CLINICAL QUESTION: What’s the clinical effectiveness and safety profile of mirtazapine in reducing agitation in dementia relative to placebo?
BACKGROUND: Nonpharmacological treatments are considered first-line for the management of agitation in patients with dementia. When these treatments are ineffective, pharmacological treatments are sometimes used with caution because of their high side effect profile and low efficacy. Mirtazapine works as a centrally acting alpha-2, 5-HT1 and H1-antagonist and therefore has sedative properties. It also has less anticholinergic activity in comparison to other antidepressants and minimal effects on the cardiovascular system, suggesting it might have a more favorable side effect profile.
STUDY DESIGN: Multi-center, parallel-group, double-blind, placebo-controlled randomized trial
SETTING: 26 United Kingdom National Health Service clinical centers
SYNOPSIS: 204 patients with probable or possible Alzheimer’s disease with coexisting agitation who did not respond to non-pharmacological strategies participated in the study. Patients were randomized 1:1 into either the mirtazapine (titrated to 45 mg daily) or placebo group. The mean overall dosage in the mirtazapine group was 30.5 mg daily. At six weeks, the severity of agitation (determined by the Cohen-Mansfield Agitation Inventory (CMAI) score) decreased in both the mirtazapine (71.1 ±16.4 to 61.4 ±23.5) and placebo (69.8 ±17.1 to 60.0 ±19.9) groups, but this was not statistically significant. At 12 weeks, the CMAI score decreased in both the mirtazapine (71.1 ±16.4 to 61.4 ±22.6) and placebo (69.8 ±17.1 to 60.8 ±21.8) groups, but this was not statistically significant. The number of adverse events was similar in both the control and mirtazapine group at approximately 65%. They also found there were more deaths in the mirtazapine group (seven deaths) versus the placebo group (one death) by week 16.
BOTTOM LINE: Mirtazapine was no more effective than placebo for the treatment of agitation in dementia and may be associated with a higher risk of death.
CITATION: Banerjee S, et al. Study of mirtazapine for agitated behaviors in dementia (SYMBAD): a randomized, double-blind, placebo-controlled trial. Lancet. 2021;398(10310):1487-1497. doi:10.1016/S0140-6736(21)01210-1.
Ms. Whalen is a nurse practitioner at Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, N.C.