Doctors Not Surprised By 11 Patient Deaths in Dementia Drug Trial

March 17, 2006 — -- Doctors were not surprised to hear the news that 11 people in a clinical trial died while taking Aricept, a drug currently approved for use for patients with Alzheimer's disease.

What was surprising, they said, was the lack of deaths in the placebo group.

The people were all enrolled in a study investigating whether Aricept, currently approved for use for patients with Alzheimer's disease, also might help people suffering from vascular dementia, a brain disorder that lessens a person's ability to think and perform daily activities. It is caused by damage to the blood vessels bringing oxygen-rich blood to the brain.

In the trial, 648 patients received Aricept for 24 weeks while 326 patients received an inactive medication, or placebo. Overall, 1.7 percent of the patients taking Aricept died.

That may seem unusually high, but several doctors said they were not surprised by the number of deaths in the patients taking Aricept.

Patients with vascular dementia are often older and have other diseases that damage blood vessels, such as diabetes, high blood pressure and heart disease. This means patients with vascular dementia have a higher risk of death than healthy patients of the same age.

"The death rate in this study for the [Aricept] group does not differ greatly from that in previous trials. The unexpected difference is in the placebo group," said Dr. Myron F. Weiner, a psychiatry and neurology professor at the University of Texas Southwestern Medical School in Dallas. "I can't explain why the placebo group did so well."

Drug is Safe, Doctors Attest

Ard is not alone in his assessment -- multiple experts said they could not explain why the patients taking a placebo would have such a low death rate.

They did note, however, that this kind of finding can occur by random chance, representing a statistical fluke, when studies are performed.

"What seems to strange here is the fact that the placebo group had no deaths -- much fewer than expected given the illness level of the subjects participating in the trial," said Dr. George Bartzoki, director of the UCLA Memory Disorders and Alzheimer's Disease Clinic. "It is the placebo group that had unusually few deaths, not that the Aricept group had unusually more deaths."

Aricept, also known as donepezil, has been approved in the U.S. since 1994 for the treatment of mild to moderate Alzheimer's disease, the most common form of dementia. Many Americans have been taking Aricept for Alzheimer's disease since it was approved. It is manufactured by the Japanese drug company Eisai.

While the latest study results may alarm patients currently taking the drug, doctors said it has a proven safe track record.

"I think [Aricept] and drugs like it remain safe and effective treatments for their FDA-approved use in Alzheimer's disease," said Dr. Amanda G. Smith, the assistant director of the Suncoast Alzheimer's and Gerontology Center at the University of South Florida.

Dr. Rachelle Smith Doody agreed.

"With respect to Alzheimer's disease, there is a huge database on safety and no suggestion of an increased risk for death. The new data should not affect the use of Aricept for Alzheimer's disease," said Doody, of the Alzheimer's Disease Center at Baylor College of Medicine in Texas.

But what does this study mean for patients with both forms of dementia?

Talk to Your Doctor First

Doody said that the disparity in deaths among the two groups of patients "was not seen in two previously published studies of Aricept for vascular dementia."

"Patients with mixed Alzheimer's disease and vascular dementia have been safely treated [with Aricept] for years," she said.

While it can be alarming when research seems to show an unusual rate of death in patients taking a medication, but Dr. Amanda Smith said the findings shouldn't be taken out of context.

And, she said, most importantly, "patients should not stop taking their medication without speaking to their doctors first."

Schofer is a chief resident in emergency medicine at Naval Medical Center San Diego. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.