Researchers reported that three drugs commonly used to calm agitation and aggression in Alzheimer’s patients are not more effective than placebos and put patients at risk for serious side effects, including Parkinson’s disease-like symptoms. This is the third report in the last year to conclude that atypical antipsychotics are not as effective or as safe as originally thought.

The three drugs tested in the study - Zyprexa, marketed by Eli Lilly; Seroquel, marketed by AstraZeneca; and Risperdal, marketed by Janssen Pharmaceutical - are known as atypical antipsychotics and are primarily used to treat schizophrenia. They are often prescribed for elderly patients in long-term care facilities.

Overall, the report found the adverse effects of the three drugs outweighed the benefits, with up to a quarter of the patients in the study dropping out because of the effects.

Some of the side effects observed include:

• Parkinson’s disease-like symptoms, including tremors (12 percent)
• Sedation (15-24 percent of the patients)
• Confusion (6 percent of the patients)

Risperdal, Zyprexa and Seroquel were not approved by the Food and Drug Administration (FDA) for use in Alzheimer’s patients. About 4.5 million Americans suffer from the progressive dementia of Alzheimer’s disease, with most exhibiting agitation or delusions at some point. Almost one-third of the 2.5 million Medicare beneficiaries in nursing homes in the US have taken the medications, accounting for an estimated $2 billion in the annual sales of the drugs.

“The question is whether these drugs have a place in the treatment of Alzheimer’s patients at all,” Dr. Jason Karlawish, an associate professor of medicine at the University of Pennsylvania, said. “I think the answer is yes, but only for a subgroup of patients who can tolerate them, and in facilities that have the expertise to manage the side effects.”

The drugs are required by the FDA to have a black-box warning on the prescription drug insert that states, “elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo.”

Researchers in the study followed 421 Alzheimer’s patients who suffer from agitation, delusions or hallucinations. After 12 weeks, there were no signs of significant improvement. About 80 percent stopped taking the drugs and the placebos alike before the end of the study, and those on the drugs were found more likely to quit because of side effects.

“What this study shows is that these drugs are clearly not the answer; they may be helpful for a minority of patients but we need to come up with better medications,” Dr. Thomas R. Insel, director of the National Institute of Mental Health, which financed the study, said.

Sources: Benedict Carey, “Alzheimer’s drugs offer no help, study finds,” New York Times, October 12, 2006; Neil Osterweil, “Atypical Antipsychotics Get Poor Grade for Alzheimer’s Psychoses,” MedPageToday, October 11, 2006.