Question 3

Describe the physiological effects and principles of management of a tricyclic antidepressant overdose.

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College Answer

Good answers to this question were those that gave an accurate account of the physiological effects, e.g. inhibition of the fast sodium channels in the His-Purkinje system as well as the atrial and ventricular myocardium, decreasing conduction velocity (differential conduction inhibition of RBB being more susceptible) and increasing duration of repolarization, and the absolute refractory periods. Once having done that the rest of the answer would have flowed more easily, e.g. ECG changes and conduction disturbances. The effects of tricyclic antidepressants on Na channels and as a consequence the cardiovascular conduction abnormalities were often omitted. Anti cholinergic (e.g. slowing GIT motility) and antihistamine effects (e.g. obtundation) were often overlooked. Also frequently overlooked were basic pharmacology relevant to treatment, e.g. lipophilic, large volume of distribution, systemic acidosis reduces the extent of protein binding and increases unbound (active) drug. Additional points were available to those who not only mentioned sodium bicarbonate, but also mentioned the principles behind its use for this circumstance


Physiological effects:

Cardiovascular features
  • Tachycardia
  • Long intervals: QT, PR, QRS
  • QRS widening (>100 ms)  and right axis deviation of the terminal QRS
  • Heart block
  • Vasodilation
  • Hypotension
  • Arrhythmias, including VF and torsade

Central nervous system features

  • Drowsiness
  • Coma
  • Seizures
  • Pyramidal signs  and rigidity
  • Ophthalmoplegia

Anticholinergic features

  • Dry mouth
  • Blurred vision
  • Dilated pupils
  • Urinary retention
  • Ileus, absent bowel sounds
  • High fever, or inability to regulate temperature
  • Anhidrosis
  • Delirium

Metabolic features

  • Metabolic acidosis
  • Respiratory acidosis

Principles of management:

  • Decontamination
    • Activated charcoal
  • Enhanced elimination
    • Alkalinising the body fluids to increase drug-protein binding
  • Cardioprotection
    • Giving sodium to antagonise sodium channel blockade
    • Decreasing the binding of the TCA to the sodium channel (by alkalinising the body fluids)
  • Basic ICU supportive care (intubation, vasopressors, etc) to maintain safety in the face of sedation,  anticholinergic delirium and cardiovascular instability due to the anti-adrenergic effects


Kerr, G. W., A. C. McGuffie, and S. Wilkie. "Tricyclic antidepressant overdose: a review." Emergency Medicine Journal 18.4 (2001): 236-241.

Brown, T. C., et al. "The use of sodium bicarbonate in the treatment of tricyclic antidepressant-induced arrhythmias." Anaesthesia and intensive care 1.3 (1973): 203-210.

McCabe, James L., et al. "Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation." Annals of emergency medicine 32.3 (1998): 329-333.

Bou-Abboud, Elias, and Stanley Nattel. "Molecular mechanisms of the reversal of imipramine-induced sodium channel blockade by alkalinization in human cardiac myocytes." Cardiovascular research 38.2 (1998): 395-404.