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Tricyclic anti-depressants

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Anna Lee & Charles Gomersall

Updated June 2006


  • Generally high protein binding (85-95%)

    • pH dependent, increased by alkalosis and decreased by acidosis

  • Large volume of distribution (10-20 L/kg)

  • Elimination half life ranges from 10-20 hours

  • Anticholinergic properties of tricyclic antidepressants delayed absorption

  • CNS and CVS toxicity
    • CNS effects due to anticholinergic effects and inhibition of neural re-uptake of norepinephrine and/or serotonin
    • CVS effects due to:
      • anticholinergic effects
      • inhibition of neural re-uptake of norepinephrine and/or serotonin
      • peripheral alpha blockade
      • sodium channel blockade ⇒membrane depressant effects

Clinical features

Toxicity is expected within 6 hours after ingestion

Anticholinergic effects

"Hot as a hare, dry as a bone, red as a beet, mad as a hatter"

  • fever
  • dry skin and mucous membranes
  • lethargy, delirium, coma
  • mydriasis, blurred visiion
  • tachycardia
  • ileus
  • myoclonus
  • urinary retention

CNS toxicity

  • Confusion and coma

  • Seizure in >5% of cases

Cardiovascular toxicity

  • sinus tachycardia with QRS, QTc, PR prolongation
  • ventricular tachycardia
  • torsades des pointes (rare)
  • AV block of varying degrees
  • RBBB common
  • hypotension due to venodilation and decreases myocardial contractility


  • ECG at 4-6 h can be used to predict severity:
    • QRS <0.1 sec, no significant toxicity

    • QRS of 0.1 sec or more indicates risk of seizures
    • QRS >0.16 sec associated with ventricular arrhythmias
    • amoxapine is an exception to the rule. Status epilepticus occurs in the setting of normal QRS duration
    • absence of QRS prolongation not a sensitive predictor of low risk of toxicity
  • duration of ECG monitoring is arbitrary. Monitoring for 12h after normalization of ECG suggested


  • gastric lavage (NB tricyclics cause gastroparesis)
  • activated charcoal (but beware vomiting and aspiration). No role for multiple doses, particularly because anticholinergic induced ileus increases risk of causing intestinal obstruction
  • in severe cases and in cases with prolonged QRS aim for alkalosis (by hyperventilation and/or IV bicarbonate) to increase protein binding. Sodium bicarbonate may also have membrane stabilizing effects via a Na mechanism. Bicarbonate drug of choice for all CVS haemodynamic abnormalities
  • indications for sodium bicarbonate (dose – 1-2 mEq/kg, repeated boluses titrated to clinical effects):

    • QRS prolongation (even in the absence of acidosis)

    • malignant arrhythmia

    • hypotension

    • metabolic acidosis

  • lignocaine drug of choice for refractory ventricular arrhythmias. Anecdotal reports supporting use of phenytoin but no longer recommended. Other anti-arrhythmics contraindicated (Class IA, IC), potentially lethal (Class II), and of unproven efficacy.
  • benzodiazepines for seizures. Phenytoin for refractory cases
  • ineffective treatment includes calcium chloride, as may worsen both CVS and CNS toxicity. Physiostigmine can provoke malignant arrhythmia.

  • haemodialysis and haemoperfusion are of no benefits as the kinetic properties of TCA do not favor their elimination

Further reading

Mokhlesi B et al. Adult toxicology in critical care. Part II: specific poisonings. Chest 2003; 123:897-922

Jones A. Recent Advances in the Management of Poisoning. Therapeutic Drug Monitoring, 2002, 24:150–155

© Anna Lee & Charles Gomersall, June 2006


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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