Mirtazapine does not reduce agitated behaviors in persons with dementia (SYMBAD)

Reference

Banerjee S, High J, Stirling S, et al. Study of mirtazapine for agitated behavior in dementia (SYMBAD): a randomized, double-blind, placebo-controlled trial. Lancet 2021;398(10310):1487-1497

Synopsis

This was a well-designed randomized controlled trial of mirtazapine versus placebo (N = 204) for the treatment of agitation among people with dementia. It was conducted in 26 UK National Health Service clinical centers over 12 weeks. Participants were enrolled if they met the criteria from the National Institute of Neurological and Communicative Diseases and Stroke – Alzheimer’s Disease and Related Disorders Association for probable or possible Alzheimer’s disease and had coexisting agitation defined as a Cohen-Mansfield Agitation Inventory (CMAI) score of at least 45. The investigators also required that the agitated behaviors had not responded to nonpharmacological management. Potential participants were excluded if they were considered too unwell (eg, suicide risk), had medical contraindications, or did not have a family or professional caregiver to provide information. The target dose was 45 mg daily of mirtazapine, three 15-mg capsules in one daily dose or identical-appearing placebo. The authors started with one capsule daily and increased by one capsule daily in weeks 2 and 3, as tolerated. They allowed additional titration as needed. Analysis was by intention to treat. Adequate clinical response was considered to be improvement by at least 6 points on the CMAI at the 12-week follow-up. The mean dose in the treated group was 30.5 mg. The severity of agitation improved in both groups over time and at no point reached a statistically significant difference. Caregiver burden was not lower in the treated group at any point, including no difference in anxiety. There were several more deaths in the treated group (7 vs 1), but the study was not powered to assess this outcome.