SOURCE: Cummings J, et al. Effect of dextromethorphan-quinidine on agitation patients with Alzheimer disease dementia: A randomized clinical trial. JAMA 2015;314:1242-1254.
First-line management of agitation in persons with dementia is supposed to be non-pharmacologic. When this is insufficient to adequately manage agitation, atypical antipsychotics have been often used, but the recognition that such agents are associated with increased mortality has dampened enthusiasm for their use. A trial of citalopram was promising, but the adverse effect of potential QT prolongation remains a concern. The idea to use a combination of dextromethorphan and quinidine for agitation stems from the approval of this same combination for treatment of pseudobulbar affect. Pseudobulbar affect, which is sometimes colloquially called “emotional hyperlability syndrome,” is typified by outbursts of exaggerated or inappropriate positive (e.g., laughing) or negative (e.g., crying) emotions. A patient might burst into uncontrolled sobbing because he or she discovered his or her shirt was not buttoned properly. Since agitation syndromes are also emotion-laden, might the combination of dextromethorphan and quinidine work here?
Cummings et al randomized patients assessed to have probable Alzheimer’s disease and a history of agitation to the combination of quinidine and dextromethorphan or placebo for 10 weeks. Aggression scores were substantially improved compared to placebo. Adverse events leading to discontinuation were infrequent (5.3% on the quinidine-dextromethorphan combination, 3.1% on placebo). The combination of dextromethorphan and quinidine appears promising for management of aggression in Alzheimer’s patients.
The combination of dextromethorphan and quinidine appears promising for management of aggression in Alzheimer’s patients.
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