Mirtazapine toxicity

Mirtazapine is a novel tetracyclic antidepressant, in overdose it frequently has a benign course with mild CNS depression and tachycardia.

Toxic Mechanism:

Centrally acting alpha-2-adrenergic antagonist that enhances the release of serotonin and noradrenaline. It is also a histamine and serotonin (5-HT2 and 5-HT3) antagonist (therefore causing drowsiness).


  • Good oral absorption
  • 85% protein bound
  • Massive volume of distribution >100L/kg
  • Hepatic metabolism, active metabolites which are renally excreted
  • Elimination half life is 20-40 hours


  • Intubation: Rarely required

Risk Assessment

  • Many patients are asymptomatic.
  • Symptoms should occur within 4 hours related to the receptors affected:
    • Mild tachycardia
    • Hypertension
    • Drowsiness (in large overdoses)
    • CNS depression is more likely if >1000 mg has been ingested but still this is rare. If the patient has significantly reduced GCS another cause should be sought.

Supportive Care

  • General measures


  • Screening: 12 lead ECG, BSL, Paracetamol level


  • Not indicated

Enhanced Elimination

  • Not clinically useful.


  • None available.


  • Patients who are asymptomatic with a normal (or baseline) 12-lead ECG and vital signs are medically cleared
  • Patients with mild sedation are managed supportively on the ward until symptoms resolve.


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Toxicology Library


Dr Neil Long BMBS FACEM FRCEM FRCPC. Emergency Physician at Kelowna hospital, British Columbia. Loves the misery of alpine climbing and working in austere environments (namely tertiary trauma centres). Supporter of FOAMed, lifelong education and trying to find that elusive peak performance.

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