Pharmacology · Atypical antidepressants
Mirtazapine !
An antidepressant that blocks alpha-2 receptors to release more norepinephrine and serotonin. Causes sleepiness and appetite gain; rarely, low white cells.
Updated 2026-11-01
Mechanism of action
Mirtazapine blocks presynaptic alpha-2 adrenergic autoreceptors and heteroreceptors, which normally act as a brake on release, so noradrenergic and serotonergic neurons release more transmitter. It also blocks 5-HT2 and 5-HT3 receptors, which may limit some serotonergic side effects (nausea, sexual dysfunction), and strongly blocks H1 receptors (sleepiness, appetite).
- Mirtazapine blocks presynaptic alpha-2 receptors
- The brake is removed: more norepinephrine and serotonin are released
- 5-HT2 and 5-HT3 block limits nausea and sexual side effects
- H1 block causes sleepiness and more appetite
Pharmacokinetics
- Absorption
- By mouth, as tablets or orally disintegrating tablets
- Metabolism
- Extensive in the liver
- Half-life
- About 20 to 40 hours; longer in women and older adults
Indications
- Major depressive disorder in adults
Adverse effects
Common
- Somnolence
- Increased appetite and weight gain
- Dry mouth and constipation
- Dizziness
- Rise in cholesterol and triglycerides
Contraindications
- MAO inhibitors, including linezolid and intravenous methylene blue, or within 14 days of stopping an MAOI
- Hypersensitivity to mirtazapine
Key interactions
- Alcohol, benzodiazepines and other sedatives
- Additive sedation and impaired motor skills
- MAO inhibitors and other serotonergic drugs
- Serotonin syndrome
- Drugs that prolong the QT interval
- Additive risk of arrhythmia
- Strong CYP3A inhibitors or inducers
- Higher or lower mirtazapine levels
What is monitored
- Signs of infection (fever, sore throat, mouth ulcers) with a white cell count if they appear
- Weight and lipids
- Mood and suicidal thoughts
- Sodium in older adults
Administration and safety
- Given by mouth, preferably in the evening at bedtime because of sleepiness
- Orally disintegrating tablets dissolve on the tongue
- Stopped gradually
Nursing care
- Teach the person to report fever, sore throat or mouth ulcers promptly (possible agranulocytosis)
- Track weight and appetite, and warn about drowsiness when driving
- Avoid alcohol and other sedatives
- Assess suicidal thoughts early in treatment and after dose changes
Pregnancy and breastfeeding
Long experience in pregnancy has not reliably shown a drug-related risk of major birth defects or miscarriage; untreated depression also carries risks.
Test yourself
Think of the answer, then tap the question to see it.
How does mirtazapine increase norepinephrine and serotonin release without blocking reuptake?
It blocks presynaptic alpha-2 autoreceptors and heteroreceptors, removing the negative feedback on release.
Which two side effects make mirtazapine useful for a depressed older adult with insomnia and weight loss?
Sedation and increased appetite with weight gain, mainly from H1 block.
A patient on mirtazapine has fever and sore throat. What test is needed and why?
A white cell count, because mirtazapine can rarely cause agranulocytosis; it is stopped if the count is low.
Related drugs
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MIRTAZAPINE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Mirtazapine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.