Antidepressant Helps With AD Agitation

By Sondra Forsyth

The antidepressant drug citalopram, sold under the brand names Celexa and Cipramil and also available as a generic medication, significantly relieved agitation in a group of patients with Alzheimer's disease, according to research led by a Johns Hopkins team and reported in the February 19th issue of the Journal of the American Medical Association. However, side effects including sings of abnormal heart function and a slight increase in cognitive decline. A release from the university notes that the team hopes that in lower doses than those tested, the drug might be safer than antipsychotic drugs that are currently used to treat the condition and that also pose a heart risk.

Along with Johns Hopkins, he study was done by researchers at Columbia University, the Medical University of South Carolina, Stanford University, the University of Pennsylvania, the University of Rochester, the University of Southern California, and the University of Toronto.

Constantine Lyketsos, M.D., M.H.S., and his colleagues recruited 186 patients with Alzheimer's who showed a collection of symptoms including emotional distress, excessive movement, aggression, disruptive irritability, and lack of appropriate inhibition. None of the participants experienced adequate symptom relief with non-medical therapies, and treatment with antipsychotic drugs failed for some of the patients. Though antipsychotics are often used as first-line medications for Alzheimer's-related agitation, they significantly increase the risk of strokes, heart attacks, and death, Lyketsos says.

The release explain that at the start of the study, patients also underwent tests to define the extent of their agitation, memory and other cognitive skills, and their caregivers' stress levels, a factor strongly linked to the well-being of those with Alzheimer's. The patients were then separated into two groups. For the next nine weeks, about half took increasing doses of citalopram that peaked at 30 milligrams per day, and the rest took an identical-looking placebo.

At the end of the study period, the same set of tests was given, along with electrocardiograms. The study drug is linked to adverse effects on heart function, including irregular heartbeat, a harbinger of a heart attack.

Results showed that patients on the drug had significant relief from their agitation symptoms, Lyketsos says. In one measure of agitation, about 40 percent of patients who took citalopram had "considerable relief," compared to 26 percent of patients who took the placebo. The caregivers for the patients who took the actual reported less stress.

However, as noted above, patients on the drug were also more likely to have slightly decreased cognitive function. "It was not huge, but measureable," says Lyketsos, director of the Johns Hopkins Memory and Alzheimer's Treatment Center and director of the Department of Psychiatry at Johns Hopkins Bayview Medical Center. "That introduces a tradeoff."

More concerning, he adds, is that patients on citalopram had longer QTc intervals, a measure of abnormal heart function that increases the risk of heart attacks. However, Lyketsos says, antipsychotic medications increase heart attack risk as well, perhaps even more substantially.

Lyketsos and his colleagues hope to test whether or not a lower dose of citalopram might be just as effective in treating Alzheimer's-related agitation with less risk for problems with cognition and heart function. In the meantime, he says, the drug offers an alternative to antipsychotics.

"If the agitation is not responding to non-medication treatments and your patient's agitation isn't improving, there are no great options," Lyketsos says. "But here's another medication choice that might be safer than other medications and seems to be just as effective."