DIMENSIONS Winter 1997

SECOND FDA-APPROVED DRUG NOW AVAILABLE FOR TREATING AD

Until now Cognex has been the only drug available for treating the cognitive deficits of Alzheimer's disease. Aricept, a new drug that works the same way, except with fewer side effects, provides another option and is likely to benefit more people with AD.

Clinical trials led to Aricept's approval by the Food and Drug Administration in November 1996. The studies showed that the new drug stabilized or improved cognitive symptoms in about 80 percent of Alzheimer's patients. Aricept (trade name for donepezil) became available by prescription in late January.

Like Cognex (trade name for tacrine), Aricept is targeted at the decline in the ability to think and reason that is part of Alzheimer's, explains Dr. Soo Borson, a psychiatrist who treats patients with AD at UWMC Geriatric and Family Services Clinic. Both drugs act by the same biochemical mechanism. They block the breakdown of a chemical called acetylcholine, which enables nerve cells to communicate with each other. People with AD have a shortage of acetylcholine, resulting in reduced cholinergic activity in the brain. Memory loss and other Alzheimer's symptoms are related to this reduction in cholinergic activity.

Although the two drugs have similarities, there are a couple of important differences. "One of the critical limitations in the use of Cognex has been the occurrence of liver toxicity, which has been widely recognized as reversible, but impedes treatment," says Borson, associate professor of psychiatry and behavioral sciences. To avoid liver damage, regular blood monitoring is required. With Aricept, there is no liver toxicity so no blood monitoring is necessary.

A second difference is that Aricept is much longer acting than Cognex.Aricept requires only one dose a day instead of four. "The single dose a day makes it possible to offer treatment to patients who may still be living alone or with minimal supervision. They would only need one reminder to take their pill," says Borson. "The four reminders a day needed for Cognex made it almost impossible to use except for patients who were under continuous supervision."

Neither Aricept nor Cognex cure AD, but by increasing cholinergic activity they can improve cognitive function somewhat. An Alzheimer's patient who is being treated with the drug is still likely to be forgetful, but can show increased levels of overall alertness and engagement in everyday life.

"The benefits of Aricept will vary from patient to patient and right now, we have no way of predicting who will benefit the most," notes Borson. "But we do think that the effects of Aricept on cognitive symptoms will be similar to those of Cognex. In short term trials, substantial benefit is realized in 25 to 30 percent, significant benefit in probably more than 50 percent." Because Aricept is better drug is tolerated, fewer people will be forced to discontinue the medication because of its side effects. Aricept could be tried with nearly everyone with mild to moderate AD, according to Borson. Although if a person is already responding well to Cognex, there may be no reason to switch.

"Side effects of Aricept are primarily related to the fact that acetylcholine breakdown is inhibited. That can result in symptoms of increased cholinergic activity in places where you don't want it. You want it in the brain, but you don't want it in the muscles or in the gastrointestinal tract," says Borson.

The gastrointestinal effects, which are also common with Cognex, include nausea, diarrhea and loss of appetite. Acetylcholine is the chemical responsible for sending messages from the nerves to the muscles. Because Aricept increases the amount of acetylcholine in the body, a person taking it might experience muscle tension, which could cause aching or stiffness. "These are not usually major problems," says Borson. Other possible side effects include increased production of stomach acid, difficult urination, particularly in men, and symptomatic worsening of asthma and other lung conditions.

Insomnia can arise due to the way Aricept works in the brain. "The cholinergic system in the brain is involved in wakefulness, alertness and general mental stimulation as well as regulation of other brain systems," explains Borson. "An Alzheimer's patient who is alert might develop insomnia with that degree of stimulation. Another Alzheimer's patient who is apathetic and withdrawn might benefit from the alerting effect and become more involved in everyday activities."


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