The latest Phase III clinical trial of donepezil (Aricept) as a possible treatment for vascular dementia showed some effect on memory and thinking tests but no benefit in terms of the doctor’s or caregiver’s overall impression of whether a person is doing better, according to an announcement of preliminary results by Eisai Co., Ltd., the drug’s manufacturer.

Scientists also noted 11 deaths in trial participants taking donepezil compared with none in those taking a placebo.

Eisai says that in two earlier large trials of donepezil as a treatment for vascular dementia, deaths among participants taking the drug did not differ significantly from the placebo group. The company also says there is no significant difference when deaths in all three trials are analyzed together.

“The excess deaths in this trial are a very surprising result and outside our typical experience with donepezil over the 10 years it’s been approved to treat mild to moderate Alzheimer’s,” says Sam Gandy, M.D., Ph.D., chair of the Alzheimer’s Association Medical and Scientific Advisory Council and director of the Farber Institute for Neurosciences at Philadelphia’s Thomas Jefferson University. “But this is why we do clinical trials. Until we resolve any questions about donepezil’s safety or effectiveness in treating other conditions, it will be important to limit its use to the approved purpose.”

This trial enrolled 974 older adults with vascular dementia, a disorder in which disruptions to the brain’s blood supply cause problems with thinking, memory, reasoning and judgment. No participants had ever been diagnosed with Alzheimer’s, but the majority had a history of stroke and/or heart disease and most were taking other medications, usually to treat cardiovascular conditions or risk factors.

Both the excess deaths in the donepezil group and the complete absence of deaths in the placebo group were unusual findings. It’s possible the unexpected difference occurred simply due to chance, but statistical analysis suggests that’s unlikely.

At this time, results of the vascular dementia trial do not change our understanding of the risk/benefit profile for donepezil in treating Alzheimer's disease.