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Toxicity, Cyclic Antidepressants: Differential Diagnoses & Workup

Author: Vivian Tsai, MD, MPH, Assistant Professor at Mount Sinai School of Medicine, Queens Hospital Center
Coauthor(s): Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate at Brooklyn; Mark Biittner, MD, Consulting Staff, Department of Emergency Medicine, Sutter Roseville Medical Center; Daniel M Joyce, MD, Consulting Staff, Department of Emergency Medicine, Saint Vincent's and Saint Mary's Medical
Contributor Information and Disclosures

Updated: Nov 3, 2009

Differential Diagnoses

Encephalitis
Sinus Bradycardia
Heart Block, First Degree
Status Epilepticus
Heart Block, Second Degree
Torsade de Pointes
Heart Block, Third Degree
Toxicity, Antidepressant
Heat Exhaustion and Heatstroke
Toxicity, Antihistamine
Hyperkalemia
Toxicity, Digitalis
Hypocalcemia
Toxicity, Isoniazid
Hyponatremia
Toxicity, Local Anesthetics
Metabolic Acidosis
Toxicity, MDMA
Pediatrics, Child Abuse
Toxicity, Salicylate
Pediatrics, Febrile Seizures
Ventricular Fibrillation
Pediatrics, Status Epilepticus
Ventricular Tachycardia
Plant Poisoning, Alkaloids - Isoquinoline and Quinoline
Withdrawal Syndromes
Plant Poisoning, Glycosides - Cardiac
Wolff-Parkinson-White Syndrome

Other Problems to Be Considered

Brugada syndrome

Workup

Laboratory Studies

  • Studies have shown that serum cyclic antidepressant (CA) level does not correlate well with severity of CA toxicity and is a poor predictor of clinical outcome.
  • Because multisubstance ingestion is common, routine screening for other potentially treatable toxins is recommended (eg, acetaminophen). Request for the other serum toxicologic levels should be guided based on the clinical picture. For example, in patients with acidosis, assess for aspirin, ethylene glycol, and methanol.
  • Assess the following:
    • Electrolyte, BUN, and creatinine levels
    • Anion gap
    • CBC count
    • Alcohol level
    • ABGs for evaluation of acidosis or hypoxia
  • Point-of-care qualitative urine immunoassays are available. They detect the presence of CA in the body. Test results are positive for most TCAs in the subtherapeutic-to-toxic range, with the exception of clomipramine. False-positive results due to cross-reactivity occur in patients who are also taking cyclobenzaprine. These tests are helpful when patients' medication lists are unknown and CA toxicity is suspected based on history, clinical presentation, and ECG findings. However, in patients known to take TCAs, the urine immunoassays are of limited use because the result does not correlate with serum CA levels.3

Imaging Studies

  • Chest radiography should be performed in cases of suspected aspiration or when respiratory symptoms are noted and may be used to rule out other causes of fever, tachycardia, and altered mental status.

Other Tests

Sinus tachycardia is the most common ECG finding in CA toxicity.

  • Measurement of limb-leads QRS duration can be used to assess the severity of CA exposure. A QRS interval greater than 100 milliseconds is the basis for treatment with bicarbonate (alkalinization).
  • Patients with a QRS interval less than 100 milliseconds are unlikely to develop seizures and arrhythmias. Patients with a QRS interval greater than 100 milliseconds have up to a 34% chance of developing seizures and up to a 14% chance of developing a life-threatening cardiac arrhythmia. With a QRS complex greater than 160 milliseconds, the chance of ventricular arrhythmias increases to 50%.
  • The amplitude of the R wave in lead aVR and the ratio of the R/S waves in aVR are greater in patients who developed seizures or dysrhythmias.
  • According to Liebelt et al, when the R wave in aVR equals 3 mm or more, the sensitivity and specificity for subsequent development of seizures or arrhythmias are 81% and 73%, respectively.4
  • ECG findings that can be observed in CA toxicity include sinus tachycardia; prolongation of the PR, QRS, and QTc intervals; nonspecific ST-segment and T-wave changes; AV block; right-axis deviation of the terminal 40-millisecond vector of the QRS complex in the frontal plane; and the Brugada pattern (downsloping ST-segment elevation in leads V1-V3 in association with right bundle branch block).5
  • A Brugada pattern was seen using ECG in 17% of patients with TCA toxicity in a retrospective study completed by Monteban-Kooistra et al.6 The ECG finding abnormalities resolved after administration of sodium bicarbonate.
  • A study of 98 consecutive cases of CA intoxication in France found that the mortality rate was 6.7% among patients with the Brugada electrocardiographic pattern and 2.4% among patients without it. However, the result is not statistically significant (p=0.39).7
  • Early recognition of conduction disturbances is important in suspected CA poisoning.

Procedures

  • GI decontamination may be helpful within the first several hours postingestion because CAs can slow gastric emptying through the anticholinergic activity.
    • Gastric lavage may be helpful in recovering and identifying the CA ingested. However, one study that compared the use of gastric lavage and activated charcoal versus charcoal alone showed no benefit in clinical outcome.8 Usually, lavage is recommended for patients who developed significant toxicity requiring endotracheal intubation and who presented after relatively recent ingestion (several hours).
    • Activated charcoal reduces the absorption of CAs. It may also be beneficial in cases of multisubstance ingestion. It should be administered only in patients who are able to protect the airway.
  • Endotracheal intubation is indicated if the patient cannot adequately maintain a safe airway.

More on Toxicity, Cyclic Antidepressants

Overview: Toxicity, Cyclic Antidepressants
Differential Diagnoses & Workup: Toxicity, Cyclic Antidepressants
Treatment & Medication: Toxicity, Cyclic Antidepressants
Follow-up: Toxicity, Cyclic Antidepressants
References
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References

  1. Heard K, Cain BS, Dart RC, Cairns CB. Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system. Acad Emerg Med. Dec 2001;8(12):1122-7. [Medline].

  2. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline]. [Full Text].

  3. Melanson SE, Lewandrowski EL, Griggs DA, Flood JG. Interpreting tricyclic antidepressant measurements in urine in an emergency department setting: comparison of two qualitative point-of-care urine tricyclic antidepressant drug immunoassays with quantitative serum chromatographic analysis. J Anal Toxicol. Jun 2007;31(5):270-5. [Medline].

  4. 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].

  5. Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24(3):205-14. [Medline].

  6. Monteban-Kooistra WE, van den Berg MP, Tulleken JE. Brugada electrocardiographic pattern elicited by cyclic antidepressants overdose. Intensive Care Med. Feb 2006;32(2):281-5. [Medline]. [Full Text].

  7. Goldgran-Toledano D, Sideris G, Kevorkian JP. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med. May 16 2002;346(20):1591-2. [Medline].

  8. Christophersen AB, Levin D, Hoegberg LC, Angelo HR, Kampmann JP. Activated charcoal alone or after gastric lavage: a simulated large paracetamol intoxication. Br J Clin Pharmacol. Mar 2002;53(3):312-7. [Medline].

  9. [Guideline] Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(3):203-33. [Medline]. [Full Text].

  10. McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med. Sep 1998;32(3 Pt 1):329-33. [Medline].

  11. Knudsen K, Abrahamsson J. Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline poisoning. Eur Heart J. May 1997;18(5):881-2. [Medline].

  12. Knudsen K, Abrahamsson J. Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat. Crit Care Med. Mar 1994;22(3):494-8. [Medline].

  13. O'Connor N, Greene S, Dargan P, Wyncoll D, Jones A. Prolonged clinical effects in modified-release amitriptyline poisoning. Clin Toxicol (Phila). 2006;44(1):77-80. [Medline].

  14. Rosenbaum TG, Kou M. Are one or two dangerous? Tricyclic antidepressant exposure in toddlers. J Emerg Med. Feb 2005;28(2):169-74. [Medline].

  15. 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].

  16. Frommer DA, Kulig KW, Marx JA, Rumack B. Tricyclic antidepressant overdose. A review. JAMA. Jan 23-30 1987;257(4):521-6. [Medline].

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

  18. Liebelt EL, Francis PD. Cyclic antidepressants. In: Goldfrank's Toxicologic Emergencies. 2002.

  19. 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].

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

  21. Roberge RJ, Krenzelok EP. Prolonged coma and loss of brainstem reflexes following amitriptyline overdose. Vet Hum Toxicol. Feb 2001;43(1):42-4. [Medline].

  22. Seger DL, Hantsch C, Zavoral T, Wrenn K. Variability of recommendations for serum alkalinization in tricyclic antidepressant overdose: a survey of U.S. Poison Center medical directors. J Toxicol Clin Toxicol. 2003;41(4):331-8. [Medline].

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Further Reading

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Keywords

tricyclic antidepressants, TCAs, CAs, cyclic antidepressant toxicity, cyclic antidepressant overdose, Brugada syndrome, cyclic antidepressants, cyclic antidepressant poisoning, tricyclic antidepressant poisoning, tricyclic antidepressant overdose, cyclic antidepressant overdose, TCA overdose, CA overdose, amitriptyline, doxepin, nortriptyline, TCA poisoning, CA poisoning

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Contributor Information and Disclosures

Author

Vivian Tsai, MD, MPH, Assistant Professor at Mount Sinai School of Medicine, Queens Hospital Center
Vivian Tsai, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate at Brooklyn
Mark A Silverberg, MD, FACEP, MMB is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Mark Biittner, MD, Consulting Staff, Department of Emergency Medicine, Sutter Roseville Medical Center
Mark Biittner, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Daniel M Joyce, MD, Consulting Staff, Department of Emergency Medicine, Saint Vincent's and Saint Mary's Medical
Daniel M Joyce, MD is a member of the following medical societies: American College of Emergency Physicians and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Miguel C Fernández, MD, FAAEM, FACEP, FACMT, FACCT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Miguel C Fernández, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & 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.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Department of Medicine, Clinical Pharmacology Division, Vanderbilt University; Managing Director, Tennessee Poison Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and 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.

 
 
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