Mirtazapine for Older Adults’ Insomnia: The MIRAGE Trial

If mirtazapine comes up at an insomnia appointment, ask what improvement would justify continuing it and what would trigger a review.

What changed during treatment?

The 2025 MIRAGE trial randomized 60 older adults, including 36 women, to 7.5 mg nightly or placebo for 28 days. Three assigned mirtazapine never started; analyses included 27 treated participants versus 30 receiving placebo.¹

On the 0–28 Insomnia Severity Index, adjusted average reductions were 6.5 versus 2.9 points, with lower scores better. Sleep diaries also favored mirtazapine for time awake after falling asleep. Actigraphy, the movement-based device measurements, showed no significant between-group sleep differences.¹

What limits the result?

Adverse events caused six of 27 mirtazapine users versus one of 30 placebo users to discontinue. Reasons included daytime drowsiness and confusion. Missing follow-up weakens confidence, although a sensitivity analysis assuming no improvement for missing participants still favored treatment. Four weeks cannot establish lasting benefit or safety. The Quebec Research Network on Ageing funded the trial.¹

How should a prescribing conversation use this?

The US REMERON label approves mirtazapine for major depressive disorder in adults. Insomnia treatment is off-label. The label warns about sleepiness affecting driving, increased appetite and weight gain. Older people may develop confusion, excessive sedation or low sodium; medicines such as diuretics can increase sodium concerns. Avoid combining it with alcohol or benzodiazepines. Discuss the full medication list with the prescriber, including medicines taken only occasionally.²

If stopping becomes appropriate, agree a gradual dose-reduction plan. The label recommends tapering rather than abrupt cessation.²

NHLBI³ describes cognitive behavioral therapy for insomnia, CBT-I, as the usual first treatment for long-term insomnia, commonly delivered over six to eight weeks.³ Ask whether it is available alongside the medication discussion. Our CBT-I explanation describes the approach.

The “Notice It” section of Did I Do That in My Sleep? offers a 14-Night Lights-Out Record for approximate morning observations and daytime effects. Add a brief note about alertness and activities affected; use the clinician’s diary if they request one. Do not wait to finish a record before reporting a troublesome side effect.