Atypical antidepressants · Psychiatry
Mirtazapine
Remeron®(brand names vary by market)
Sedation and appetite as the point, not the side effect.
Mechanism
Blocks presynaptic alpha-2 autoreceptors, increasing noradrenaline and serotonin release, while antagonising 5-HT2, 5-HT3 and H1 receptors: fewer serotonergic side effects, more sedation and appetite.
Indications
- Major depressive disorder, particularly with insomnia or weight loss
Formulations
Dosing concepts
The inverted dose relationship
Lower doses are MORE sedating: the antihistamine effect saturates early while noradrenergic activation keeps rising. Increasing the dose to help sleep is exactly backwards.
Timing
Given at night, so the sedation lands where it is wanted.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~50%
- Half-life
- 20 to 40 h
- Elimination
- hepatic: CYP1A2, 2D6 and 3A4; few clinically important interactions
- Protein binding
- ~85%
Adverse effects
- SedationcommonThe reason it is chosen, and the reason it is stopped, depending on the patient.
- Increased appetite and weight gaincommon
- Dry mouthcommon
- AgranulocytosisseriousRare; fever and sore throat warrant a white count.
- Hyponatremiaserious
Contraindications & precautions
Contraindications
- Concurrent or recent MAO inhibitor
Precautions
- Obesity or metabolic syndrome
- Older adults, where sedation means falls
- Bipolar disorder
Interactions
Monitoring
Mood and sleep
Both endpoints
Weight
Gain can be substantial and is sometimes the goal
Full blood count if fever or sore throat
Rare agranulocytosis
Counselling points
- Take it at bedtime.
- It will make you drowsy and hungry, especially at first. In your case that may be part of the point.
- Do not drive until you know how it affects you the next morning.
- Tell us about fever or a sore throat.
Clinical pearls
- In a frail depressed older adult who is not sleeping and is losing weight, mirtazapine's two most complained-about effects are the treatment. Matching the drug's personality to the patient's problem is the whole art here.
- It has minimal sexual dysfunction and can be used to rescue a patient who abandoned an SSRI for that reason.
References & review
- Mirtazapine product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.