Mirtazapine
Mirtazapine is an atypical antidepressant of the NaSSA class (noradrenergic and specific serotonergic antidepressant). It is sedating and appetite-stimulating at low doses, with notably fewer sexual side effects than SSRIs, and is widely used in depression with insomnia, weight loss or anxiety.
- Chemical formula
- C17H19N3
- CAS number
- 85650-52-8
- ATC code
- N06AX11
- Molecular weight
- 265.36 g/mol
- Drug class
- Atypical antidepressant (NaSSA)
- Also known as
- Remeron, Zispin, Avanza
What is it?
Mirtazapine is an atypical antidepressant of the NaSSA class (noradrenergic and specific serotonergic antidepressant) approved by the FDA in 1996, marketed as Remeron by Organon (now Merck) and as Zispin in the UK and Avanza in Australia. Authorised generic mirtazapine has been widely available since 2004. It has a distinctive profile — sedating, appetite-stimulating, low sexual side effects — that makes it especially useful in older or thin depressed patients with insomnia.
Mechanism of action
Mirtazapine antagonises presynaptic α2-adrenergic autoreceptors and heteroreceptors, increasing noradrenaline and serotonin release. It also blocks postsynaptic 5-HT2A, 5-HT2C and 5-HT3 receptors, which redirects increased serotonin onto 5-HT1A receptors. It is a potent H1 histamine receptor antagonist, which explains the strong sedative and appetite-stimulating effects, particularly at low doses. Therapeutic antidepressant effect builds over 4–6 weeks.
Pharmacokinetics
Mirtazapine is well absorbed after oral administration with peak plasma at ~2 hours. The terminal half-life is 20–40 hours, supporting once-daily dosing, usually at bedtime. Hepatic metabolism is via CYP2D6, CYP3A4 and CYP1A2 with active metabolites contributing little to clinical effect. Hepatic or renal impairment substantially prolongs half-life and may require dose adjustment.
Indications
Mirtazapine is approved for major depressive disorder. It is widely used off-label for depression with insomnia, depression in elderly patients with poor appetite, depression in patients intolerant of SSRI sexual side effects, and as adjunctive sleep agent in psychiatric practice. According to clinical guidelines, mirtazapine is often considered second-line in major depression but is first-line where its sedating, appetite-stimulating profile aligns with the patient's symptoms.
Safety profile
Common adverse effects include sedation (highest at low doses 7.5–15mg, paradoxically less at higher doses), increased appetite, weight gain, dry mouth and dizziness. Sexual dysfunction is uncommon compared with SSRIs. Rare effects include agranulocytosis (very rare, requires immediate review of unexplained sore throat or fever) and elevated lipids. According to the prescribing information, paradoxical activation can occur and discontinuation should be tapered to avoid mild withdrawal symptoms.
Products containing this ingredient
Frequently asked questions
Why is low-dose mirtazapine more sedating than higher dose? ▾
At low doses (7.5–15mg), the antihistamine (H1) effect dominates, producing strong sedation. At higher doses, increased noradrenergic transmission counteracts the antihistamine sedation, so 30mg or 45mg is often less sleepy than 15mg. According to clinical practice, this is exploited by using 15mg for insomnia plus depression and titrating up only if depression does not respond.
Is mirtazapine better tolerated than SSRIs? ▾
Mirtazapine causes notably less sexual dysfunction and gastrointestinal upset than SSRIs but causes more sedation, weight gain and drowsiness. According to current guidelines, the trade-offs make it a preferred second-line agent in patients intolerant of SSRI side effects, particularly when the symptom profile (insomnia, weight loss, low appetite) aligns with mirtazapine's strengths.
Does mirtazapine cause withdrawal on stopping? ▾
Mirtazapine has a moderate half-life (20–40 hours) and most users can stop with limited or no discontinuation symptoms. According to the prescribing information, gradual tapering over 1–2 weeks is recommended where possible. Symptoms when they occur include dizziness, nausea, irritability and disturbed sleep, and resolve within days.
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