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Comment & Response
March 15, 2016

Dextromethorphan-Quinidine for Agitation in Alzheimer Disease

Author Affiliations
  • 1Division of Geriatrics, University of California, San Francisco
JAMA. 2016;315(11):1166. doi:10.1001/jama.2015.18286

To the Editor Behavioral complications of dementia can be highly distressing, and new interventions to treat this condition are needed. However, several aspects of the trial on the effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia by Dr Cummings and colleagues1 caused us concern.

First, the increase in falls associated with use of dextromethorphan-quinidine (8.6% for dextromethorphan-quinidine vs 3.9% for placebo) was substantial and calls into question the conclusion that the drug was “generally well tolerated.” Although the finding of excess falls may have been due to chance or an imbalance in baseline characteristics between the intervention and control groups, this effect should be presumed real until proven otherwise. This interpretation is supported by previous randomized trials of dextromethorphan-quinidine for pseudobulbar affect, in which rates of dizziness were consistently and markedly higher in the active treatment group, although data on falls were conflicting.24

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