REVIEW OF: Nguyen PV et al, Age Ageing 2025;54(3):afaf050

STUDY TYPE: Randomized, double-blind, placebo-controlled trial

Older adults often struggle with insomnia, and most hypnotic meds pose the risk of falls, confusion, or dependence. Mirtazapine is frequently prescribed off label for sleep, but until now, no high-quality trial had tested it in this age group.

In this 4-week study of 60 adults aged 65 and older with chronic insomnia, participants received mirtazapine 7.5 mg nightly or placebo. Mirtazapine led to larger improvements on the self-reported Insomnia Severity Index (ISI; -6.5 vs -2.9 with placebo) as well as improvement in total sleep time. About half of treated patients achieved a meaningful clinical improvement, and 40% achieved remission by self-report. Subjective measures from sleep diaries showed improvements in wake time and sleep efficiency. No difference was seen in secondary objective measures of sleep quality.

No severe adverse events occurred, but tolerability was an issue: Six people on mirtazapine (vs one on placebo) stopped early due to daytime drowsiness, confusion, or other mild side effects. Weight gain was minimal over the short term, and there were no falls or cardiac concerns.

CARLAT TAKE
Mirtazapine helped older adults feel that they slept better, but the benefit was modest—just past the “minimally important difference” of an ISI score drop of 6. And as with other sedatives, grogginess and confusion outweighed benefits for some. For patients who can’t access or don’t respond to cognitive behavioral therapy for insomnia, want to avoid standard hypnotics, or have comorbidities that mirtazapine addresses, a low bedtime dose is a reasonable option—just monitor for next-day sedation.