New Study Further Links Alzheimer's Drugs to Side Effects

A study published in the May 11, 2009, issue of Archives of Internal Medicine provides more evidence that syncope (fainting) can be a serious side effect of the Alzheimer’s disease drugs donepezil (ARICEPT), rivastigmine (EXELON) and galantamine (REMINYL).

Syncope (commonly known as fainting) is the medical term for a sudden loss of consciousness, usually from a standing or seated position. Often, syncope leads to falling, resulting in injuries.

In the Archives study, almost 20,000 patients with dementia who were taking donepezil, rivastigmine or galantamine were compared with over 60,000 patients who also had dementia but who were not taking these drugs. Researchers then looked at the rate of hospitalization for syncope.

They found that that rate of syncope was 76 percent higher in patients taking these drugs compared to patients not taking them, even after controlling for other factors than can contribute to syncope (such as age, heart disease and the use of other drugs that can affect heart rate or rhythm). In addition, hospitalizations for slow heart rhythms, pacemaker insertions and hip fractures — all of which can be related to syncope — increased in patients using these Alzheimer’s drugs.

The higher rate of requiring a pacemaker is particularly concerning, because this invasive procedure is associated with its own risks, and could be averted in some cases simply by stopping the offending drug.

Syncope related to these drugs does not always occur immediately after starting the drug. It can be exacerbated by interactions with other drugs or other factors that contribute to syncope, such as dehydration or low blood pressure.

One limitation of this study was its design, which was observational, not experimental. That means that the results may have been influenced by other unseen factors. However, because of the strength of the findings and their strong biologic plausibility, it is very likely that syncope, slow heart rhythms and hip fractures can be caused by these Alzheimer’s drugs.

Previous Worst Pills, Best Pills News articles have discussed these drugs (see Worst Pills, Best Pills News October 2005, February 2005 and July 2004). They belong to the family of drugs known as cholinesterase inhibitors, which inhibit the enzyme that breaks down acetylcholine, a brain transmitter. A deficiency of acetylcholine is thought to play a role in Alzheimer’s disease and other forms of dementia.

Several reviews of clinical studies have shown that the effectiveness of these drugs in improving cognitive symptoms is minimal, if it exists at all. One review published in the British Medical Journal in 2005 stated that "the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer’s disease is questionable."

In addition, these drugs have several well-known side effects, including nausea, diarrhea, muscle cramps and urinary incontinence in addition to the aforementioned abnormally slow heart rhythms. The combination of questionable effectiveness and many side effects, some of which can be life-threatening, has led us to list donepezil, rivastigmine and galantamine as Do Not Use since they were approved, in 1996, 2000 and 2001, respectively.

What You Can Do

Do Not Use donepezil, rivastigmine or galantamine because of their questionable effectiveness and known side effects. Adding syncope, slow heart rhythms and hip fractures to the list of side effects caused by these drugs only strengthens our previous recommendation.