What is the role of medications in the treatment of in pediatric tricyclic antidepressant (TCA) toxicity?

Updated: Mar 18, 2020
  • Author: Derrick Lung, MD, MPH; Chief Editor: Stephen L Thornton, MD  more...
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Answer

Pharmacologic therapy in patients with cyclic antidepressant (CA) toxicity is directed toward cardiac and central nervous system (CNS) effects of these drugs.

Cardiotoxicity

Sodium bicarbonate therapy is the cornerstone of treatment for cyclic antidepressant–induced conduction disturbances, ventricular dysrhythmias, and hypotension. The sodium load increases extracellular sodium concentration, improving the gradient across the sodium channel, and serum alkalinization to a pH of 7.45-7.55 appears to uncouple cyclic antidepressants from myocardial sodium channels.

Controlled studies have demonstrated that bicarbonate loading with an initial bolus of 1-3 mEq/kg of sodium bicarbonate is beneficial. Continuing a bicarbonate drip after the initial bolus, which is titrated to achieve a QRS width of 100 milliseconds, is widely practiced but not supported by medical evidence.

Ventricular dysrhythmias that are refractory to sodium bicarbonate may require treatment with lidocaine (class Ib), magnesium sulfate, or both. Class Ia antidysrhythmic drugs (eg, quinidine, procainamide, disopyramide) and class Ic drugs (eg, flecainide, propafenone) are contraindicated because they may worsen sodium channel inhibition.

Class III drugs (eg, amiodarone, sotalol) are contraindicated because they can further prolong the QT interval, leading to ventricular dysrhythmia. Class II beta-blockers (eg, propranolol, esmolol, metoprolol) and class IV calcium channel blockers (eg, verapamil, diltiazem, nifedipine, nicardipine) are contraindicated because they may potentiate or worsen hypotension.

Patients with hypotension refractory to fluid resuscitation and sodium bicarbonate require vasopressor support. Direct-acting alpha-agonists (eg, norepinephrine, phenylephrine) are most effective because severe hypotension is generally due to direct alpha1-blocking effects in these cases. Dopamine may not be as effective because its action is partially mediated by the release of endogenous catecholamines, and these may be depleted.

CNS toxicity

Benzodiazepines are the agents of choice for treatment of CNS toxicity from cyclic antidepressants. Phenobarbital may also be used as a long-acting anticonvulsant. Sodium bicarbonate therapy may also have benefit as the fast sodium channel blockade is thought to contribute to developement of seizures. Phenytoin and other electrolyte-channel modulating antiepileptics have traditionally been considered third-line for drug-induced seizures.

Physostigmine is an acetylcholinesterase inhibitor who use in patients with cyclic antidepressant overdoses in controversial. Although physostigmine is very effective in treating the antimuscarinic effects of the cyclic antidepressants it has no benefit for the life threatening cardiac complications.  It should only be used under direct supervision of a medical toxicologists or poison control center.

Flumazenil, a benzodiazepine antagonist, is contraindicated, even in the presence of benzodiazepine co-ingestion due to the precipitation of seizures. Several case reports describe patients with concomitant cyclic antidepressant overdoses who had seizures after the administration of flumazenil.


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