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Mirtazapine (Remeron)

NaSSA • Last reviewed 2025-09-26

General information

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) indicated for the treatment of major depressive disorder in adults. It uniquely combines central presynaptic α2-autoreceptor antagonism with potent 5-HT2 and 5-HT3 antagonism, promoting serotonergic transmission while minimizing gastrointestinal and sexual side effects.

Tablets (15, 30, 45 mg) can be split; an orally disintegrating tablet (ODT) formulation supports adherence in patients who struggle with swallowing. Bedtime dosing is preferred because lower doses intensify histamine H1 antagonism and sedation.

Clinical guidelines highlight mirtazapine for patients with depression accompanied by insomnia, appetite loss, cachexia, or in those who poorly tolerate SSRIs due to nausea or sexual dysfunction. Weight gain and lipid elevations remain common and require counseling.

Caution is warranted in hepatic or renal impairment, and rare cases of severe neutropenia mandate prompt evaluation of infection symptoms.

Dosing & administration

Start 15 mg at bedtime; increase to 30 mg after 1–2 weeks if needed.

Usual effective range is 15–45 mg nightly; doses >45 mg offer limited additional benefit but may reduce sedation.

Reduce dose in moderate-to-severe renal impairment or hepatic insufficiency.

Mechanism of action

Antagonizes central presynaptic α2-adrenergic autoreceptors/heteroreceptors, increasing norepinephrine and serotonin release. Blocks 5-HT2 and 5-HT3 receptors, steering signaling toward 5-HT1A, and strongly antagonizes H1 receptors (sedation) with moderate muscarinic blockade.

Metabolism & pharmacokinetics

Rapidly absorbed with ~50% bioavailability; peak concentrations occur within 2 hours (tablet) or 1 hour (ODT). Extensive hepatic metabolism via CYP1A2, CYP2D6, and CYP3A4 produces demethylated and hydroxylated metabolites eliminated in urine (75%) and feces (15%). Elimination half-life averages 20–40 hours; steady state in ~5 days.

Drug interactions

Avoid MAOIs, linezolid, or IV methylene blue (risk of serotonin syndrome).

Additive CNS depression with alcohol, benzodiazepines, or antihistamines.

Carbamazepine and other CYP3A4 inducers may reduce levels; consider dose adjustments.

Monitoring & safety checks

Discontinuation guidance

Taper over 1–2 weeks; discontinuation symptoms are generally mild but may include irritability, insomnia, or flu-like symptoms.

References

  1. Mirtazapine Prescribing Information — DailyMed
  2. APA Clinical Practice Guideline for Depression (2023)
  3. CANMAT 2024 MDD Guidelines (2024)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.