Highlights & Basics
- Tricyclic antidepressant overdose should be suspected in patients with a history of depression, suicidality, and overdose presenting with a sudden deterioration in mental status and vital signs.
- At 1 to 2 hours after ingestion, there is a rapid decline in mental and cardiovascular status. Diagnosis is established on clinical grounds and classic ECG changes (sinus tachycardia progressing to wide complex tachycardia and ventricular arrhythmias with increasing severity of intoxication).
- Hypertonic sodium bicarbonate improves conduction abnormalities and hypotension.
- Management of arrhythmias involves correction of acidosis, hypoxia, and electrolyte imbalance. Antiarrhythmic drugs should generally be avoided.
- Hypotension usually responds to correction of hypoxia and administration of intravenous fluids and sodium bicarbonate. Treatment with vasopressors is controversial and should only be done in consultation with a medical toxicologist or intensive care specialist.
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Citations
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;45:203-233.[Abstract]
Body R, Bartram T, Azam F, et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J. 2011;28:347-368.[Abstract]
Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.[Abstract][Full Text]
American Heart Association. Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. 2020 [internet publication].[Full Text]
1. Henry JA, Alexander CA, Sener EK. Relative mortality from overdose of antidepressants. BMJ. 1995;310:221-224.[Abstract][Full Text]
2. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003;96:369-374.[Abstract][Full Text]
3. Buckley NA, Dawson AH, Whyte IM, et al. Greater toxicity in overdose of dothiepin than of other tricyclic antidepressants. Lancet. 1994;343:159-162.[Abstract]
4. Pacher P, Ungvari Z. Selective serotonin-reuptake inhibitor antidepressants increase the risk of falls and hip fractures in elderly people by inhibiting cardiovascular ion channels. Med Hypotheses. 2001;57:469-471.[Abstract]
5. Gummin DD, Mowry JB, Spyker DA, et al. 2022 Annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 40th annual report. Clin Toxicol (Phila). 2023 Oct;61(10):717-939.[Abstract][Full Text]
6. Tyrrell EG, Kendrick D, Sayal K, et al. Poisoning substances taken by young people: a population-based cohort study. Br J Gen Pract. 2018 Oct;68(675):e703-10.[Abstract][Full Text]
7. Morgan OW, Griffiths C, Majeed A. Association between mortality from suicide in England and antidepressant prescribing: an ecological study. BMC Public Health. 2004 Dec 21;4:63.[Abstract][Full Text]
8. Stafford RS, MacDonald EA, Finkelstein SN. National patterns of medication treatment for depression, 1987 to 2001. Prim Care Companion J Clin Psychiatry. 2001 Dec;3(6):232-5.[Abstract][Full Text]
9. Tamblyn R, Bates DW, Buckeridge DL, et al. Multinational comparison of new antidepressant use in older adults: a cohort study. BMJ Open. 2019 May 14;9(5):e027663.[Abstract][Full Text]
10. Bachmann CJ, Aagaard L, Burcu M, et al. Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012. Eur Neuropsychopharmacol. 2016 Mar;26(3):411-9.[Abstract]
11. Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. 2001;18:236-241.[Abstract][Full Text]
12. Barbey JT, Roose SP. SSRI safety in overdose. J Clin Psychiatry. 1998;59(suppl 15):42-48.[Abstract]
13. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-1120.[Abstract]
14. DeBattista C. Antidepressant drugs. In: Trevor AJ, Katzung B, Masters S, eds. Basic and clinical pharmacology. 11th ed. New York, NY: Lange, McGraw-Hill Medical Publishing Division; 2009.
15. Grunebaum MF, Ellis SP, Li S, et al. Antidepressants and suicide risk in the United States, 1985-1999. J Clin Psychiatry. 2004;65:1456-1462.[Abstract]
16. Beck AT, Kovacs M, Weissman A. Assessment of suicidal intention: the Scale for Suicide Ideation. J Consult Clin Psychol. 1979;47:343-352.[Abstract]
17. Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24:205-14.[Abstract]
18. Neimann JT, Bessen HA, Rothstein RJ, et al. Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. Am J Cardiol. 1986;57:1154-1159.[Abstract]
19. Boehnert M, 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. 1985;313:474-479.[Abstract]
20. Pentel P, Peterson CD. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980;9:588-590.[Abstract]
21. Bradberry SM, Thanacoody HK, Watt BE, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate. Toxicol Rev. 2005;24:195-204.[Abstract]
22. 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;45:203-233.[Abstract]
23. Foulke GE. Identifying toxicity risk early after antidepressant overdose. Am J Emerg Med. 1995;13:123-126.[Abstract]
24. Caravati EM, Bossart PJ. Demographic and electrocardiographic factors associated with severe tricyclic antidepressant toxicity. J Toxicol Clin Toxicol. 1991;29:31-43.[Abstract]
25. Body R, Bartram T, Azam F, et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J. 2011;28:347-368.[Abstract]
26. Emerman CL, Connors AF Jr, Burma GM. Level of consciousness as a predictor of complications following tricyclic overdose. Ann Emerg Med. 1987;16:326-330.[Abstract]
27. Callaham M, Kassel D. Epidemiology of fatal tricyclic antidepressant ingestion: implications for management. Ann Emerg Med. 1985;14:1-9.[Abstract]
28. Dargan PI, Colbridge MG, Jones AL. The management of tricyclic antidepressant poisoning: the role of gut decontamination, extracorporeal procedures and fab antibody fragments. Toxicol Rev. 2005;24:187-194.[Abstract]
29. Williams JM, Hollingshed MJ, Vasilakis A, et al. Extracorporeal circulation in the management of severe tricyclic antidepressant overdose. Am J Emerg Med. 1994;12:456-458.[Abstract]
30. Goodwin DA, Lally KP, Null DM Jr. Extracorporeal membrane oxygenation support for cardiac dysfunction from tricyclic antidepressant overdose. Crit Care Med. 1993;21:625-627.[Abstract]
31. Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.[Abstract][Full Text]
32. Sasyniuk BI, Jhamandas V. Mechanism of reversal of toxic effects of amitriptyline on cardiac Purkinje fibers by sodium bicarbonate. J Pharmacol Exp Ther. 1984;231:387-394.[Abstract]
33. Sensky PR, Olczak SA. High-dose intravenous glucagon in severe tricyclic poisoning. Postgrad Med J. 1999;75:611-612.[Abstract][Full Text]
34. Sener EK, Gabe S, Henry JA. Response to glucagon in imipramine overdose. J Toxicol Clin Toxicol. 1995;33:51-53.[Abstract]
35. Zuidema X, Dünser MW, Wenzel V, et al. Terlipressin as an adjunct vasopressor in refractory hypotension after tricyclic antidepressant intoxication. Resuscitation. 2007;72:319-323.[Abstract]
36. Barry JD, Durkovich DW, Williams SR. Vasopressin treatment for cyclic antidepressant overdose. J Emerg Med. 2006;31:65-68.[Abstract]
37. Knudsen K, Abrahamsson J. Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline poisoning. Eur Heart J. 1997;18:881-882.[Abstract][Full Text]
38. Citak A, Soysal DD, Uçsel R, et al. Efficacy of long duration resuscitation and magnesium sulphate treatment in amitriptyline poisoning. Eur J Emerg Med. 2002;9:63-66.[Abstract]
39. Foianini A, Wiegand TJ, Benowitz N. What is the role of lidocaine or phenytoin in tricyclic antidepressant-induced cardiotoxicity? Clin Toxicol (Phila). 2010;48:325-330.[Abstract]
40. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review. Acad Emerg Med. 2009;16:815-824.[Abstract]
41. Cave G, Harvey M, Graudins A. Review article: intravenous lipid emulsion as antidote: a summary of published human experience. Emerg Med Australas. 2011;23:123-141.[Abstract][Full Text]
42. Jamaty C, Bailey B, Larocque A, et al. Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies. Clin Toxicol (Phila). 2010;48:1-27.[Abstract]
43. Callaham M, Schumaker H, Pentel P. Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning. J Pharmacol Exp Ther. 1988;245:216-220.[Abstract]
44. American Heart Association. Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. 2020 [internet publication].[Full Text]
45. European Resuscitation Council. European Resuscitation Council guidelines for resuscitation, 2021. 2021 [internet publication].[Full Text]
46. Resuscitation Council (UK). Paediatric advanced life support. May 2021 [internet publication].[Full Text]
47. Resuscitation Council (UK). Adult advanced life support. May 2021 [internet publication]. [Full Text]
