Alzheimer's Disease Medications

Drugs known as cholinesterase inhibitors were the first medications approved by the FDA for the treatment of Alzheimer's disease. These drugs work by slowing the breakdown of acetylcholine, a chemical that is linked to the formation of new memories. These drugs may ease some of the symptoms associated with Alzheimer's, but they do not halt progression of the disease. Cholinesterase inhibitors seem to improve symptoms for about six to 12 months in one third to one half of the people who take them.

Tacrine (Cognex), the first FDA-approved cholinesterase inhibitor, works in only about 20 to 40% of people with Alzheimer's disease and causes liver damage in some individuals. It is rarely used now that a second generation of cholinesterase inhibitors is available.

Second-generation cholinesterase inhibitors produce fewer and less severe side effects. The first one approved by the FDA, donepezil (Aricept), is now approved to treat all stages of Alzheimer's disease.

Clinical trials have shown significant improvements in cognitive and overall functioning in people receiving Aricept (compared with those receiving a placebo), with fewer adverse effects than with Cognex. In one 24-week study, at least 80% of the Aricept patients suffered no cognitive decline, compared with 57% of patients taking a placebo, a difference of 23%.

Improvement was greater with higher dosages of the drug: 54% of the patients taking 10 mg of Aricept improved slightly in one cognitive test, compared with 38% of those taking 5 mg and 27% of those taking the placebo. In another study, patients taking 10 mg of Aricept for one year were half as likely to experience disease progression as those who received a placebo.

In 2009, generic donepezil was approved to treat Alzheimer's as an orally disintegrating tablet that may be easier for patients who have trouble swallowing to take.

The second of these drugs to be approved was rivastigmine (Exelon), which is for mild to moderate Alzheimer's. In four placebo- controlled clinical trials, involving a total of 3,900 people, those taking Exelon had significantly better scores on standard tests of cognitive function than people taking a placebo.

One of these trials, which included 725 people with Alzheimer's disease, found that 24% of the people in the Exelon group showed significant improvements in cognitive function over a 26-week period compared with 16% of those taking a placebo, a difference of 8%.

The newest cholinesterase inhibitor to be approved is galantamine (Razadyne), which is approved to treat mild to moderate Alzheimer's. Its approval was based on data from four placebo-controlled clinical trials involving over 2,650 people. Patients taking Razadyne scored better on measures of cognitive performance and daily functioning than people taking a placebo.

The most common adverse effects of cholinesterase inhibitors are nausea, vomiting, loss of appetite, diarrhea, and weight loss. A recent Canadian study also found that people taking cholinesterase inhibitors for dementia have a significantly higher risk of falls and bradycardia (slow heartbeat); these side effects should be considered before taking a cholinesterase inhibitor.

Publication Review By: Peter V. Rabins, M.D., M.P.H.

Published: 11 Mar 2011

Last Modified: 23 Jun 2011