If you're considering pharmacological therapy for a patient with dementia, be aware that there's only modest evidence of clinically meaningful benefit for the average patient. Therefore, conduct an individualized assessment of your patient and his or her situation, in consultation with caregivers, to determine if a trial of drug therapy is appropriate. If you decide to prescribe, choose one of the five FDA-approved drugs for dementia based on cost, ease of use, tolerability and side effects, because currently there's no convincing evidence that any one of the drugs is more effective than another.
AAFP-ACP Guideline Looks at Drug Treatment of Dementia
Available Drugs' Effectiveness Unclear; More Research Needed
By Paula Haas Binder
3/5/2008
That's the gist of a new clinical practice guideline on pharmacological treatment of dementia from the AAFP and the American College of Physicians, or ACP. The guideline appears in the March 4 Annals of Internal Medicine. The types of dementia covered in the guideline include dementia related to Alzheimer's disease and vascular dementia.
The guideline was developed under the auspices of the AAFP Commission on Science.
"With the aging population in the United States, dementia has become an important public health problem," the guideline notes. "The prevalence of Alzheimer's disease is projected to quadruple in the next 50 years to 1 in 45 Americans. In addition, the long duration, caregiver burden and costs associated with providing care contribute to making dementia a major health care problem."
The AAFP-ACP guideline panel reviewed the medical literature and found limited evidence regarding the effectiveness of the five approved drugs in regard to these outcomes: cognition, global function, behavior/mood, and quality of life/activities of daily living. The five drugs are the cholinesterase inhibitors donepezil (Aricept), galantamine (Nivalin, Razadyne, Reminyl), rivastigmine (Exelon) and tacrine, and the neuropeptide-modifying agent memantine (Namenda).
The guideline panel found that some clinical trials showed statistically significant improvements in dementia patients treated with one or another of these medications. The problem is that "those improvements often weren't clinically significant," says panelist Kenneth Schellhase, M.D., M.P.H., director of research and assistant professor in the family and community medicine department at the Medical College of Wisconsin, Milwaukee. Schellhase was a member of the AAFP Commission on Science when he was appointed to the panel.
"The magnitude of improvement in those trials often was so small that patients or their caregivers may not be interested in exposing the patient to the potential side effects of the drug for such a modest benefit," Schellhase says. "And for patients and physicians who do choose a trial of therapy, there is little evidence to guide the duration of treatment."
The guideline was developed under the auspices of the AAFP Commission on Science.
"With the aging population in the United States, dementia has become an important public health problem," the guideline notes. "The prevalence of Alzheimer's disease is projected to quadruple in the next 50 years to 1 in 45 Americans. In addition, the long duration, caregiver burden and costs associated with providing care contribute to making dementia a major health care problem."
The AAFP-ACP guideline panel reviewed the medical literature and found limited evidence regarding the effectiveness of the five approved drugs in regard to these outcomes: cognition, global function, behavior/mood, and quality of life/activities of daily living. The five drugs are the cholinesterase inhibitors donepezil (Aricept), galantamine (Nivalin, Razadyne, Reminyl), rivastigmine (Exelon) and tacrine, and the neuropeptide-modifying agent memantine (Namenda).
The guideline panel found that some clinical trials showed statistically significant improvements in dementia patients treated with one or another of these medications. The problem is that "those improvements often weren't clinically significant," says panelist Kenneth Schellhase, M.D., M.P.H., director of research and assistant professor in the family and community medicine department at the Medical College of Wisconsin, Milwaukee. Schellhase was a member of the AAFP Commission on Science when he was appointed to the panel.
"The magnitude of improvement in those trials often was so small that patients or their caregivers may not be interested in exposing the patient to the potential side effects of the drug for such a modest benefit," Schellhase says. "And for patients and physicians who do choose a trial of therapy, there is little evidence to guide the duration of treatment."
Dementia Guideline Panel Recommendations
Recommendation 1: Clinicians should base the decision to initiate a trial of therapy with a cholinesterase inhibitor or memantine on individualized assessment. (Grade: weak recommendation, moderate-quality evidence.)
Recommendation 2: Clinicians should base the choice of pharmacological agents on tolerability, adverse effect profile, ease of use and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacological agents for the treatment of dementia. (Grade: weak recommendation, low-quality evidence.)
Recommendation 3: There is an urgent need for further research on the clinical effectiveness of pharmacological management of dementias.
Recommendation 2: Clinicians should base the choice of pharmacological agents on tolerability, adverse effect profile, ease of use and cost of medication. The evidence is insufficient to compare the effectiveness of different pharmacological agents for the treatment of dementia. (Grade: weak recommendation, low-quality evidence.)
Recommendation 3: There is an urgent need for further research on the clinical effectiveness of pharmacological management of dementias.
The bottom line is to have a conversation with caregivers and with the patient, if possible, to arrive at an individualized decision. "Don't use these drugs on a blanket basis," Schellhase says. "Benefits are modest, cost is significant, and side effects can be substantial. If you do decide to use a drug, choose the drug that is least expensive for the patient."
Given the lack of clear and substantial benefits, the guideline "can help family doctors feel OK about not pushing patients and family members to try these drugs, and it can help family members feel OK if they decide against using the drugs," Schellhase adds.
The guideline also issues an urgent call for more research. That research should further evaluate the effectiveness of drug therapy and assess whether treatment affects outcomes such as institutionalization. In particular, it should look at the appropriate duration of therapy, provide head-to-head drug comparisons and test combination therapy.
Given the lack of clear and substantial benefits, the guideline "can help family doctors feel OK about not pushing patients and family members to try these drugs, and it can help family members feel OK if they decide against using the drugs," Schellhase adds.
The guideline also issues an urgent call for more research. That research should further evaluate the effectiveness of drug therapy and assess whether treatment affects outcomes such as institutionalization. In particular, it should look at the appropriate duration of therapy, provide head-to-head drug comparisons and test combination therapy.
