Mirtazapine for Insomnia

Guideline Recommendations and Evidence Quality

The American Academy of Sleep Medicine states that certain antidepressants, including mirtazapine, are used off-label for insomnia, but their efficacy for this indication is not well established, and they should be considered third-line options after benzodiazepine receptor agonists and ramelteon 1, 2
Mirtazapine is positioned as a third-line pharmacologic option after short-intermediate acting benzodiazepine receptor agonists and ramelteon have been considered, according to the American Academy of Sleep Medicine 3
The evidence supporting mirtazapine for chronic primary insomnia is limited in quality and generalizability, as stated by the American Academy of Sleep Medicine 1, 2

In palliative care patients with refractory insomnia, mirtazapine 7.5-30 mg at bedtime is listed as an acceptable pharmacologic option by the National Comprehensive Cancer Network 4
In patients with comorbid depression and insomnia, mirtazapine may address multiple symptoms simultaneously, as suggested by the National Comprehensive Cancer Network 4
In children with autism spectrum disorders, mirtazapine has shown effectiveness for sleep disorders, according to the American Academy of Pediatrics 5
The recommended starting dose of mirtazapine is 7.5 mg at bedtime, which can be titrated up to 15-30 mg at bedtime if needed, as stated by the American Academy of Family Physicians and the National Comprehensive Cancer Network 4, 6

The American Academy of Sleep Medicine recommends confirming chronic insomnia diagnosis and ruling out primary sleep disorders before initiating treatment with mirtazapine 1
The American Academy of Sleep Medicine suggests considering FDA-approved options first, such as benzodiazepine receptor agonists and ramelteon, before using mirtazapine as a third-line option 1, 2, 3
Mirtazapine may be considered if the patient has comorbid depression or anxiety, has failed or cannot tolerate first-line agents, or is in palliative care with refractory insomnia, as stated by the National Comprehensive Cancer Network and the American Academy of Family Physicians 4, 6

The National Comprehensive Cancer Network (NCCN) recommends that the usual dose for insomnia is 15–30 mg taken at bedtime, with higher doses up to 45 mg permissible when the medication is also being used to treat comorbid depression. 7

In palliative‑care settings for patients with refractory insomnia, NCCN lists 7.5–30 mg at bedtime as an acceptable pharmacologic option, particularly when the patient also has depression and loss of appetite. 7

NCCN advises avoiding the combination of mirtazapine with other sedating medications without careful assessment, because additive central nervous system depression can increase the risk of falls, especially in older adults. 7