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Pharmacologic Treatment of Dementia

Drugs do not lead to dramatic improvements in patients with dementia.

The American College of Physicians and the American Academy of Family Physicians have published a clinical practice guideline on pharmacologic therapies for dementia. The guideline is based on a review of 59 randomized trials of five FDA-approved drugs (donepezil, galantamine, rivastigmine, tacrine, and memantine) in more than 16,000 patients. The guideline concludes that evidence is insufficient to compare the drugs for effectiveness, and it recommends the following:

• Base decisions about starting a cholinesterase inhibitor on individualized assessments.
  
• Base the choice of pharmacologic agent on tolerability, adverse effects, ease of use, and cost.
  
• Further research on effectiveness of the medications alone and in combination for clinical outcomes is required.
  

Both clinical recommendations are rated "weak" (meaning the benefits are finely balanced with risks and burdens) and based on low- to moderate-quality evidence. The studied drugs show significant improvements in scores on various instruments (measuring cognition and global function), but clinical importance is less clear. Improvements can be clinically important for some patients, but they are unpredictable. Further, although the medications might help slow further decline, this goal might not be important in patients who already are judged to have poor quality of life. The guideline report adds that the severe side effects (gastrointestinal, hepatic) associated with tacrine make it an "unreasonable" choice.

Comment: This practice guideline, based on an extensive evidence review, reflects observations in clinical practice — in particular, that these medications do not lead to dramatic clinical improvements for dementia patients. In my view, development of new agents with more-meaningful clinical benefits should be a higher priority than further research on the currently available ones.

— Richard Saitz, MD, MPH, FACP, FASAM

Published in Journal Watch General Medicine March 25, 2008

Citation(s):

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 Mar 4; 148:370.

• Original article (Subscription may be required)
• Medline abstract (Free)

Raina P et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: Evidence review for a clinical practice guideline. Ann Intern Med 2008 Mar 4; 148:379.

• Original article (Subscription may be required)
• Medline abstract (Free)