Primary Care Panel Finds Dementia Drugs to be Peas in a Pod

By Charles Bankhead
PHILADELPLHIA, March 4 -- Two big groups of primary care physicians sat down to sort out the solid evidence for choosing and using drug therapy for dementia and found little to sort.
"No convincing evidence demonstrates that one therapeutic treatment is more effective than another," said the authors of a joint clinical guideline on treatment of dementia by the American College of Physicians and the American Academy of Family Physicians.
The guideline recommendations were reduced to generalities about individualized patient assessment and consideration of each drug's characteristics.
Even there, the recommendations have only weak supporting evidence, reflecting the "urgent need" for more research on the effectiveness of drug therapy for dementia, Amir Qaseem, M.D., Ph.D., of the American College of Physicians, and co-authors wrote in the March 4 issue of Annals of Internal Medicine.
"Because few trials compare one drug with another, evidence about effectiveness is insufficient to support the choice of specific drugs for treatment of dementia," said members of the Joint ACP/AAFP Panel on Dementia. "Therefore, tolerability, adverse effect profile, ease of use, and cost of medication are reasonable criteria to help select a treatment."
The guideline and recommendations evolved from the panelists' review of evidence for the effectiveness of the five FDA-approved medications for dementia: the cholinesterase inhibitors donepezil (Aricept), galantamine (Reminyl), rivastigmine (Exelon), and tacrine (Cognex), and the neuropeptide modifier memantine (Namenda).
In examining the evidence, the panel evaluated clinically important treatment effects, as well as statistically significant effects. For each drug, they sought to answer two questions.
Does the drug improve cognitive symptoms and outcomes?
What is the evidence for efficacy in the treatment of dementia?
The summary findings for each agent were:
Donepezil. The average change in cognitive score was statistically significant but not clinically important. Some, but not all, studies found improvements in activities of daily living scores for patients with Alzheimer's disease and vascular dementia with no adverse effects. The duration of all but one trial was less than one year.
Galantamine. Pooled evidence showed statistically significant improvement in cognition, but not clinical improvement. Three individual studies suggested a beneficial effect in certain subgroups. The duration of trials was less than one year.
Rivastigmine. Cognitive improvement did not reach statistical significance, but clinically important improvement occurred on a global assessment. Behavior and quality-of-life outcomes did not significantly improve. The duration of trials was less than seven months.
Tacrine. The evidence did not substantiate a beneficial effect on cognition or behavior, except for a global assessment in two studies. The evidence also demonstrated a risk of serious adverse effects, including liver damage.
Memantine. Studies demonstrated statistically significant improvement in cognition scores, but the panel found inadequate evidence of clinically important improvement.
Although the five drugs demonstrated significant improvement on various dementia scales, most of the outcomes are not applicable to routine clinical practice, the ACP/AAFP panel said. Effects on quality of life were mixed. Most studies had a treatment duration of less than one year.
Co-author Vincenza Snow, M.D., disclosed financial relationships with Novo Nordisk, Bristol-Myers Squibb, Boehringer-Ingelheim, and Endo Pharmaceuticals. None of the other co-authors had disclosures involving commercial interests.
Additional source: Annals of Internal MedicineSource reference: Qaseem A, et al. "Current pharmacologic treatment of dementia: A clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians." Ann Intern Med 2008; 148: 370-378.