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).

Toxicokinetics: 

• 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

Resuscitation:

• 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

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level

Decontamination:

• Not indicated

Enhanced Elimination

• Not clinically useful.

Antidote

• None available.

Disposition

• 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.

References:

• Berling I, Isbister GK. Mirtazapine overdose is unlikely to cause major toxicity. Clinical Toxicology 2014; 52:20-24