Skip to main content
SpringerLink
Log in

Tricyclic Antidepressant Poisoning

Cardiovascular Toxicity

  • Review Article
  • Published:
Toxicological Reviews

Abstract

Tricyclic antidepressants remain a common cause of fatal drug poisoning as a result of their cardiovascular toxicity manifested by ECG abnormalities, arrhythmias and hypotension. Dosulepin and amitriptyline appear to be particularly toxic in overdose. The principal mechanism of toxicity is cardiac sodium channel blockade, which increases the duration of the cardiac action potential and refractory period and delays atrioventricular conduction. Electrocardiographic changes include prolongation of the PR, QRS and QT intervals, nonspecific ST segment and T wave changes, atrioventricular block, right axis deviation of the terminal 40ms vector of the QRS complex in the frontal plane (T 40ms axis) and the Brugada pattern (downsloping ST segment elevation in leads V1–V3 in association with right bundle branch block). Maximal changes in the QRS duration and the T 40ms axis are usually present within 12 hours of ingestion but may take up to a week to resolve. Sinus tachycardia is the most common arrhythmia due to anticholinergic activity and inhibition of norepinephrine uptake by tricyclic antidepressants but bradyarrhythmias (due to atrioventricular block) and tachyarrhythmias (supraventricular and ventricular) may occur. Torsade de pointes occurs uncommonly. Hypotension results from a combination of reduced myocardial contractility and reduced systemic vascular resistance due to α-adrenergic blockade. Life-threatening arrhythmias and death due to tricyclic antidepressant poisoning usually occurs within 24 hours of ingestion. Rapid deterioration is common. Level of consciousness at presentation is the most sensitive clinical predictor of serious complications. Although a QRS duration >100ms and a rightward T 40ms axis appear to be better predictors of cardiovascular toxicity than the plasma tricyclic drug concentration, they have at best moderate sensitivity and specificity for predicting complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Bradberry SM, Thanacoody HKR, Watt BE, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate. Toxicol Rev 2005; 24(3): 195–204

    Article  PubMed  CAS  Google Scholar 

  2. Thomas SHL, Bevan L, Bhattacharyya S, et al. Presentation of poisoned patients to accident and emergency departments in the North of England. Hum Exp Toxicol 1996; 15: 466–70

    Article  PubMed  CAS  Google Scholar 

  3. Buckley NA, Whyte IM, Dawson AH, et al. Self-poisoning in Newcastle, 1987–1992. Med J Aust 1995; 162: 190–3

    PubMed  CAS  Google Scholar 

  4. Obafunwa JO, Busuttil A. Deaths from substance overdose in the Lothian and Borders region of Scotland (1983–1991). Hum Exp Toxicol 1994; 13: 401–6

    Article  PubMed  CAS  Google Scholar 

  5. Henry JA, Alexander CA, Sener EK. Relative mortality from overdose of antidepressants. BMJ 1995; 310: 221–4

    Article  PubMed  CAS  Google Scholar 

  6. Shah R, Uren Z, Baker A, et al. Deaths from antidepressants in England and Wales 1993–1997: analysis of a new national database. Psychol Med 2001; 31: 1203–10

    Article  PubMed  CAS  Google Scholar 

  7. Glauser J. Tricyclic antidepressant poisoning. Cleve Clin J Med 2000; 67: 704–19

    PubMed  CAS  Google Scholar 

  8. Buckley NA, Dawson AH, Whyte IM, et al. Greater toxicity in overdose of dothiepin than of other tricyclic antidepressants. Lancet 1994; 343: 159–62

    Article  PubMed  CAS  Google Scholar 

  9. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Q J Med 2003; 96: 369–74

    Article  CAS  Google Scholar 

  10. Buckley NA, McManus PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002; 325: 1332–3

    Article  PubMed  Google Scholar 

  11. Dziukas LJ, Vohra J. Tricyclic antidepressant poisoning. Med J Aust 1991; 154: 344–50

    PubMed  CAS  Google Scholar 

  12. Hurst HE, Jarboe CH. Clinical findings, elimination pharmacokinetics, and tissue drug concentrations following a fatal amitriptyline intoxication. J Toxicol Clin Toxicol 1981; 18: 119–25

    Article  CAS  Google Scholar 

  13. Spiker DG, Biggs JT. Tricyclic antidepressants: prolonged plasma levels after overdose. JAMA 1976; 236: 1711–2

    Article  PubMed  CAS  Google Scholar 

  14. Vohra J, Burrows G, Hunt D, et al. The effect of toxic and therapeutic doses of tricyclic antidepressant drugs on intracardiac conduction. Eur J Cardiol 1975; 3: 219–27

    PubMed  CAS  Google Scholar 

  15. Teschemacher AG, Seward EP, Hancox JC, et al. Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. Br J Pharmacol 1999; 128: 479–85

    Article  PubMed  CAS  Google Scholar 

  16. Brennan FJ. Electrophysiologic effects of imipramine and doxepin on normal and depressed cardiac Purkinje fibers. Am J Cardiol 1980; 46: 599–606

    Article  PubMed  CAS  Google Scholar 

  17. Steeds RP, Muthusamy R. Abnormal ventricular conduction following dothiepin overdose simulating acute myocardial infarction. Heart 2000; 83: 289

    Article  PubMed  CAS  Google Scholar 

  18. Zakynthinos E, Vassilakopoulos T, Roussos C, et al. Abnormal atrial and ventricular repolarisation resembling myocardial injury after tricyclic antidepressant drug intoxication. Heart 2000; 83: 353–4

    Article  PubMed  CAS  Google Scholar 

  19. Krayenbuehl P-A, Christen S. Tricyclic antidepressant overdose mimicking myocardial infarction. J Clin Basic Cardiol 2002; 5: 197

    Google Scholar 

  20. Chamsi-Pasha H, Barnes PC. Myocardial infarction: a complication of amitriptyline overdose. Postgrad Med J 1988; 64: 968–70

    Article  PubMed  CAS  Google Scholar 

  21. Arya B, Hirudayaraj P, Willmer K. Myocardial infarction: a rare complication of dothiepin overdose. Int J Cardiol 2004; 96: 493–4

    Article  PubMed  Google Scholar 

  22. Frommer DA, Kulig KW, Marx JA, et al. Tricyclic antidepressant overdose: a review. JAMA 1987; 257: 521–6

    Article  PubMed  CAS  Google Scholar 

  23. Langou RA, Van Dyke C, Tahan SR, et al. Cardiovascular manifestations of tricyclic antidepressant overdose. Am Heart J 1980; 100: 458–64

    Article  PubMed  CAS  Google Scholar 

  24. Pellinen TJ, Farkkila M, Heikkila J, et al. Electrocardiographic and clinical features of tricyclic antidepressant intoxication. Ann Clin Res 1987; 19: 12–7

    PubMed  CAS  Google Scholar 

  25. Goldberg RJ, Capone RJ, Hunt JD. Cardiac complications following tricyclic antidepressant overdose: issues for monitoring policy. JAMA 1985; 254: 1772–5

    Article  PubMed  CAS  Google Scholar 

  26. Niemann JT, Bessen HA, Rothstein RJ, et al. Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. Am J Cardiol 1986; 57: 1154–9

    Article  PubMed  CAS  Google Scholar 

  27. Wolfe TR, Caravati EM, Rollins DE. Terminal 40-ms frontal plane QRS axis as a marker for tricyclic antidepressant overdose. Ann Emerg Med 1989; 18: 348–51

    Article  PubMed  CAS  Google Scholar 

  28. Lavoie FW, Gansert GG, Weiss RE. Value of initial ECG findings and plasma drug levels in cyclic antidepressant overdose. Ann Emerg Med 1990; 19: 696–700

    Article  PubMed  CAS  Google Scholar 

  29. Chow BJ, Gollob M, Birnie D. Brugada syndrome precipitated by a tricyclic antidepressant. Heart 2005; 91: 651

    Article  PubMed  CAS  Google Scholar 

  30. Babaliaros VC, Hurst JW. Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine. Clin Cardiol 2002; 25: 395–8

    Article  PubMed  Google Scholar 

  31. Bolognesi R, Tsialtas D, Vasini P, et al. Abnormal ventricular repolarization mimicking myocardial infarction after heterocyclic antidepressant overdose. Am J Cardiol 1997; 79: 242–5

    Article  PubMed  CAS  Google Scholar 

  32. Tada H, Sticherling C, Oral H, et al. Brugada syndrome mimicked by tricyclic antidepressant overdose. J Cardiovasc Electrophysiol 2001; 12: 275

    Article  PubMed  CAS  Google Scholar 

  33. Bigwood B, Galler D, Amir N, et al. Brugada syndrome following tricyclic antidepressant overdose. Anaesth Intensive Care 2005; 33: 266–70

    PubMed  CAS  Google Scholar 

  34. Goldgran-Toledano D, Sideris G, Kevorkian J-P. Overdose of cyclic antidepressants and the Brugada syndrome. N Engl J Med 2002; 346: 1591–2

    Article  PubMed  Google Scholar 

  35. Liebelt EL, Ulrich A, Francis PD, et al. Serial electrocardiogram changes in acute tricyclic antidepressant overdoses. Crit Care Med 1997; 25: 1721–6

    Article  PubMed  CAS  Google Scholar 

  36. Shannon MW. Duration of QRS disturbances after severe tricyclic antidepressant intoxication. J Toxicol Clin Toxicol 1992; 30: 377–86

    Article  PubMed  CAS  Google Scholar 

  37. Noble J, Matthew H. Acute poisoning by tricyclic antidepressants: clinical features and management of 100 patients. J Toxicol Clin Toxicol 1969; 2: 403–21

    Article  Google Scholar 

  38. Bramble MG, Lishman AH, Purdon J, et al. An analysis of plasma levels and 24-hour ECG recordings in tricyclic antidepressant poisoning: implications for management. Q J Med 1985; 56: 357–66

    PubMed  CAS  Google Scholar 

  39. Fasoli RA, Glauser FL. Cardiac arrhythmias and ECG abnormalities in tricyclic antidepressant overdose. J Toxicol Clin Toxicol 1981; 18: 155–63

    Article  CAS  Google Scholar 

  40. Thorstrand C. Clinical features in poisonings by tricyclic antidepressants with special reference to the ECG. Acta Med Scand 1976; 199: 337–44

    Article  PubMed  CAS  Google Scholar 

  41. Callaham M, Kassel D. Epidemiology of fatal tricyclic antidepressant ingestion: implications for management. Ann Emerg Med 1985; 14: 1–9

    Article  PubMed  CAS  Google Scholar 

  42. Alter P, Tontsch D, Grimm W. Doxepin-induced torsade de pointes tachycardia. Ann Intern Med 2001; 135: 384–5

    PubMed  CAS  Google Scholar 

  43. Davison ET. Amitriptyline-induced torsade de pointes: successful therapy with atrial pacing. J Electrocardiol 1985; 18: 299–301

    Article  PubMed  CAS  Google Scholar 

  44. Crome P, Newman B. Fatal tricyclic antidepressant poisoning. J R Soc Med 1979; 72: 649–53

    PubMed  CAS  Google Scholar 

  45. Hulten BA, Heath A. Clinical aspects of tricyclic antidepressant poisoning. Acta Med Scand 1983; 213: 275–8

    Article  PubMed  CAS  Google Scholar 

  46. Pentel P, Sioris L. Incidence of late arrhythmias following tricyclic antidepressant overdose. J Toxicol Clin Toxicol 1981; 18: 543–8

    Article  CAS  Google Scholar 

  47. Desager JP, Leonard JP, Vanderbist M, et al. Reduced cardiac output and renal blood flow during amitriptyline intoxication in conscious rabbits. Toxicol Appl Pharmacol 1979; 47: 445–9

    Article  PubMed  CAS  Google Scholar 

  48. Heard K, Cain BS, Dart RC, et al. Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system. Acad Emerg Med 2001; 8: 1122–7

    Article  PubMed  CAS  Google Scholar 

  49. Shannon M, Merola J, Lovejoy Jr FH. Hypotension in severe tricyclic antidepressant overdose. Am J Emerg Med 1988; 6: 439–42

    Article  PubMed  CAS  Google Scholar 

  50. Foulke GE, Albertson TE, Walby WF. Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course. Am J Emerg Med 1986; 4: 496–500

    Article  PubMed  CAS  Google Scholar 

  51. Emerman CL, Connors Jr AF, Burma GM. Level of consciousness as a predictor of complications following tricyclic overdose. Ann Emerg Med 1987; 16: 326–30

    Article  PubMed  CAS  Google Scholar 

  52. Matthew H, Lawson AAH. Acute barbiturate poisoning: a review of two years experience. Q J Med 1966; 35: 539–52

    Google Scholar 

  53. Hultén B-Å, Adams R, Askenasi R, et al. Predicting severity of tricyclic antidepressant overdose. J Toxicol Clin Toxicol 1992; 30: 161–70

    Article  PubMed  Google Scholar 

  54. Foulke GE. Identifying toxicity risk early after antidepressant overdose. Am J Emerg Med 1995; 13: 123–6

    Article  PubMed  CAS  Google Scholar 

  55. Caravati EM, Bossart PJ. Demographic and electrocardiographic factors associated with severe tricyclic antidepressant toxicity. J Toxicol Clin Toxicol 1991; 29: 31–43

    Article  PubMed  CAS  Google Scholar 

  56. Ellison DW, Pentel PR. Clinical features and consequences of seizures due to cyclic antidepressant overdose. Am J Emerg Med 1989; 7: 5–10

    Article  PubMed  CAS  Google Scholar 

  57. Lipper B, Bell A, Gaynor B. Recurrent hypotension immediately after seizures in nortriptyline overdose. Am J Emerg Med 1994; 12: 452–3

    Article  PubMed  CAS  Google Scholar 

  58. Taboulet P, Michard F, Muszynski J, et al. Cardiovascular repercussions of seizures during cyclic antidepressant poisoning. J Toxicol Clin Toxicol 1995; 33: 205–11

    Article  PubMed  CAS  Google Scholar 

  59. Boehnert MT, Lovejoy Jr FH. 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: 474–9

    Article  PubMed  CAS  Google Scholar 

  60. Foulke GE, Albertson TE. QRS interval in tricyclic antidepressant overdosage inaccuracy as a toxicity indicator in emergency settings. Ann Emerg Med 1987; 16: 160–3

    Article  PubMed  CAS  Google Scholar 

  61. Buckley NA, O’Connell DL, Whyte IM, et al. Interrater agreement in the measurement of QRS interval in tricyclic antidepressant overdose: implications for monitoring and research. Ann Emerg Med 1996; 28: 515–9

    Article  PubMed  CAS  Google Scholar 

  62. 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 1995; 26: 195–201

    Article  PubMed  CAS  Google Scholar 

  63. Buckley NA, Chevalier S, Leditschke IA, et al. The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose. Crit Care 2003; 7: R101–7

    Article  PubMed  Google Scholar 

  64. Petit JM, Spiker DG, Ruwitch JF, et al. Tricyclic antidepressant plasma levels and adverse effects after overdose. Clin Pharmacol Ther 1977; 21: 47–51

    PubMed  CAS  Google Scholar 

  65. Spiker DG, Weiss AN, Chang SS, et al. Tricyclic antidepressant overdose: clinical presentation and plasma levels. Clin Pharmacol Ther 1975; 18: 539–46

    PubMed  CAS  Google Scholar 

  66. Hanzlick RL. Postmortem blood concentrations of parent tricyclic antidepressant (TCA) drugs in 11 cases of suicide. Am J Forensic Med Pathol 1984; 5: 11–3

    Article  PubMed  CAS  Google Scholar 

  67. Rudorfer MV. Cardiovascular changes and plasma drug levels after amitriptyline overdose. J Toxicol Clin Toxicol 1982; 19: 67–78

    Article  PubMed  CAS  Google Scholar 

  68. Marshall JB. Tricyclic overdose. JAMA 1980; 244: 1900

    Article  PubMed  CAS  Google Scholar 

  69. Amitai Y, Erickson T, Kennedy EJ, et al. Tricyclic antidepressants in red cells and plasma: correlation with impaired intraventricular conduction in acute overdose. Clin Pharmacol Ther 1993; 54: 219–27

    Article  PubMed  CAS  Google Scholar 

  70. 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: 877–88

    Article  PubMed  CAS  Google Scholar 

  71. Callaham M. Admission criteria for tricyclic antidepressant ingestion. West J Med 1982; 137: 425–9

    PubMed  CAS  Google Scholar 

  72. Sedal L, Korman MG, Williams PO, et al. Overdosage of tricyclic antidepressants: a report of two deaths and a prospective study of 24 patients. Med J Aust 1972; 2: 74–9

    PubMed  CAS  Google Scholar 

  73. Masters AB. Delayed death in imipramine poisoning. BMJ 1967; 3: 866–7

    Article  PubMed  CAS  Google Scholar 

  74. McAlpine SB, Calabro JJ, Robinson MD, et al. Late death in tricyclic antidepressant overdose revisited. Ann Emerg Med 1986; 15: 1349–52

    Article  PubMed  CAS  Google Scholar 

  75. Bloodworth L, Wilson A, Collins P, et al. Severe dothiepin intoxication: a report of two cases. Postgrad Med J 1984; 60: 442–4

    Article  PubMed  CAS  Google Scholar 

  76. Babb SV, Dunlop SR. Case report of sudden and unexpected death after tricyclic overdose. Am J Psychiatry 1985; 142: 275–6

    PubMed  CAS  Google Scholar 

  77. Chiu TF, Yang CC, Ger J, et al. Adult respiratory distress syndrome and late death following imipramine overdose: a case report. Chin Med J 1994; 54: 436–41

    CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Wolfson Unit of Clinical Pharmacology, School of Clinical and Laboratory Sciences, University of Newcastle, UK

    H. K. Ruben Thanacoody & Simon H. L. Thomas

  2. National Poisons Information Service (Newcastle Centre), Newcastle upon Tyne, NE2 4HH, UK

    H. K. Ruben Thanacoody & Simon H. L. Thomas

Authors
  1. H. K. Ruben Thanacoody
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon H. L. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thanacoody, H.K.R., Thomas, S.H.L. Tricyclic Antidepressant Poisoning. Toxicol Rev 24, 205–214 (2005). https://doi.org/10.2165/00139709-200524030-00013

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00139709-200524030-00013

Keywords

Search

Navigation