Mirtazapine (for sleep)
Noradrenergic and specific serotonergic antidepressant (NaSSA) used off-label at low doses (7.5-15 mg) as a sedating sleep aid. Strongly promotes sleep continuity via H1 blockade, but reliably causes weight gain, increased appetite, and next-day sedation, with the paradox that sedation is strongest at the lowest doses.
01 Overview
Mirtazapine (brand Remeron) is an antidepressant approved at 15-45 mg, but low doses (7.5-15 mg) are widely used off-label for insomnia, particularly in patients with comorbid depression, anxiety, poor appetite, or weight loss. It is non-scheduled and not habit-forming.
A pharmacological quirk defines its use: at low doses its potent H1 antihistamine sedation dominates, so 7.5 mg is often more sedating than 30 mg, at which noradrenergic activation partly offsets the antihistamine effect. It reliably improves sleep continuity, but appetite stimulation and weight gain are near-universal and often the deciding factor against it, along with next-day grogginess.
02 Mechanism
Antagonises central alpha-2 adrenergic autoreceptors (boosting noradrenaline and serotonin release) plus 5-HT2/5-HT3 and potent histamine H1 receptors; H1 blockade drives the sedative and appetite-stimulating effects, strongest at low doses.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Sleep (off-label) | 7.5–15 mg/day | Oral | 7.5-15 mg at bedtime; sedation is paradoxically strongest at the lowest doses. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved sleep continuityReduces sleep onset latency and awakenings; increases slow-wave sleep. | Clinical | ||
| Appetite stimulationIncreases appetite — beneficial in cachexia or poor intake, unwanted otherwise. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Restless legs / vivid dreamsSome users develop restless-legs symptoms or unusually vivid dreams. | Mild | Uncommon | Observational | |
| Weight gain / increased appetiteMarked appetite increase and weight gain, often several kilograms. | Moderate | Very common | Clinical | |
| Next-day sedationProlonged drowsiness driven by the long half-life; paradoxically worse at low doses. | Moderate | Common | Clinical |