Aricept, Exelon, and Reminyl are in a class of drugs called cholinesterase inhibitors and are typically prescribed for Alzheimer's disease patients and patients with related dementias, said Science Daily, explaining that the drugs increase the brain chemical thought to aid in memory. The drugs also seem to decrease heart rates and prompt fainting, said Science Daily, noting that the enormity of the issue was not previously understood.

"This is very troubling, because the drugs are marketed as helping to preserve memory and improve function. But for a subset of people, the effect appears to be the exact opposite," Dr. Gill said, quoted Science Daily.

Dr. Gill and his team found, based on province-wide data, that patients taking cholinesterase inhibitors experienced the following over those patients not on these drugs: Hospitalizations for fainting, almost twice as often; lowered heart rates occurred 69 percent more often; increased chance of being permanently implanted for pacemakers, about 49 percent more often; and increased risk of hip fractures, 18 percent more often, said Science Daily. Sadly, said Dr. Gill, cholinesterase inhibitors are one of the few effective dementia treatments currently available, reported Science Daily.

Slowed heart rate from cholinesterase inhibitors could cause someone to faint and “suffer fall-related injuries such as a broken hip,” said Science Daily, which could be dangerous, even deadly for the elderly. Unfortunately, many doctors do not know about the link between these dementia drugs and the dangerous side effects, noted Science Daily. A serious problem because, for instance, patients on dementia drugs who faint could be implanted with a pace maker, which would be an unnecessary and dangerous procedure, especially in the frail and elderly, Science Daily pointed out.

The findings are published in the journal, Archives of Internal Medicine and involved scientists from the Institute for Clinical Evaluative Sciences, the University of Toronto, and Harvard University, said Science Daily.

We have reported that the U.S. Food and Drug Administration (FDA) was examining the results of a study on Aricept, which examined 974 patients suffering from dementia.  There were 11 deaths among patients taking Aricept as compared to no deaths occurring among those taking the placebo. Medical experts say that the study should not be written off and that it might indicate that Aricept and similar drugs increase the risks of heart disease, according to a prior New York Times report. Also, data from two clinical trials indicated that people taking Reminyl (Generic: Galantamine) have a much higher death rate than those taking a placebo. The trials, involved approximately 2,000 patients in 16 countries.

Anticholinergic drugs are a commonly prescribed group of drugs prescribed for the treatment of a variety of diseases and conditions, including acid reflux, Parkinson’s Disease, and urinary incontinence. Anticholinergic drugs work by stopping acetylcholine—a chemical that enhances communication between nerve cells in the brain—from binding to its receptors in nerve cells.

In the first Wake Forest study, older adults taking anticholinergic medications became more likely to walk more slowly and required help in other daily activities.  "These results were true even in older adults who have normal memory and thinking abilities," said study author Dr. Kaycee M. Sink. "For older adults taking a moderately anticholinergic medication, or two or more mildly anticholinergic medications, their function was similar to that of someone three to four years older."  Sink is an assistant professor of internal medicine-gerontology at Wake Forest University.

Common anticholinergic medicines mentioned in the review included the blood pressure medication nifedipine (Adalat or Procardia), the stomach antacid ranitidine (Zantac), and the incontinence medication tolterodine (Detrol).  The study involved over 3,000 people who were an average of 78 years of age.  The study’s findings were scheduled to be presented this Saturday at the American Geriatrics Society annual meeting, taking place in Washington, D.C.

In the second Wake Forest study, which was published online in April in the Journal of the American Geriatrics Society, Sink found that older nursing home residents who were taking medications for dementia as well as who were taking anticholingerics for incontinence experienced function decline at a rate of 50 percent faster than those patients who were only receiving drug therapy treatment for dementia.  The patients studied completed at least two consecutive prescriptions for cholinesterase inhibitors—a grouping of drugs used to treat dementia by increasing levels of acetylcholine—that include donepezil (Aricept), glantamine (Razdyne), rivatigmine (Exelon), and tacrine (Cognex). 

About 10 percent of those patients studied were also taking either oxybutynin or tolterodine, the two most commonly prescribed drugs for urinary incontinence.  "Over a year's time, the decline we observed would represent a resident going from requiring only limited assistance in an activity to being completely dependent, or from requiring only supervision to requiring extensive assistance in an activity," said Sink.  "The two drugs are pharmacological opposites, which led us to hypothesize that the simultaneous treatment of dementia and incontinence could lead to reduced effectiveness of one or both drugs, Sink said.

Alarmingly, an estimated 33 percent of people with dementia are also taking a medication to control incontinence.  The two studies suggest that physicians should carefully consider the implications when prescribing anticholinergic medications to older adults.

Donepezil, rivastigmine, and galantamine are known as cholinesterase inhibitors and inhibit the enzyme that breaks down acetylcholine, a brain transmitter. A deficiency of acetylcholine has been thought to play a role in Alzheimer’s disease.

The BMJ review identified 22 published studies that tested the use of these three drugs in the treatment of Alzheimer’s disease. No study found anything more than a minimal benefit with respect to any of the drugs when compared to a placebo.

As a result, the authors concluded: “Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer’s disease is questionable.”

The authors also found that “donepezil, rivastigmine, and galantamine caused a broad spectrum of adverse events nausea, vomiting, diarrhea, and weight loss were the most common.”

Public Citizen has been a critic of ARICEPT since as far back as 1997 and noted that the three drugs accounted for over $861 million in sales in 2004 not because “evidence of either the effectiveness or safety of these drugs, but is rather a testament to the marketing skills of the drug industry, aimed at consumers and prescribers.”

The group concluded that the “very successful strategy to sell Alzheimer’s disease drugs is based on hope, fear, and guilt: hope that one of these drugs might ‘work,’ fear that if one of these drugs is not started quickly all will be lost, and guilt if family members have not made the decision to ‘fight’ the disease with these expensive, minimally effective drugs.”

As is often the case with prescription medications that have been approved for a specific or limited purpose, however, a manufacturer will seek to gain approval for one or more additional uses that will significantly boost the revenue generated by a particular drug.

That was the case with ARICEPT (marketed jointly by Pfizer, Inc. and Eisai Co.) when testing began in connection with an application to have the drug approved for the treatment of vascular dementia, a widespread form of cognitive decline that results from narrowing and blockage of arteries that supply blood to the brain.

The test, however, raised some serious concerns about both the effectiveness and the safety of ARICEPT.

Although the Phase 3 clinical trial found ARICEPT was no better than a placebo in improving the overall functioning of patients with vascular dementia, Eisai claims that the drug did improve cognitive function.

Critics, who believe the drug is also not effective in the treatment of Alzheimer’s, were even more concerned over the fact that 11 (of 648) patients given ARICEPT once a day for 24 weeks, died. None of the 326 patients who took a placebo died.

Such a major discrepancy in mortality rates between two test groups is statistically significant and is therefore unlikely to be a chance occurrence.

Eisai claims that the deaths do not change the risk profile of the drug. Pfizer has not taken a position on the issue. Nevertheless, some experts see the results as a “red flag” that should raise some concern as to the approval of the application now before the FDA to expand the use of ARICEPT.  The drug is currently approved for vascular dementia in six smaller markets. U.S. approval, however, who significantly, boost.

The trial was limited to patients with vascular dementia and no prior diagnosis of Alzheimer's disease. Most of the subjects had a history of stroke or heart disease and were also taking medications for their cardiovascular problems.

Since there had been a combined 2% incidence of death in the placebo groups from two previous vascular dementia tests, and given the overall age and health problems of the subjects in this trial, Eisai had not expected the absence of deaths in the placebo group.

Eisai claims the 1.7% incidence of death in this ARICEPT group was similar to that in prior trials. In those trials, however, the difference between placebo and ARICEPT deaths had not been statistically significant.

Although the ARICEPT group in the latest test showed a statistically significant improvement in cognitive function when compared to those taking placebos, the ARICEPT group showed no significant benefit with respect to “global function,” another primary measure of the trial.