How should I taper off Mirtazapine (mirtazapine)?

Rebound insomnia is very common at lower doses due to stronger antihistamine effect. Paradoxically more sedating at lower doses. 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.

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Mirtazapine Tapering Guide

mirtazapine

NaSSAFDA 1996

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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.

Common Doses

7.5mg, 15mg, 30mg, 45mg

Formulations

Tablets: 7.5mg, 15mg, 30mg, 45mg; Orally disintegrating tablets (SolTab): 15mg, 30mg, 45mg

Pregnancy

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.

Maudsley Deprescribing 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.

Common Withdrawal Symptoms

rebound insomniaanxietynauseaheadacheirritabilityappetite changes

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.

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.

Wikipedia entry for mirtazapine

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.

Pharmacokinetics

ADME Profile

Absorption

Rapidly and completely absorbed. Bioavailability ~50%. Tmax ~2 hours. Food has minimal effect on absorption.

Distribution

~4.5 L/kg

Metabolism

Extensively metabolized hepatically via CYP2D6, CYP3A4, and CYP1A2 to demethyl and hydroxylated metabolites, which have minimal pharmacological activity.

Elimination

Renal (~75%) and fecal (~15%). Less than 5% excreted unchanged in urine.

Protein Binding

~85%

Clearance

~230 mL/min (apparent oral clearance)

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