FDA Highlights: Citalopram shows efficacy for Alzheimer’s agitation

by Bruce Sylvester: The antidepressant citalopram (Celexa/Cipramil, and generic) significantly reduces agitation among patients with Alzheimer’s disease, researchers reported in the Feb. 19, 2014 issue of JAMA/Journal of the American Medical Association.

Constantine Lyketsos, M.D., M.H.S., director of the Johns Hopkins Memory and Alzheimer’s Treatment Center and director of the Department of Psychiatry at Johns Hopkins Bayview Medical Center in Baltimore, Maryland, and colleagues recruited 186 patients with Alzheimer’s who manifested emotional distress, excessive movement, aggression, disruptive irritability and disinhibition.

The subjects had achieved inadequate symptom relief with non-medical therapies, and some had experienced failed treatment with antipsychotic drugs.

As background, Dr. Lyketsos noted that while antipsychotics are often used first-line as treatment for Alzheimer’s-related agitation, they can significantly increase the risk of strokes, heart attacks and death.

At baseline the subjects were tested to determine the extent of their agitation, memory and other cognitive skills, and their caregivers’ stress levels.

The researchers divided the subjects into two cohorts. For nine weeks, about half took increasing doses of citalopram, peaking at 30 milligrams per day. The rest took a placebo.

The baseline tests were repeated at endpoint. They also received an electrocardiogram, since citalopram has been linked to adverse effects on heart function.

The subjects treated with citalopram achieved significant relief from their agitation symptoms, and 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 of the actively treated patients also reported less stress.

But the actively treated subjects were also more likely to have slightly decreased cognitive function. “It was not huge, but measureable,” said Lyketsos, “That introduces a tradeoff.”

Of greater concern, Lyketsos added, was the finding that subjects on citalopram had longer QTc intervals, a measure of abnormal heart function that increases the risk of heart attacks. But, he noted, antipsychotic medications used to treat agitation also increase heart attack risk.

The investigators concluded that they hope to test lower dose of citalopram, to see if  it might be just as effective in treating Alzheimer’s-related agitation with less risk for cognition and heart function.

“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,” he  added.