Antidepressant Toxicity Workup

  • Author: Jeena Jacob, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Feb 8, 2010
 

Laboratory Studies

  • Quantitative screening or tricyclic serum concentrations are of minimal utility in the acute setting because serum levels do not correlate with acute toxicity secondary to pharmacologic properties such as large volume of distribution, pH-dependent protein binding, wide intrapatient variability of terminal elimination half-lives, and prolonged distribution phases. A toxicology screen may be helpful if concurrent ingestion is possible or if symptoms are not fully explained by tricyclic antidepressants (TCAs). An abbreviated screen for acetaminophen and aspirin coingestants usually is sufficient.
  • Electrolytes and glucose levels should be used to screen for anion gap acidosis that exists with other ingestions and to look for metabolic disturbances that can alter mental status, cause seizures, or change the ECG.
  • Serum pH
    • Blood gas analysis should be obtained to check pH with an attempt to maintain an alkaline environment (pH = 7.45-7.55).
    • Acidemia allows a greater degree of fast sodium channel binding by the TCA and produces a wider QRS on the ECG.
Next

Imaging Studies

  • Obtain a chest radiograph after intubation or if evidence of hypoxia, aspiration, or ARDS is present.
Previous
Next

Other Tests

An ECG has great utility in predicting the severity of toxicity.

  • ECG is the single most important test to determine diagnosis and prognosis.
  • Several studies have shown that a QRS duration greater than 100 milliseconds on an ECG is associated with an increased incidence of seizures, coma, need for intubation, hypotension, and dysrhythmias.
  • Prospective studies of patients with TCA overdose show that the sensitivity of an R-wave greater than 3 mm in aVR is similar to the sensitivity of a QRS=100 msec. Prospective data suggest that the typical period of QRS prolongation after severe tricyclic antidepressant ingestion is 12-18 hours but may be as long as 3 days.
  • Rightward deviation of QRS vector (a negative deflection in lead 1 and a positive final deflection in lead aVR) is associated with TCA toxicity.
  • Sinus tachycardia is a typical but nonspecific early sign of TCA toxicity.
  • Case reports have described ECGs in TCA toxicity mimicking acute myocardial infarction and the Brugada syndrome. One study found that 17% of patients that presented with TCA poisoning and ECG changes had Brugada pattern on ECG, which is a manifestation of intraventricular conduction disturbances.
  • Dysrhythmias are also nonspecific to TCA toxicity but important to respond to.
    • Ventricular tachycardia is the most common lethal dysrhythmia.
    • Torsade de pointes is uncommon in overdose but may occur in patients taking therapeutic doses.
  • Bradycardia and asystole are usually preterminal rhythms, although patients have been resuscitated from these with aggressive supportive care.
Previous
Next

Procedures

  • Endotracheal intubation
    • Aggressively manage airway for patients who present agitated or with a decreased level of consciousness. For these patients, endotracheal intubation may be required before gastric lavage or activated charcoal to prevent aspiration.
    • The patient should be hyperventilated after intubation. Check proper placement with a chest radiograph. The target PaCO2 is 30 mm Hg by ABG following intubation.
  • Gastric lavage
    • After the patient's airway, breathing, and circulation are secured, gastric lavage can be initiated in the symptomatic patient with an intentional overdose within 1.5-2 hours after ingestion.
    • If the patient exhibits declining mental status, the intubation should be performed first. Activated charcoal should be administered if the benefit of charcoal administration outweighs the risk of aspiration.
  • A central venous line may be helpful in administering medication and monitoring fluid status.
  • Hemodialysis
    • Hemodialysis and hemoperfusion are not effective and are not recommended for TCA poisoning.
    • The poor efficacy of hemodialysis probably is because only a small amount of free TCA is present in the serum. TCA is highly bound to serum proteins and tissues, with a large volume of distribution.
  • Only anecdotal evidence supports the efficacy of an intra-aortic balloon pump (IABP) for intractable hypotension.
Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Jeena Jacob, MD  PharmD, Medical Toxicology Fellow, Rocky Mountain Poison and Drug Center, Denver, CO

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

Disclosure: Nothing to disclose.

Coauthor(s)

Theodore I Benzer, MD, PhD  Assistant Professor in Medicine, Harvard Medical School; Director of Clinical Operations, 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 and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

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, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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.

Additional Contributors

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

References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila). Dec 2007;45(8):815-917. [Medline]. [Full Text].

  2. Busch SH, Frank RG, Leslie DL, Martin A, Rosenheck RA, Martin EG, et al. Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns?. Psychiatr Serv. Jan 2010;61(1):11-6. [Medline].

  3. Barry CL, Busch SH. News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics. Jan 2010;125(1):88-95. [Medline].

  4. Cassels C. FDA Suicide Warnings Change Antidepressant Prescribing Patterns, but Physicians Ignore Monitoring Recommendations. Medscape Today. Available at http://www.medscape.com/viewarticle/715952. Accessed February 8, 2010.

  5. Cassels C. FDA Suicide Warnings About Antidepressants Cut Rates of Depression Diagnosis and TreatmentExperts Call for FDA to Reconsider Black-Box Warning on Antidepressants. Medscape Today. Available at http://www.medscape.com/viewarticle/704235. Accessed February 8, 2010.

  6. 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].

  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. Barry JD, Durkovich DW, Williams SR. Vasopressin treatment for cyclic antidepressant overdose. J Emerg Med. Jul 2006;31(1):65-8. [Medline].

  9. Bebarta VS, Phillips S, Eberhardt A, et al. Incidence of Brugada electrocardiographic pattern and outcomes of these patients after intentional tricyclic antidepressant ingestion. Am J Cardiol. Aug 15 2007;100(4):656-60. [Medline].

  10. Fletcher SE, Case CL, Sallee FR, et al. Prospective study of the electrocardiographic effects of imipramine in children. J Pediatr. Apr 1993;122(4):652-4. [Medline].

  11. Graudins A, Dowsett RP, Liddle C. The toxicity of antidepressant poisoning: is it changing? A comparative study of cyclic and newer serotonin-specific antidepressants. Emerg Med (Fremantle). Dec 2002;14(4):440-6. [Medline].

  12. Høegholm A, Clementsen P. Hypertonic sodium chloride in severe antidepressant overdosage. J Toxicol Clin Toxicol. 1991;29(2):297-8. [Medline].

  13. 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].

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

  15. McCabe JL, Cobaugh DJ, Menegazzi JJ, et al. 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].

  16. McKenzie MS, McFarland BH. Trends in antidepressant overdoses. Pharmacoepidemiol Drug Saf. May 2007;16(5):513-23. [Medline].

  17. McKinney PE, Rasmussen R. Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution. Ann Emerg Med. Jul 2003;42(1):20-4. [Medline].

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

  19. Obrador D, Ballester M, Carrio I, et al. Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111In monoclonal antimyosin antibodies. Circulation. May 1994;89(5):2054-61. [Medline].

  20. Svens K, Ryrfeldt A. A study of mechanisms underlying amitriptyline-induced acute lung function impairment. Toxicol Appl Pharmacol. Dec 15 2001;177(3):179-87. [Medline].

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

  22. Tran TP, Panacek EA, Rhee KJ, et al. Response to dopamine vs norepinephrine in tricyclic antidepressant-induced hypotension. Acad Emerg Med. Sep 1997;4(9):864-8. [Medline].

  23. Woolf AD, Erdman AR, Nelson LS, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(3):203-33. [Medline].

  24. Zuidema X, Dünser MW, Wenzel V, et al. Terlipressin as an adjunct vasopressor in refractory hypotension after tricyclic antidepressant intoxication. Resuscitation. Feb 2007;72(2):319-23. [Medline].

 
Previous
Next
 
Toxicity, antidepressant. ECG shows the terminal R wave in aVR and the widened QRS complex associated with tricyclic antidepressant (TCA) toxicity.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
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.