eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Tricyclic Antidepressant: Differential Diagnoses & Workup

Author: Samara Soghoian, MD, MA, Clinical Assistant Professor of Emergency Medicine, New York University School of Medicine, Bellevue Hospital Center
Coauthor(s): Christopher I Doty, MD, FACEP, FAAEM, Assistant Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center; Frank A Maffei, MD, FAAP, Associate Professor of Pediatrics, Temple University School of Medicine; Director of Medical Student Affairs, Geisinger Health System; Pediatric Critical Care Attending Physician, Janet Weis Children's Hospital at Geisinger Medical Center; Heidi Connolly, MD, Associate Professor of Pediatrics and Psychiatry, University of Rochester; Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center
Contributor Information and Disclosures

Updated: Oct 22, 2009

Differential Diagnoses

Acidosis, Metabolic
Toxicity, Calcium Channel Blocker
Adrenal Insufficiency
Toxicity, Carbamazepine
Atrioventricular Block, Second Degree
Toxicity, Deadly in a Single Dose
Atrioventricular Block, Third Degree, Acquired
Toxicity, Digitalis
Bundle Branch Block, Left
Toxicity, Ethanol
Bundle Branch Block, Right
Toxicity, Hallucinogens - LSD
Diabetic Ketoacidosis
Toxicity, Hallucinogens - PCP
Long QT Syndrome
Toxicity, Iron
Myocardial Infarction in Childhood
Toxicity, Isoniazid
Myocarditis, Nonviral
Toxicity, Mushrooms - Muscarine
Myocarditis, Viral
Toxicity, Salicylate
Neuroleptic Malignant Syndrome
Toxicity, Tricyclic Antidepressant
Respiratory Distress Syndrome
Ventricular Fibrillation
Respiratory Failure
Ventricular Tachycardia
Sepsis
Status Epilepticus
Substance Abuse: Cocaine

Other Problems to Be Considered

Toxicity, Anticholinergic
Toxicity, Antihistamine
Toxicity, Antidysrhythmic
Toxicity, Clonidine
Toxicity, Cocaine
Toxicity, Monoamine Oxidase Inhibitor
Toxicity, Neuroleptic Agents
Toxicity, Phencyclidine
Cyclobenzaprine toxicity
Serotonin syndrome

Workup

Laboratory Studies

The following studies are indicated in cyclic antidepressant (CA) poisoning:

  • Routine monitoring: CBC count, electrolyte levels (with determination of anion gap), urinalysis (UA), and urinary chorionic gonadotropin (UCG) levels should be routinely monitored in all patients with potential overdose.
  • ABG: An arterial or venous blood sample should be sent to assess plasma pH. Cyclic antidepressant toxicity usually results in mixed acidosis due to respiratory depression coupled with hypotension caused by both myocardial depression and peripheral vasodilation, thus resulting in increased lactate production. Acidemia decreases protein binding and increases plasma levels of free drug. Therefore, correction of serum pH is a primary target of therapy in cyclic antidepressant overdose.
  • Serum potassium level: Hypokalemia frequently occurs because of increased stimulation of catecholamine receptors due to blockage of norepinephrine reuptake. In one series, 9% of patients with tricyclic antidepressant (TCA) overdose had serum potassium levels of less than 3.
  • Renal function tests: Cyclic antidepressant metabolites are excreted by the kidneys after hepatic metabolism by the cytochrome P450 system. Some of these metabolites are pharmacologically active, and impaired renal function may prolong or exacerbate toxicity.
  • Toxicology screen: Because of the ubiquity of cyclic antidepressants and the lack of acute symptoms associated with cyclic antidepressant toxicity, serum acetaminophen levels should be routinely checked. A urine toxicology screen and screening for other potential co-ingestants (eg, ethanol, acetylsalicylic acid [ASA]) may be performed if indicated based on the clinical picture.
  • Serum cyclic antidepressant level
    • Serum cyclic antidepressant levels are not readily available and not likely to be helpful in the immediate treatment of the patient with cyclic antidepressant poisoning. levels may be used to confirm suspected poisoning or give a rough estimate of overdose. However, levels do not correlate with toxic effects. This is due to the highly lipophilic nature of cyclic antidepressants and high degree of protein binding. A large volume of distribution means that tissue levels of cyclic antidepressant are often much higher than serum levels of free drug.
    • A recent meta-analysis of prognostic indicators to predict seizures, arrhythmias, and death in cyclic antidepressant overdose pooled data from 18 studies and found that the sensitivity and specificity of serum cyclic antidepressant concentration to predict ventricular arrhythmias were 0.78 (95% confidence interval [CI], 0.56-0.9) and 0.57 (95% CI, 0.46-0.67), respectively.7 The sensitivity and specificity of cyclic antidepressant concentration to predict death were 0.76 (95% CI, 0.49-0.91) and 0.6 (95% CI, 0.47-0.72), respectively.

Imaging Studies

  • Chest radiography should be performed if a history or suspicion of aspiration is noted or to rule out other causes of fever, hypotension, or respiratory failure.
  • Neuroimaging should also be considered for patients with altered mental status, especially if the history is unclear or if trauma is a potential comorbid contributor.

Other Tests

  • ECG is useful as both a screening tool for cyclic antidepressant exposure and as a prognostic indicator in cyclic antidepressant poisoning.8

    Toxicity, antidepressant. ECG shows the terminal ...

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

    [ CLOSE WINDOW ]
    Toxicity, antidepressant. ECG shows the terminal ...

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

  • The most common ECG finding in cyclic antidepressant poisoning is sinus tachycardia, usually due to peripheral anticholinergic effects. Other ECG changes that should be sought include prolongation of the PR, QRS, and QT intervals; atrioventricular (AV) blocks; ventricular ectopy; nonspecific ST-T changes; terminal 40-millisecond right-axis deviation of the QRS in the frontal plane; and the Brugada pattern, including right bundle branch block (RBBB) and a downsloping ST segment elevation in leads V1 -V3.
  • Cyclic antidepressants block fast sodium channels in the myocardium and slow phase zero depolarization of the action potential. Ventricular depolarization is delayed, which leads to a prolonged QRS interval. QRS interval is evaluated best using the limb leads. Widening of the QRS complex is associated with the development of seizures and arrhythmias, and QRS duration in the limb leads can be used to assess the severity of cyclic antidepressant toxicity. Patients with a QRS of less than 100 milliseconds are unlikely to develop seizures and arrhythmias. When the QRS is more than 100 milliseconds, patients have a 34% chance of seizure and a 14% chance of serious arrhythmia. QRS complexes of more than 160 milliseconds have a 50% chance of developing ventricular arrhythmias.
  • Cyclic antidepressants affect the right fascicle of the heart. The reason is unknown, but the effect can be observed as an exaggerated height of the R wave in lead aVR. A large R wave in lead aVR is a highly sensitive screening tool for cyclic antidepressant exposure. In addition, the amplitude of this R wave has been associated with increased risk of toxic effects. Data suggest that the finding of a large R wave in lead aVR may be even more predictive of seizure and arrhythmia than prolongation of the QRS complex. Liebelt et al found that an R wave of more than 3 mm in lead aVR was 81% sensitive and 73% specific for the development of seizures and arrhythmias.9

Procedures

  • Gastric lavage: This may be indicated in cases in which a potentially significant ingestion is known to have occurred within 1 hour of presentation. In a study of 592 patients with TCA poisoning, Kulig et al showed that gastric lavage improved clinical outcome only when performed within 1 hour of ingestion.10 No evidence suggests that gastric lavage reduces morbidity and mortality if instituted outside of this time frame.
  • Tracheal intubation
    • Clinical deterioration of symptomatic patients should be anticipated, and early intubation should be considered in these patients.
    • Patients should be intubated prior to gastric lavage.
    • Patients who are obtunded or comatose should be intubated for airway protection.
    • Elective intubation should be considered for symptomatic patients with poor cardiopulmonary reserve who may not be able to tolerate large fluid loads induced by fluid and sodium bicarbonate therapy. Early intubation with mild hyperventilation may be used to help alkalinize the serum in these patients.

More on Toxicity, Tricyclic Antidepressant

Overview: Toxicity, Tricyclic Antidepressant
Differential Diagnoses & Workup: Toxicity, Tricyclic Antidepressant
Treatment & Medication: Toxicity, Tricyclic Antidepressant
Follow-up: Toxicity, Tricyclic Antidepressant
Multimedia: Toxicity, Tricyclic Antidepressant
References
[ CLOSE WINDOW ]

References

  1. Watson WA, Litovitz TL, Rodgers GC Jr, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2005;23(5):589-666. [Medline].

  2. Alonso A, Garcia Rodriguez LA, Logroscino G, et al. Use of antidepressants and the risk of Parkinson's disease: a prospective study. J Neurol Neurosurg Psychiatry. 2009;80:671-675. [Medline].

  3. D'Agostino ML, Risser J, Robinson-Bostom L. Imipramine-induced hyperpigmentation: a case report and review of the literature. Journal of Cutaneous Pathology. 2008;36:799-803. [Medline].

  4. Rosenberg LB, Whang W, Shimbo D, et al. Exposure to tricyclic antidepressants is associated with an increased risk of incident CHD events in a population-based study. International Journal of Cardiology. 2009;epub ahead of print:[Medline].

  5. Kwadijk-de Gijsel S, Bijl MJ, Visser LE, et al. Variation in the CYP2D6 gene is associated with a lower serum sodium concentration in patients on antidepressants. British Journal of Clinical Pharmacology. 2009;68:221-225. [Medline].

  6. Lester L, McLaughlin S. SALT: a case for the sodium channel blockade toxidrome and the mnemonic SALT. Ann Emerg Med. Feb 2008;51(2):214. [Medline].

  7. Bailey B, Buckley NA, Amre DK. A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose. J Toxicol Clin Toxicol. 2004;42(6):877-88. [Medline].

  8. Liebelt EL, Ulrich A, Francis PD, Woolf A. Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med. Oct 1997;25(10):1721-6. [Medline].

  9. Liebelt EL, Francis PD, Woolf AD. ECG lead aVR versus QRS interval in predicting seizures and arrhythmias in acute tricyclic antidepressant toxicity. Ann Emerg Med. Aug 1995;26(2):195-201. [Medline].

  10. Kulig K, Bar-Or D, Cantrill SV, Rosen P, Rumack BH. Management of acutely poisoned patients without gastric emptying. Ann Emerg Med. Jun 1985;14(6):562-7. [Medline].

  11. Heard K, Dart RC, Bogdan G, et al. A preliminary study of tricyclic antidepressant (TCA) ovine FAB for TCA toxicity. Clin Toxicol (Phila). 2006;44(3):275-81. [Medline].

  12. Banks CJ, Furyk JS. Review article: Hypertonic saline use in the emergency department. Emerg Med Australas. May 6 2008;[Medline].

  13. Algren DA, Sutter ME. Treatment of tricyclic antidepressant cardiac toxicity. Pediatr Emerg Care. Mar 2008;24(3):199. [Medline].

  14. Boehnert MT, Lovejoy FH Jr. Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants. N Engl J Med. Aug 22 1985;313(8):474-9. [Medline].

  15. Callaham M, Kassel D. Epidemiology of fatal tricyclic antidepressant ingestion: implications for management. Ann Emerg Med. Jan 1985;14(1):1-9. [Medline].

  16. Chyka PA, Seger D. Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1997;35(7):721-41. [Medline].

  17. Ellenhorn MJ. Ellenhorn's Medical Toxicology. 2nd ed. Baltimore, MD: Williams & Wilkins; 1997:624-36.

  18. Farrar HC, James LP. Characteristics of pediatric admissions for cyclic antidepressant poisoning. Am J Emerg Med. Sep 1999;17(5):495-6. [Medline].

  19. Weisman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank's Toxicologic Emergencies. 6th ed. McGraw-Hill Professional; 1998:925-33.

  20. Goodwin DA, Lally KP, Null DM Jr. Extracorporeal membrane oxygenation support for cardiac dysfunction from tricyclic antidepressant overdose. Crit Care Med. Apr 1993;21(4):625-7. [Medline].

  21. James LP, Kearns GL. Cyclic antidepressant toxicity in children and adolescents. J Clin Pharmacol. Apr 1995;35(4):343-50. [Medline].

  22. Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. Jul 2001;18(4):236-41. [Medline].

  23. Liebelt EL, DeAngelis CD. Evolving trends and treatment advances in pediatric poisoning. JAMA. Sep 22-29 1999;282(12):1113-5. [Medline].

  24. Liebelt EL, Shanon M. Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: the pivotal role for alkalinization and sodium loading. Pediatr Emerg Care. Aug 1998;14(4):293-8. [Medline].

  25. Newton EH, Shih RD, Hoffman RS. Cyclic antidepressant overdose: a review of current management strategies. Am J Emerg Med. May 1994;12(3):376-9. [Medline].

  26. Pentel PR, Keyler DE. Clinical Management of Poisoning and Drug Overdose. 3rd ed. Philadelphia, PA: WB Saunders Co; 1998:437-49.

  27. Pimentel L, Trommer L. Cyclic antidepressant overdoses. A review. Emerg Med Clin North Am. May 1994;12(2):533-47. [Medline].

  28. Reith D, Fountain J, Tilyard M, McDowell R. Antidepressant poisoning deaths in New Zealand for 2001. N Z Med J. Oct 24 2003;116(1184):U646. [Medline].

  29. Teba L, Schiebel F, Dedhia HV, Lazzell VA. Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressant overdose. Am J Emerg Med. Nov 1988;6(6):566-8. [Medline].

  30. Tenenbein M. Position statement: whole bowel irrigation. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1997;35(7):753-62. [Medline].

  31. Vale JA. Position statement: gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol. 1997;35(7):711-9. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

cyclic antidepressant, cyclic antidepressant toxicity, CA toxicity, CA overdose, CA poisoning, CA, tricyclic antidepressant toxicity, TCA, TCA overdose, TCA toxicity, TCA poisoning, antidepressant overdose, antidepressant toxicity, antidepressant poisoning

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Samara Soghoian, MD, MA, Clinical Assistant Professor of Emergency Medicine, New York University School of Medicine, Bellevue Hospital Center
Samara Soghoian, MD, MA is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Christopher I Doty, MD, FACEP, FAAEM, Assistant Professor of Emergency Medicine, Residency Program Director, Department of Emergency Medicine, Kings County Hospital Center, State University of New York Downstate Medical Center
Christopher I Doty, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Frank A Maffei, MD, FAAP, Associate Professor of Pediatrics, Temple University School of Medicine; Director of Medical Student Affairs, Geisinger Health System; Pediatric Critical Care Attending Physician, Janet Weis Children's Hospital at Geisinger Medical Center
Frank A Maffei, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Heidi Connolly, MD, Associate Professor of Pediatrics and Psychiatry, University of Rochester; Director, Pediatric Sleep Medicine Services, Strong Sleep Disorders Center
Heidi Connolly, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Medical Editor

Michael E Mullins, MD, Assistant Professor, Department of Emergency Medicine, Washington University School of Medicine
Michael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Emergency Physicians
Disclosure: Johnson & Johnson stock ownership None; Savient Pharmaceuticals stock ownership None

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
Jeffrey R Tucker, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, and Massachusetts Medical Society
Disclosure: Merck Salary Employment

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD, Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin
Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.