Cholinesterase inhibitors and memantine are not one-size-fits-all drugs that can be prescribed to every patient with dementia and should only be employed after assessing each drug's risk/benefit profile in light of an individual patient's needs, according to a new set of clinical guidelines.
"The most important thing to keep in mind is that there is no cure for dementia," said Dr. Amir Qaseem, author of the guidelines and a member of the Joint American College of Physicians/American Academy of Family Physicians Panel on Dementia.
"These drugs can only alleviate symptoms and may slightly delay progression. But they should not be prescribed to every dementia patient because the benefits are very modest and some patients may not show benefit at all, and all the drugs carry potential harms."
Although many patients do show statistically significant improvements while taking the drugs, most of those changes are small and not clinically meaningful, according to the guidelines (Ann. Intern. Med. 2008;148:370-8).
The panel also concluded that there is insufficient evidence to recommended one drug over another for the treatment of dementia. Instead, "the choice of therapy should be based on an evaluation of adverse events, tolerability, and cost, because there is no evidence that one treatment is more effective than another," Dr. Qaseem said in an interview.
The recommendations are particularly important for primary care physicians, who care for most patients with dementia, said Dr. William Thies, vice president of medical and scientific affairs for the Alzheimer's Association.
"The bulk of dementia patients are being managed by primary care physicians, and this is only going to increase as we deal with the oncoming tidal wave of Alzheimer's patients over the coming decades," he said in an interview. "As these guidelines point out, the emphasis when treating these patients should be that the physician, patient, and family work together as a unit to decide the best use of a medication and also, the best time to stop."
The guidelines panel mined data from 59 studies that examined any of the five drugs approved for dementia treatment in the United States (donepezil, rivastigmine, galantamine, tacrine, and memantine). Drugs were assessed for their effects on symptoms (cognition, function, and behavior), quality of life, and their adverse event profile. The results of this evidence review accompany the guidelines (Ann. Int. Med. 2008; 148:379-97).
The largest body of high-quality evidence was seen for donepezil: Twenty-four studies compared it with either placebo or vitamin E. Most showed statistically significant effects in favor of the drug for at least one measure of cognition. Improvements in function also were reported. Nine studies also showed that these improvements were clinically meaningful. "These findings are important because although the average improvement in cognition...did not reach statistical significance, a subset of patients may have clinical improvement," the panel noted. Up to 57% of patients discontinued their donepezil because of adverse events; the most commonly reported were gastrointestinal upset and muscle cramps.
Ten studies examined the use of galantamine. The drug was associated with statistically significant, but not clinically important, improvements in cognition and behavior. Withdrawal because of adverse events ranged from 8% to 57%, with the most common being gastrointestinal symptoms, eating disorders, weight loss, and dizziness.
Rivastigmine was assessed in nine placebo-controlled studies. Overall, there was significant but very inconsistent cognitive benefit, and no significant benefits on behavior or quality of life. Up to 29% of patients withdrew because of adverse events including dizziness, nausea and vomiting, diarrhea, weight loss, and headache. …