Extended treatment with Alzheimer's drugs may provide modest cognitive benefit, study shows


A new study of patients with moderate-to-severe Alzheimer's disease found that extended treatment with donepezil could improve cognition and function for even severe patients; however, experts caution that the benefits of the drug were modest.

A new study of patients with moderate-to-severe Alzheimer's disease found that extended treatment with donepezil could improve cognition and function for even severe patients; however, experts caution that the benefits of the drug were modest.

The study, done in London and published in the March 8 issue of the New England Journal of Medicine, also found that memantine, another Alzheimer's medication commonly prescribed, improved some cognition and functioning in patients who have moderate-to-severe or severe progression of the disease, but not at clinically significant levels.

Taking both Alzheimer's drugs together-a common practice in the United States-showed no benefit.

The 295 participants in the study had been treated with donepezil for at least 3 months and had moderate-to-severe Alzheimer's disease. They were randomly assigned to 1 of the 4 following groups:

They found that those patients who had been assigned to take donepezil had scores on the SMMSE that were 1.9 points higher (95% CI, 1.3-2.5; P<.0001) on average than those patients taking a placebo. Their scores on the BADLS were also an average of 3.0 points lower (95% CI; 1.8-4.3; P<.0001), showing less impairment. The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.

The difference in scores on the 2 exams for patients taking memantine were less pronounced and failed to meet the minimum requirements necessary to indicate a clinically important difference.

Jack Rosenberg, PharmD, PhD, a professor emeritus of pharmacy practice and pharmacology at Long Island University, said that while the study did show cognitive improvement for patients who were taking donepezil, it also showed that these benefits were more significant for patients in the moderate stages of the disease. The effect was minimized for those in more severe stages of Alzheimer's.

Neither drug is a panacea, he said, and won't stop the decline in Alzheimer's patients and may only slow the progression of the fatal brain disease.

But even with modest results, Dr Rosenberg, who operates a consulting pharmacy practice at long-term care facilities and adult day care centers, said that it could provide an important benefit for those Alzheimer's patients who are still living at home. Even a modest benefit in daily living and cognitive abilities may help these patients stay out of long-term care facilities longer.

"I think it is some ammunition to continue [donepezil], at least under the terms of the study, for a 1-year period," he said.

Patients and their families will also need to weigh the benefits of any slowing decline from the medication with the side effects often associated with donepezil, he said. Donepezil can cause weight loss, agitation, and nausea in patients and many often discontinue use of the drug either due to the side effects or a perceived lack of benefit.


Michael Swanoski, PharmD, CGP, FASCP, assistant professor in the department of pharmacy practice and pharmaceutical sciences at the University of Minnesota, said this latest study also might have important implications for the medical community.

Clinicians may start to think differently about putting patients on a combined regimen of memantine and donepezil after the study found there was no benefit to using the 2 medications together, according to Dr Swanoksi.

"It sort of changes the way I think of things," he said.

Dr Swanoski said the study seems to suggest administering donepezil alone to patients since it had the largest impact on both cognitive and functional abilities, but memantine may be an option on its own for those patients who don't tolerate donepezil well.

Drs Swanoski and Rosenberg both agreed that the findings from the study also could be helpful when counseling families and trying to decide when to stop the use of these medications.

This is often a challenge for both the families and clinicians because it isn't always obvious whether the medications are having an influence, but the DOMINO study provides some clarity about the impact the drugs have on patients' cognition and daily functioning.

Based on the study's findings, the benefits of the donepezil seem to be more significant in the earlier stages of the disease and make less of an impact as patients enter the severe phase of Alzheimer's.

Even with the DOMINO study results, it is difficult to put a time limit on how long donepezil or memantine may be effective because the drugs often affect each patient differently; however, Dr Swanoski said it may be time to have the discussion once patients enter the severe stage of Alzheimer's.

"I think you have to base it on individual patient response," he said.

He added that when patients stop taking the medications it is best to taper them off slowly to determine whether the medication was still beneficial.

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