Aricept Proves Ineffective for the Agitation of Alzheimer’s

October 22, 2007

Aricept, a drug commonly prescribed to treat cognitive decline in mild to moderate Alzheimer’s, proved no more effective than a placebo for easing agitation, restlessness, and other behavioral symptoms of the disease. The results are disappointing, since behavioral complaints are so common in people with Alzheimer’s, and treating them is difficult.

Many people with Alzheimer’s suffer from agitation, a distressing complaint for patients and caretakers alike. Symptoms include anxiety, irritability, and restlessness, often leading to behaviors such as wandering, pacing, shouting, or aggressive behaviors. Additional mood and behavioral complaints, including depression, delusions, hallucinations, and repetitive vocalizations, are also common. Such behavioral complaints are a frequent reason why patients are moved to a nursing home. An estimated 80 percent of Alzheimer’s sufferers living in long-term care facilities exhibit behavioral problems.

The Food and Drug Administration has not currently approved any medications specifically for the treatment of behavioral problems in people with Alzheimer’s. However, doctors commonly prescribe antidepressants (such as Zoloft or Celexa) to Alzheimer’s patients.  These drugs are sometimes successful at relieving agitation.  Doctors may also prescribe anti-psychotics (such as risperidone or olanzapine).  These drugs may or may not help.

Aricept and related drugs, such as Exelon and Razadyne, are commonly prescribed to reduce the symptoms of cognitive decline that occurs with Alzheimer’s. These drugs, called cholinesterase inhibitors, alter levels of brain chemicals critical for memory and thinking. However, their benefits are modest at best, and they do  not stem the ultimate downward progression of disease.

Some earlier research suggested that these drugs may help ease restlessness and other disruptive behaviors in people with Alzheimer’s. The current study, known as the CALM-AD trial, for Trial of a Cholinesterase Inhibitor and Atypical Neuroleptic in the Management of Agitation in Alzheimer’s Disease, sought to study the effects of Aricept on the behavioral symptoms of Alzheimer’s.

In the study, British researchers enrolled 272 men and women with Alzheimer’s who suffered from agitation and restlessness. Their symptoms were fairly severe and persisted despite receiving four weeks of music therapy, social interactions, and other therapies aimed at easing agitation. Half of the group received a 10-milligram daily dose of Aricept, also known as donepezil. The other half received a look-alike placebo pill.

After 12 weeks, the study participants were assessed for signs of agitation and other behavioral complaints. Although Aricept produced modest improvements in cognitive function, there was so significant differences in behavioral symptoms in the group receiving Aricept compared to those who got the placebo.

In an editorial accompanying the study, Dr. Kristin Yaffe of the University of California, San Francisco, notes that drugs such as Aricept are still often appropriate for patients with mild to moderate Alzheimer’s, even though they may also exhibit agitation and other behavioral complaints. She notes that management of behavioral symptoms should include a careful medical assessment to rule out treatable conditions such as pain or delirium that may be contributing to the agitation. Excessive noise and other environmental factors that can make people with Alzheimer’s restless should also be eliminated, she notes.

In addition, music therapy and aromatherapy, which employs pleasant scents and fragrances, may also be worth a try for easing the agitation of Alzheimer’s. Counseling and education of Alzheimer’s caregivers is also important, Dr. Yaffe notes.  Although this study did not show a benefit for Aricept in stemming agitation, it should be noted that the researchers focused mainly on patients suffering from severe agitation.  The possibility that Aricept and other cholinesterase inhibitors might reduce some forms of agitation in Alzheimer’s or agitation occurring at different stages of the disease has not been ruled out.

To learn more about effective steps for the care and management of Alzheimer’s disease, visit www.ALZinfo.org, The Alzheimer’s Information Site.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Robert J. Howard, M.R.C.Psych., Edmund Jusczak, B.Vs., Clive G. Ballard, et al:

“Donepezil for the Treatment of Agitation in Alzheimer’s Disease,” The New England Journal of Medicine, October 4, 2007, pages 1382-1392.

Kristine Yaffe, M.D.: “Treatment of Neuropsychiatric Symptoms in Patients with Dementia,” Editorial, The New England Journal of Medicine, October 4, 2007, pages 1441-1442.


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