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.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Geriatrics | |
A relevant problem, but this study adds only a bit to the literature. The finding of benefit for insomnia treatment is somewhat helpful in confirming current off-label practice, but the trial was too small to meaningfully exclude adverse effects. I'm glad there were no serious adverse events, but the fact that 6x more participants stopped mirtazapine than stopped placebo, points to a need for further investigation with a larger study.
I can't get that interested in a drug-vs-placebo study for insomnia. We have other active therapies, both drug and nonpharmacologic, and I would want to see a comparative effectiveness study.
Practical clinical trial about a common complaint in older adults: inadequate sleep.
The drug is already used widely as a sleep aid, so more data on efficacy is useful; however, this is a very small study, and the MMSE scores suggest no significant cognitive impairment. Side effects might be more severe if the medication is used with cognitively impaired patients (which is already happening in my community).
Managinf insomnia in older adults is often challenging. This RCT provides evidence for pharmacotherapy of chronic insomnia symptoms with mirtazapine, including the occurrence of side effects in 79% of those treated.
