Drugs to Ease Agitation of Alzheimer’s May Pose Risks

October 26, 2006

October 26, 2005

Certain medications commonly prescribed to ease agitation, aggression, and other behavioral problems in people with Alzheimer’s disease may slightly increase the risk of dying, researchers report. People who are taking these drugs should not stop taking them on their own, however. The risk of death was slight, and these drugs can be quite useful for their soothing and calming effects.

People with Alzheimer’s and their families should discuss the use of such drugs with their doctors and weigh the risks and benefits carefully. For example, the authors of the study suggest that if an antipsychotic is not having a beneficial effect, then it should be stopped. But when such a drug does benefit the patient (for example, if it reduces or eliminates agitation), taking the patient off the drug might pose a greater danger than continuing with the drug.

The drugs in the current analysis that posed potential risks, known as “antipsychotics” because they fight symptoms of psychosis, include Risperidone (sold under the brand name Risperdal) Olanzapine (Zyprexa ); Quetiapine (Seroquel); and Aripiprazole (Abilify).

These drugs are commonly given to treat aggression, delusions, hallucinations, agitation, and other behavioral disturbances in people with Alzheimer’s and other conditions. A majority of elderly men and women who suffer from Alzheimer’s and other forms of dementia develop behavior problems, particularly as the disease progresses and becomes more severe.

Earlier this year, the Food and Drug Administration issued a warning cautioning about the potentially deadly risk of such drugs. [See the article, “Some Alzheimer’s Drugs Carry Serious Risks“]. Doctors were told they can still prescribe the medications, but that they and consumers should be alerted to the slight increase in mortality the drugs pose.

Doctors refer to these particular medications as “atypical” antipsychotics because they are a newer form of psychosis-fighting medication. In the last ten years, these “atypical” antipsychotics have been given much more often than older psychosis fighters such as haloperidol (Haldol) and thioridazine (Mellaril). These older drugs are generally less effective in treating Alzheimer’s than the atypicals, and they also pose an increased risk of death.

What the Study Found

Doctors at the University of Southern California in Los Angeles arrived at their conclusions after pooling findings from 15 different medical studies involving more than 5,000 seniors with dementia. They found that compared to those taking dummy pills (a placebo), those taking a so-called “atypical” antipsychotic drug were slightly more likely to die because of a stroke or from other causes. The risk was only slightly higher for those taking these drugs but, nevertheless, it was statistically significant. The doctors couldn’t determine if one drug was safer than another.

“These findings emphasize the need to consider certain changes in some clinical practices,” the authors write. “Antipsychotic drugs have been dispensed fairly frequently to patients with dementia and used for long periods. The established risks for cerebrovascular adverse events together with the present observations suggest that antipsychotic drugs should be used with care in these patients.”

The authors caution that their results need further confirmation, but they also note that if someone with Alzheimer’s who suffers from agitation or other behavioral problems is given one of these drugs, they should begin to show improvement within one to four weeks. If, after a month or so, they do not appear to be responding to the drug, then it may be prudent for their doctor to stop giving it to them. In the current batch of studies that the authors examined, people took one of the medications in question for 10 to 12 weeks, which was long enough for the increased risk of death to become apparent.

Safer Alternatives?

In an editorial accompanying the study, Peter V. Rabins, M.D., M.P.H., and Constantine G. Lyketsos, M.D., M.H.S., of Johns Hopkins Medical Institutions in Baltimore, point out that these findings do not mean that these drugs should not be used in people with dementia who have symptoms of psychosis and agitation. Rather, they alter the risk-benefit profile, so that these drugs should be used if someone may harm himself or others, if the symptoms cause serious distress, or when alternative treatments have failed. For many people, behavioral therapies and antidepressant drugs offer significant relief from agitation and other behavioral problems.

If an elderly person with dementia develops aggression, agitation, or other behavioral problems, they recommend that doctors follow three steps to minimize risks:

First, they note, behavioral problems may arise because of issues unrelated to Alzheimer’s disease or dementia. Untreated or inadequately treated medical illnesses, misinterpretation of medical symptoms, too high a dose of a medication, environmental triggers, or lack of engaging activities are among the conditions that can contribute to behavior problems. These other potential causes should be assessed and sometimes an adverse condition can be remedied. If such a condition is contributing to the problem of agitation, it should be corrected (if possible) before turning to antipsychotic drugs.

Second, doctors need to weigh the risk-benefit ratio for each individual. For example, someone who is suffering from hallucinations and delusions but who is neither distressed by these symptoms nor distressing to others and who is not placing themselves or others at risk or harm, should not be treated with antipsychotic drugs.

Finally, once an antipsychotic drugs has been prescribed, it is important that heath care professionals carefully assess and monitor the situation. Someone should not necessarily continue on these drugs long term. They advise that because many people with dementia live in assisted living homes, these medical practices should be followed in those locations as well.

The current study appeared in the October 18 issue of the Journal of the American Medical Association.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Lon S. Schneider; Karen S. Dagerman; Philip Insel: “Risk of Death With Atypical Antipsychotic Drug Treatment for Dementia: Meta-analysis of Randomized Placebo-Controlled Trials.” Journal of the American Medical Association, Volume 294, Pages 1934-1943, October 18, 2005

Peter V. Rabins; Constantine G. Lyketsos: Antipsychotic Drugs in Dementia: What Should Be Made of the Risks? (editorial) Journal of the American Medical Association, Volume 294, Pages 1963-1965, October 18, 2005


Alzheimer's Articles