Mirtazapine for agitation in dementia: moving forward

Alzheimer's disease is a progressive and fatal neurodegenerative disorder with a worldwide prevalence estimated at 25–37 million. 1 WHOFact sheets: dementia. 2020. https://www.who.int/news-room/fact-sheets/detail/dementia Google Scholar Although Alzheimer's disease is clinically characterised by cognitive impairments and functional deficits, agitation is a particularly common symptom 2 Zhao QF Tan L Wang HF et al. The prevalence of neuropsychiatric symptoms in Alzheimer's disease: systematic review and meta-analysis. J Affect Disord. 2016; 190: 264-271 Crossref PubMed Scopus (498) Google Scholar and associated with excess disability, increased institutionalisation, and diminished quality of life. 3 Antonsdottir IM Smith J Keltz M Porsteinsson AP Advancements in the treatment of agitation in Alzheimer's disease. Expert Opin Pharmacother. 2015; 16: 1649-1656 Crossref PubMed Scopus (26) Google Scholar There is an urgent and unmet need for efficacious treatments for agitation. Over the past decade, efforts have included trials using citalopram, 4 Porsteinsson AP Drye LT Pollock BG et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014; 311: 682-691 Crossref PubMed Scopus (380) Google Scholar dextromethorphan, 5 Cummings JL Lyketsos CG Peskind ER et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA. 2015; 314: 1242-1254 Crossref PubMed Scopus (138) Google Scholar brexpiprazole, 6 Grossberg GT Kohegyi E Mergel V et al. Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's dementia: two 12-week, randomized, double-blind, placebo-controlled trials. Am J Geriatr Psychiatry. 2020; 28: 383-400 Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar and nabilone. 7 Herrmann N Ruthirakuhan M Gallagher D et al. Randomized placebo-controlled trial of nabilone for agitation in Alzheimer's disease. Am J Geriatr Psychiatry. 2019; 27: 1161-1173 Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trialThis trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. Full-Text PDF Open Access