Case series of perimenopausal women with insomnia treated with mirtazapine followed by prolonged-release melatonin add-on and monotherapy

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The sedating antidepressant mirtazapine is used off label for insomnia in perimenopausal women. Despite its apparent efficacy, mirtazapine causes significant increases in appetite and weight gain. Prolonged-release melatonin (PRM) is approved for primary insomnia in patients aged 55 years and older. A clinical experience with PRM add-on to mirtazapine in facilitating mirtazapine withdrawal while maintaining improved sleep quality and abrogating weight gain in perimenopausal women with insomnia is described.


Eleven perimenopausal women (ages 45–52; FSH = 53 ± 8; normal BMI, 22.9 ± 0.6) with insomnia, who do not suffer from depression as assessed by the Hamilton scale, were treated with 15 mg mirtazapine (Remeron®) for 2–4 weeks. PRM, 2 mg (Circadin®), was then added on, and mirtazapine was tapered off for another 1–3 months. Prospective data on body weight and subjectively assessed sleep quality and well-being (assessed by the Pittsburgh Sleep Quality Index, PSQI, and Well-Being Index, WHO-5, respectively) were collected before, during, and at the end of the treatment.


Sleep quality ratings improved significantly (by 103% on average) during combined mirtazapine and PRM intake and 180% during subsequent intake of PRM alone or together with very low doses of mirtazapine (P < 0.05 for all). Well-being significantly improved by 83% during the treatment. Seven of 11 women demonstrated weight gain following mirtazapine intake, five of whom have started to reduce weight following mirtazapine withdrawal and PRM intake. No adverse events were reported.


Application of mirtazapine followed by PRM add-on and monotherapy improves sleep in perimenopausal women while evading mirtazapine-induced weight gain. These results warrant further investigation of a larger population in controlled clinical trials.

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