An accompanying editorial notes that agitation is one of the most frequent and clinically important neuropsychiatric symptoms seen among patients with Alzheimer’s disease. Effective treatment options are limited; current practice guidelines promote non-pharmacological interventions as the first-line approach however patients with severe symptoms may require pharmacological interventions. Atypical antipsychotics are used off-label in this setting but are associated with significant safety concerns.
The author comments that the results of this study are encouraging and that it had several strengths including its sequential parallel comparison design, which aimed to minimise the placebo response. However there were a number of limitations, including focus on the single Neuropsychiatric Inventory domain (for which a clinically important difference has not been established). Although the adverse event profile with dextromethorphan quinidine seemed much better than with atypical antipsychotics, the editorial notes that the significant detrimental effects of the latter only became evident from meta-analysis. More research is therefore required.
Dextromethorphan-quinidine was licensed in the EU in 2013 for the treatment of pseudobulbar affect. Dextromethorphan is a sigma-1 receptor agonist and NMDA antagonist; quinidine (CYP2D6 inhibitor) is used to increase its plasma levels. The authors of the editorial discuss the emerging evidence for other treatment approaches for agitation in dementia, and they comment that “pending further evidence, there is a reasonably strong case to prioritise dextromethorphan-quinidine as an off-label treatment for agitation, possibly as a safer alternative to atypical antipsychotics. However, while further studies are conducted to verify the efficacy and safety of this approach, it will be important to achieve a robust international expert consensus regarding the prioritization of potential treatments for agitation in patients with dementia to improve the consistency of clinical practice.”