1 Centre Hospitalier de L'Universite de Montreal - Pharmacy, 1000, St-Denis, Montreal, Québec H2X 0C1, Canada.
2 Centre Hospitalier de l'Université de Montréal Centre de Recherche - Neurosciences, Québec H2W 1T8, Canada.
3 Concordia University - Health, Kinesiology and Applied Physiology, Montreal, Québec, Canada.
4 Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Montreal, Québec, Canada.
5 Université du Québec en Outaouais - Psychology, Gatineau, Québec, Canada.
6 Université du Québec à Trois-Rivières - Psychology, Trois-Rivières, Québec, Canada.
7 Centre Hospitalier de l'Université de Montréal - Geriatrics, 1000, RUE SAINT-DENIS Montréal, Montreal, Québec H2X 0C1, Canada.
8 Institut universitaire de gériatrie de Montréal - Centre de recherche, Montreal, Québec, Canada.
9 Centre Hospitalier de l'Université de Montréal - Geriatrics, 1000, rue Saint-Denis, Montreal, Québec H2X 0A9, Canada.
10 Centre Hospita

Background: Mirtazapine promotes sleep by blocking serotonin and histaminergic receptors and is often used off-label to treat chronic insomnia. However, its efficacy remains to be demonstrated in a clinical trial. The MIRAGE study aims to determine the efficacy and safety of mirtazapine in older patients with chronic insomnia.

Methods: This was a double-blind, randomised, placebo-controlled trial in a geriatric outpatient clinic of a teaching hospital. Adults aged 65 years and older with chronic insomnia were included. Sixty participants were randomised in a 1:1 ratio to receive mirtazapine 7.5 mg or a matching placebo for 28 days. The primary efficacy endpoint was the mean change in the Insomnia Severity Index (ISI) score from baseline to 28 days post-treatment. The primary safety endpoints included any adverse events reported during the clinical trial and all adverse events leading to premature discontinuation.

Results: Mirtazapine was superior to placebo on the primary outcome measure, subjective wake after sleep onset, total sleep time and sleep efficiency. After 28 days, the mean change in ISI score was significantly greater in the mirtazapine group (-6.5 [95%CI; -8.3 to -4.8]) compared to the placebo group (-2.9 [95%CI; -4.4 to -1.4]), with a p-value of 0.003. No participant experienced severe adverse events. A total of 6 participants in the mirtazapine group and 1 participant in the placebo group discontinued their treatment due to adverse events.

Conclusion: Mirtazapine reduces chronic insomnia symptoms in older people. However, its use may be limited by mild but clinically relevant adverse events. (clinicaltrials.gov NCT05247697).

Impact statement: This is the first randomised, double-blind, placebo-controlled trial on the efficacy and safety of Mirtazapine in older adults with chronic insomnia. Our findings show that a 28-day treatment with mirtazapine, compared to placebo, significantly reduces insomnia severity, as measured by the Insomnia Severity Index. Despite the current lack of robust evidence, mirtazapine is widely prescribed by clinicians to treat insomnia in older adults with chronic insomnia. Publishing our study will facilitate the broad dissemination of this critical information, helping clinicians more effectively treat their older patients.