difficult to treat behavioral disruption.  If non-pharmacological intervention is not beneficial, judicious use of citalopram appears to have a role in managing agitation in patients with Alzheimer’s disease but generally the dose should not surpass 20 mg/d.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Porsteinsson: Given potentially concerning side effects of citalopram at 30 mg/d, further investigation is needed to determine whether a smaller dose will be as effective.

Citation:

Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of Citalopram on Agitation in Alzheimer Disease: The CitAD Randomized Clinical Trial. JAMA. 2014;311(7):682-691. doi:10.1001/jama.2014.93.