BSN Tracker

mirtazapine

Brand: Remeron, Remeron SolTab

⚠ BBW Beers Criteria Prototype Drug
Drug Class: noradrenergic and specific serotonergic antidepressant (NaSSA)
Drug Family: antidepressant
Subclass: alpha-2 antagonist antidepressant
Organ Systems: cns

Mechanism of Action

Blocks presynaptic alpha-2 autoreceptors and heteroreceptors, disinhibiting norepinephrine and serotonin release. Simultaneously blocks 5-HT2A, 5-HT2C, and 5-HT3 receptors, channeling serotonin's effects through 5-HT1A pathways and reducing nausea/sexual side effects. Potent H1 blockade contributes to sedation and appetite stimulation.

alpha-2 adrenergic receptor5-HT2A receptor5-HT2C receptor5-HT3 receptorH1 histamine receptor

Indications

  • major depressive disorder
  • off-label: nausea
  • off-label: insomnia
  • off-label: weight gain in cancer/HIV cachexia
  • off-label: PTSD

Contraindications

  • concurrent MAOI use

Adverse Effects

Common

  • sedation
  • increased appetite
  • weight gain
  • dry mouth
  • constipation
  • dizziness

Serious

  • agranulocytosis (rare)
  • serotonin syndrome
  • suicidal ideation
  • hyponatremia

Pharmacokinetics (ADME)

Absorption well absorbed orally; bioavailability ~50% due to first-pass; food has no significant effect
Distribution protein binding ~85%; Vd ~4.5 L/kg
Metabolism hepatic via CYP1A2, CYP2D6, and CYP3A4; active metabolite demethylmirtazapine
Excretion renal (~75%) and fecal (~15%); dose reduction in severe renal/hepatic impairment
Half-life 20-40 hours
Onset 1-3 weeks
Peak 2 hours
Duration 24 hours
Protein Binding 85%
Vd 4.5 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs serotonin syndrome contraindicated
alcohol/CNS depressants additive CNS depression due to H1 blockade and sedation major
benzodiazepines additive sedation and psychomotor impairment moderate

Nursing Considerations

  1. Sedation is dose-dependent and paradoxically more pronounced at lower doses (15 mg > 30 mg) due to H1:alpha-2 receptor blockade ratio; counsel patients about drowsiness, especially when initiating.
  2. Weight gain and increased appetite are common and clinically meaningful — monitor BMI monthly; mirtazapine is sometimes intentionally chosen in patients with depression plus undernutrition or cancer cachexia.
  3. Although agranulocytosis is rare (<1 per 1000 patients), instruct patients to report fever, sore throat, or mouth sores immediately; obtain CBC if infection signs occur.
  4. Mirtazapine lacks significant CYP inhibition and causes no sexual dysfunction, making it advantageous in patients with SSRI-induced sexual side effects or in men with erectile dysfunction.

Clinical Pearls

  • The 'paradox of mirtazapine' refers to its more pronounced sedation at 7.5-15 mg than at 30-45 mg; as the dose increases, noradrenergic activation offsets H1-mediated sedation.
  • Mirtazapine is the only antidepressant that reliably stimulates appetite and promotes weight gain, making it valuable in depressed patients with cancer, AIDS, or chemotherapy-induced anorexia.

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Major Depressive Disorder Noradrenergic And Specific Serotonergic Antidepressant (NaSSA) Off-label: Insomnia Off-label: Nausea Off-label: PTSD Off-label: Weight Gain In Cancer/HIV Cachexia
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