Mirtazapine Tapering Guide
mirtazapine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) approved for major depressive disorder. It has a unique mechanism that does not involve reuptake inhibition. It is known for sedation and appetite stimulation, especially at lower doses.
7.5mg, 15mg, 30mg, 45mg
Tablets: 7.5mg, 15mg, 30mg, 45mg; Orally disintegrating tablets (SolTab): 15mg, 30mg, 45mg
Category C (risk cannot be ruled out)
Mechanism of Action
Antagonist at central alpha-2 adrenergic autoreceptors and heteroreceptors, increasing noradrenergic and serotonergic neurotransmission. Also antagonizes 5-HT2A, 5-HT2C, 5-HT3, and histamine H1 receptors. The strong H1 antagonism causes sedation and weight gain.
Taper Notes
Rebound insomnia is very common at lower doses due to stronger antihistamine effect. Paradoxically more sedating at lower doses.
Hyperbolic Tapering Guidance
Tablet can be split or dissolved in water for precise dosing. Rebound insomnia at lower doses often mistaken for relapse — distinguish withdrawal from relapse by timing.
Summary written by TaperCommunity, informed by the Maudsley Deprescribing Guidelines (Horowitz & Taylor) and related literature — see Sources & References below. Not affiliated with or endorsed by the Maudsley.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated (serotonin syndrome risk)
- Serotonergic drugs increase serotonin syndrome risk
- CYP3A4 inhibitors (ketoconazole) may increase mirtazapine levels
Food Interactions
- Food has minimal effect on absorption
- Avoid alcohol (additive CNS depression)
Contraindications
- MAOIs within 14 days
- Known hypersensitivity to mirtazapine
Toxicity
Relatively low toxicity in overdose compared to TCAs. Agranulocytosis/neutropenia rarely reported. Weight gain and metabolic effects. Serotonin syndrome possible with serotonergic combinations.
Pharmacokinetics
ADME Profile
Rapidly and completely absorbed. Bioavailability ~50%. Tmax ~2 hours. Food has minimal effect on absorption.
~4.5 L/kg
Extensively metabolized hepatically via CYP2D6, CYP3A4, and CYP1A2 to demethyl and hydroxylated metabolites, which have minimal pharmacological activity.
Renal (~75%) and fecal (~15%). Less than 5% excreted unchanged in urine.
~85%
~230 mL/min (apparent oral clearance)
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Other Drug Profiles
Sources & References
Mirtazapine (mirtazapine) information on this page is sourced from peer-reviewed research, regulatory bodies, clinical guidelines, and patient-advocacy organizations.
Encyclopedic & chemical databases
Neutral, high-authority entity references.
Peer-reviewed research
Primary literature cited in this taper guide.
- Horowitz MA, Taylor D 2019 — Tapering of SSRI treatment to mitigate withdrawal symptoms (hyperbolic taper) (The Lancet Psychiatry)
- Davies J, Read J 2019 — A systematic review into the incidence, severity and duration of antidepressant withdrawal effects (Addictive Behaviors)
- Framer A 2021 — The patient voice: an exploration of the experience of withdrawal from antidepressants (Therapeutic Advances in Psychopharmacology)
Clinical guidelines
Evidence-based deprescribing and prescribing standards.
Deprescribing-specific resources
Clinician-facing references on tapering protocols.
- Deprescribing.org — Evidence-based deprescribing algorithms from the Bruyère Research Institute
- Royal College of Psychiatrists — Stopping antidepressants — UK clinical guidance on safely discontinuing antidepressants
Patient-advocacy & lived-experience
Long-running communities documenting withdrawal experience.
- Surviving Antidepressants — tapering forum — Long-running community archive of antidepressant taper experiences
- Inner Compass Initiative — Withdrawal Project — Peer-led resources for psychiatric drug withdrawal
- Mad in America — antidepressant withdrawal archive — Journalism and personal narratives on SSRI/SNRI discontinuation
- RxISK — adverse drug reaction reporting — Independent database of patient-reported adverse effects
TaperCommunity does not provide medical advice. Always consult a qualified prescriber before adjusting psychiatric medication.