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Antidepressant Toxicity Medication

  • Author: Jeena Jacob, MD, PharmD; Chief Editor: Asim Tarabar, MD  more...
Updated: Apr 12, 2015

Medication Summary

The mainstay of specific treatment of significant TCA-related toxicity is NaHCO3 administered in conjunction with supportive care, including aggressive airway support, antiseizure, vasopressor, and dysrhythmic medications. Indications for NaHCO3 administration include QRS widening, hypotension, dysrhythmias, and seizures that are associated with QRS widening. NaHCO3 replaces lidocaine as the drug of choice for ventricular tachycardia following TCA overdose in a variation of the usual ACLS guidelines. Hypotension with evidence of shock not responsive to judicious fluid therapy and sodium bicarbonate are indications for pressors.

Contraindicated medications include beta-blockers, calcium channel blockers, and class IA (procainamide, quinidine, disopyramide, moricizine), class IC (flecainide, propafenone), and possibly class III (bretylium, amiodarone, sotalol) antidysrhythmics.


GI decontaminant

Class Summary

Activated charcoal is not routinely indicated. In cases of altered mental status, the benefits of charcoal need to be weighed against the risk of aspiration. Therefore, prior to charcoal administration, the airway needs to be secured in patients with an altered mental status. Since the anticholinergic effects of TCAs delay gastric emptying and slow GI motility, this may allow efficacy for charcoal when administered relatively late postingestion.

Activated charcoal (Liqui-Char)


Binds TCAs, limiting absorption. Clinical benefit has not been demonstrated clearly.


Cardiovascular agents

Class Summary

Serum alkalinization with NaHCO3 is the first-line and most effective therapy for arrhythmias. Vasopressors can be useful in correcting hypotension. Lidocaine is the second-line agent behind alkalinization for arrhythmias. Class IA and IC antiarrhythmic agents (eg, procainamide, disopyramide, quinidine, flecainide, encainide) are contraindicated, as are beta-blockers and calcium channel blockers.

Sodium bicarbonate (Neut)


First-line drug for cardiovascular morbidity in TCA poisoning. Provides exogenous sodium to overcome the competitive fast sodium channel blockade produced by TCA, and produces an alkalemia (or reverses acidemia) that mitigates the fast sodium channel blockade by TCA.

Indicated for QRS widening, dysrhythmias, hypotension, and seizures that are associated with QRS widening. Patient can be monitored and given boluses of bicarbonate prn if QRS widening and block resolves with initial treatment. Maintain serum potassium levels (see Precautions below). Resolution of QRS widening is a reasonable endpoint for NaHCO3 administration. However, because it may recur, patients who have had QRS widening need to be on a cardiac monitor that is being continuously monitored.

Norepinephrine (Levophed)


Other vasopressors may also be used. Norepinephrine's vasopressive effect is from its alpha alpha-adrenergic agonist properties. Vasopressors are indicated for persistent hypotension not responsive to judicious fluid loading and sodium bicarbonate.

Epinephrine (Adrenaline)


Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypertension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.

Phenylephrine (Neo-Synephrine)


Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. Increases peripheral venous return. Generally not used as a first-line agent. Correct volume deficits before administration.

Lidocaine (Xylocaine)


Secondary to NaHCO3 for dysrhythmias due to TCA toxicity. Class IB antiarrhythmic that increases electrical stimulation threshold of the ventricle, suppressing automaticity of conduction through the tissue. Second-line agent for treatment of ventricular dysrhythmias.



Class Summary

Most seizures are short, self-limited, and may resolve before treatment can be administered; however, if prolonged greater than several minutes or repetitive, treatment is indicated. Controversy exists about the indications for sodium bicarbonate with seizures. A trial of NaHCO3 is recommended for seizures that are associated with QRS widening, after benzodiazepine treatment. If seizures are refractory to all treatment, paralysis is indicated to stop motor activity and resultant metabolic acidosis. Benzodiazepines may calm a patient presenting with agitation secondary to the anticholinergic effects. However, their use may exacerbate CNS depression from TCA overdose, so their use for this indication must be accompanied by aggressive monitoring and management of the airway.

Lorazepam (Ativan)


Increasing the action of GABA, a major inhibitory neurotransmitter, may depress all levels of CNS, including limbic and reticular formation.

Diazepam (Valium)


Depresses all levels of CNS (eg, limbic and reticular formation) by increasing activity of GABA.

Phenobarbital (Barbita, Luminal)


Not used often because of the preferable safety profile of benzodiazepines but an effective antiseizure medication.

Contributor Information and Disclosures

Jeena Jacob, MD, PharmD Associate Director, Medical Toxicology Fellowship, North Shore University Hospital; Assistant Professor of Emergency Medicine, Hofstra North Shore-LIJ School of Medicine

Jeena Jacob, MD, PharmD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.


Theodore I Benzer, MD, PhD Assistant Professor in Medicine, Harvard Medical School; Director of the ED Observation Unit, Director of Toxicology, Chair of Quality and Safety, Department of Emergency Medicine, Massachusetts General Hospital

Theodore I Benzer, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

David C Lee, MD Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Eric Legome, MD, and Craig Smollin, MD, to the development and writing of this article.

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Toxicity, antidepressant. ECG shows the terminal R wave in aVR and the widened QRS complex associated with tricyclic antidepressant (TCA) toxicity.
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