SSRI Improves Behavior Symptoms In Demented Elderly Patients

Elderly demented patients who experience behavioral disturbances may be effectively treated with the selective serotonin reuptake inhibitor citalopram, according to new research. If the results hold up in future research, the highly selective SSRI, well known for its benign interaction and side-effect profiles, may offer patients an equally effective, but far safer, alternative to conventional treatment with antipsychotic medications.

Psychotic and behavioral disturbances such as hallucinations, delusions, restlessness, disruptive vocalizations, and aggression are often among the most distressing aspects of dementia, including Alzheimer’s disease, and are frequently cited as the reason for families to admit relatives to long-term-care facilities, according to Bruce Pollock, M.D., Ph.D., the study’s principal investigator and his coauthor, Jules Rosen, M.D.

Pollock’s team of researchers randomly assigned more than 80 hospitalized patients with at least one moderate-to-severe target symptom of behavioral disturbance to citalopram; the conventional neuroleptic, perphenazine; or placebo, for up to 17 days while hospitalized.

Only patients receiving citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors.

The study, funded through grants from the National Institute of Mental Health, was reported in the March issue of the American Journal of Psychiatry.

Pollock, director of the Geriatric Psychopharmacology Program at the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic, became interested in using citalopram for behavioral disturbances in the early 1990s when Scandinavian researchers published reports using the drug—which at the time was not yet approved in the U.S.—to attempt to alleviate cognitive decline in patients with Alzheimer’s disease.

“They had done some neurochemical work on postmortem brains and felt there was definitely evidence of deficit in serotonin in Alzheimer's disease patients,” Pollock told Psychiatric News.

Although the Scandinavian researchers found no improvement in cognitive function with citalopram, they noted that family members of patients in the study receiving the drug requested that their relative remain on the medication after the study ended. When asked why, the families consistently remarked that the patients’ behavior seemed to have improved on the drug.

Pollock obtained approval from the FDA to use citalopram as an investigational new drug. He believed there was some evidence at the time to link serotonin dysfunction to aggression and impulsive disorders.

“Where the billions of dollars have been invested in the pharmaceutical industry has been in trying to improve treatment of the cognitive aspects of Alzheimer’s disease,” Pollock said. “No one in industry would even look at this proposal, so it was vitally important that NIMH funded this study.”

Rosen, a professor of psychiatry and director of the geriatric psychiatry fellowship at the University of Pittsburgh, saw the great need from the clinical point of view. He had seen countless numbers of patients on haloperidol, perphenazine, or another sedating medication and knew that it was not the best medicine.

“We all know that the data supporting the use of conventional neuroleptics [like haloperidol or perphenazine] to treat behavioral disturbances are quite marginal at best,” he told Psychiatric News. “And I was looking at these people and was thinking, What am I really treating? And I came to realize that agitation is really a constellation of other different symptoms. You have people who are really dysphoric and truly miserable, you have people who are very anxious, you have people who are obsessive or impulsive. So I started trying to understand these patients less by throwing them into the grab-bag of agitation, and more as to what we really needed to be treating in these individuals. And SSRIs kept jumping out at me.”

The team is now working on a second NIMH-funded study, comparing citalopram with risperidone.

“This study will take the scientific exploration of the issue to a new level,” Rosen commented. “The idea is not simply to get people well in the hospital and then discharge them but to extend that and see the interaction between the drug’s effects and the environment. By following people back into the nursing home for up to three months, we are really trying to determine if there is a differential [between the two drugs].”

Both Rosen and Pollock believe that the SSRI and the atypical antipsychotic risperidone will be effective in the new study. What they would like to see is whether one or the other helps patients adjust better to the nursing-home environment. Both also stressed that they did not want to overstate the first study’s results, noting that it involved a relatively small sample, over a short period.

“What we did show,” Pollock concluded, “was a positive effect of citalopram that, contrary to what we would have expected, helped to alleviate not just the agitation, but the psychotic symptoms in Alzheimer’s disease, a lot of which were visual hallucinations.”

The study, “Comparison of Citalopram, Perphenazine, and Placebo for the Acute Treatment of Psychosis and Behavioral Disturbances in Hospitalized, Demented Patients,” is posted on the Web at http://ajp.psychiatryonline.org/cgi/content/full/159/3/460. ▪

Am J Psychiatry 2002 159 460