Mirtazapine not effective in treating agitation in patients with dementia

1. Compared to placebo, mirtazapine did not significantly reduce agitation in patients with dementia.

2. There was no significant difference in the number of adverse events experienced between the two groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Behavioural symptoms affect up to 90% patients with dementia and can be a source of significant stress to family and caregivers. One of the most common neuropsychiatric symptoms is agitation. Mirtazapine is a noradrenergic and specific serotonergic agent commonly prescribed as an antidepressant in the geriatric patient population. While some studies have suggested a potential benefit of mirtazapine on neuropsychiatric symptoms, the evidence is limited. In this randomized control trial, mirtazapine was compared to placebo in 204 patients with dementia. Patients were treated for 12-weeks and evaluated half-way, at 12-weeks and at 16-weeks for withdrawal symptoms. The results of this study showed there was no benefit of mirtazapine compared to placebo in lowering agitation. There was also no major difference in adverse events and deaths related to the medications given between the two groups. Limitations of this study included disruptions by the COVID-19 pandemic on data collection. Unfortunately, this study does not provide a beneficial option for treating agitation symptoms in dementia; however, the negative result will help guide medical practitioners and researchers in finding alternatives.

Click to read the study in the Lancet

Click to read an accompanying editorial in the Lancet

Relevant Reading: Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions

In-Depth [randomized controlled trial]: This parallel-group, double-blind, placebo-controlled, randomized-control trial was done on 204 patients with dementia. However, due to patient withdrawal of consent and death, there was only n=81 patients in the mirtazapine group and n=90 patients in the placebo group. There were also more female patients in the mirtazapine group (75%) then placebo group (58%). The average age of both groups was around 82.5 years of age. Patients were treated for 12-weeks with follow-up at 6, 12, and 16-weeks. The primary outcome was measured by the Cohen-Mansfield Agitation Inventory (CMAI) which was assessed by the caregivers and the patients themselves. Secondary outcomes were also measured such as quality of life and carer mental health. Safety was measured by death, withdrawal (up to 4 weeks after last dose), adherence, adverse events, and the Suicide rating scale. In both groups, agitation decreased over the 12-weeks from baseline scores. However, there was no significant difference in the effect of mirtazapine over the placebo (adjusted mean difference -1.74 [95% CI -7.17-3.69], p=0.53). There was also no significant difference in the secondary outcomes, except for a higher carer burden in the mirtazapine group at 12 weeks (p=0.020). Analysis between the groups showed weak evidence (p=0.065) of a difference in mortality between the groups, despite more patients having died in the mirtazapine group at 16-weeks (n=7 versus n=1). There were more serious adverse events in the placebo group, but this was also not statistically significant.

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