WEDNESDAY, Oct. 3, 2007 (HealthDay News) -- Aricept, a drug commonly used to treat the cognitive symptoms of Alzheimer's disease, is no better than a placebo when it comes to treating the agitation associated with the illness, a new study finds.
When combined with other research, the trial suggests that doctors and patients shouldn't rule out using the medication, but they shouldn't count on it either, experts said.
"This is part of a greater dialogue about how you deal with these behavioral symptoms of Alzheimer's and I think the findings are relatively consistent with what's been seen before," said William Thies, vice president of medical and scientific relations at the Alzheimer's Association.
Previous trials have shown some variation in the effectiveness of cholinesterase inhibitors -- the class of medicines to which Aricept (donepezil) belongs -- in easing agitation. However, any positive effect from the drug has typically been small.
Although memory loss and cognitive dysfunction are hallmarks of Alzheimer's disease, behavioral disturbances such as agitation can cloud other changes, experts say. The group of symptoms known as "agitation" can lead patients to pace, wander, shout and become aggressive.
"These kinds of symptoms are very difficult to deal with and, both from a care and a medical perspective, they are the most likely causes of people moving into some sort of care facility as opposed to being cared for at home," Thies noted. "Memory issues often can be dealt with but when people get aggressive and agitated, that is frequently going to go beyond what a single caregiver can manage."
"Agitation is difficult to address in the first place," added Dr. Gary J. Kennedy, director of geriatric psychiatry at Montefiore Medical Center in New York City.
Antipsychotics and tranquilizers are commonly used to treat these behavioral disturbances but the effect -- if any -- is usually small and the side effects can be severe.
Cholinesterase inhibitors like Aricept have been shown to improve cognitive outcomes but the benefits in terms of behavioral disturbances have been unclear.
This British trial was originally designed to compare the efficacy of Risperdal (risperidone), a tranquilizer, against Aricept and a placebo. During the course of the trial, however, British regulatory authorities issued guidance saying that drugs such as Risperdal should not be given to Alzheimer's patients because of an increased incidence of stroke.
The trial therefore continued as a comparison of Aricept against placebo. Researchers randomly assigned 272 patients with Alzheimer's who also had agitation to receive 10 milligrams of donepezil per day or a placebo for 12 weeks. The patients had tried, but not responded to, a brief psychosocial treatment before being given medication. Most of the participants resided in nursing homes and had severe dementia with difficult-to-manage behaviors.
At the end of the study period, there was no significant difference in agitation between patients in the Aricept group and those in the placebo group, the research team report in the Oct. 4 issue of the New England Journal of Medicine.
There was a modest improvement in cognitive function among participants taking Aricept, however.
"It is becoming increasingly clear that tranquilisers are not an adequate treatment for managing behavioural symptoms in Alzheimer's patients and their use is associated with serious potential side effects," lead researcher Dr. Robert J. Howard, a professor of old age psychiatry at the Institute of Psychiatry, King's College London, said in a statement. "Sadly, but importantly, our results show that while donepezil may improve memory and attention in some patients, it is not effective in the management of these distressing behaviours."
According to Kennedy, there may be some question of whether this study can be extrapolated to practice in the United States. "In the U.K., few people are treated with cholinesterase inhibitors," he said. In the U.S., many people are on Aricept and related drugs to deal with cognitive problems and this may have a delaying effect on agitation. Prevention is a completely separate issue from treatment, the subject of this study.
"Just because donepezil, once they're agitated, doesn't seem to have much impact doesn't mean we don't have other agents to use," Kennedy said. "The danger is people will misread this study saying donepezil has no benefit for agitation when, in reality, the family of cholinesterase inhibitors may delay the emergence of agitation. It's an important study but it lends itself to misinterpretation."
The question, now and before, is how to best manage these patients.
"One of the things we can be pretty much guaranteed of is whatever effect there is is going to be small and highly individual," Thies said. "Every one of these people is different but having an orderly approach to them would be useful, looking at non-pharmacological interventions first. If you are going to treat for cognitive symptoms, certainly using a cholinesterase inhibitor is one of the first things you're going to try. If you benefit, that's good and an individual success but don't expect it to happen all the time."
There is some hope in the form of a recent study that found that Celexa (citalopram), an antidepressant, may help control agitation and psychotic symptoms associated with Alzheimer's. That study appeared in the Sept. 10 online issue of the American Journal of Geriatric Psychiatry.
For more on Alzheimer's disease, visit the Alzheimer's Association.