Toxicological Reviews

, Volume 24, Issue 3, pp 187–194 | Cite as

The Management of Tricyclic Antidepressant Poisoning

The Role of Gut Decontamination, Extracorporeal Procedures and Fab Antibody Fragments
  • Paul I. Dargan
  • Mark G. Colbridge
  • Alison L. Jones
Review Article


Although there have been descriptive, uncontrolled clinical reports of removal of tablet debris by gastric lavage, there have been no clinical studies that have demonstrated that this has any impact on outcome in patients with tricyclic antidepressant (TCA) poisoning. There is also the possibility that lavage may increase drug absorption by pushing tablets into the small intestine. Furthermore, gastric lavage in patients with TCA poisoning may induce hypoxia and a tachycardia potentially increasing the risk of severe complications such as arrhythmias and convulsions. In view of the paucity of evidence that gastric lavage removes a significant amount of drug and the risk of complications associated with the procedure, the routine use of gastric lavage in the management of patients with TCA poisoning is not appropriate.

Volunteer studies have shown generally that activated charcoal is more likely to reduce drug absorption if it is administered within 1 hour of drug ingestion. In the one volunteer study that looked at later administration of activated charcoal, there was a 37% decrease in plasma concentration associated with administration of activated charcoal at 2 hours post-ingestion. There have been no clinical studies that enable an estimate of the effect of activated charcoal administration on outcome in the management of patients with TCA poisoning.

Volunteer studies have shown that multiple-dose activated charcoal increases the elimination of therapeutic doses of amitriptyline and nortriptyline, but not of doxepin or imipramine; however, these studies cannot be directly extrapolated to the management of patients with TCA poisoning. There have been no well designed controlled studies that have assessed the impact of multiple-dose activated charcoal in the management of patients with TCA poisoning. Because of the large volume of distribution of TCAs, it would not be expected that their elimination would be significantly increased by multiple-dose activated charcoal.

Haemoperfusion, haemodialysis and the combination of these procedures do not result in significant removal of TCAs and are not recommended in the management of patients with TCA poisoning.


  1. 1.
    Krenzelok EP, McGuigan M, Lheureux P. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement: ipecac syrup. J Toxicol Clin Toxicol 1997; 35: 699–709PubMedCrossRefGoogle Scholar
  2. 2.
    Callaham M, Kassel D. Epidemiology of fatal tricyclic antidepressant ingestion: implications for management. Ann Emerg Med 1985; 14: 1–9PubMedCrossRefGoogle Scholar
  3. 3.
    Albertson TE, Derlet RW, Foulke GE, et al. Superiority of activated charcoal alone compared with ipecac and activated charcoal in the treatment of toxic ingestions. Ann Emerg Med 1989; 18: 56–9PubMedCrossRefGoogle Scholar
  4. 4.
    Auerbach PS, Osterloh J, Braun O, et al. Efficacy of gastric emptying gastric lavage versus emesis induced with ipecac. Ann Emerg Med 1986; 15: 692–8PubMedCrossRefGoogle Scholar
  5. 5.
    Young WF, Bivins HG. Evaluation of gastric emptying using radionuclides: gastric lavage versus ipecac-induced emesis. Ann Emerg Med 1993; 22: 1423–7PubMedCrossRefGoogle Scholar
  6. 6.
    Saetta JP, Quinton DN. Residual gastric content after gastric lavage and ipecacuanha-induced emesis in self-poisoned patients: an endoscopic study. J R Soc Med 1991; 84: 35–8PubMedGoogle Scholar
  7. 7.
    Vale JA. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement: gastric lavage. J Toxicol Clin Toxicol 1997; 35: 711–9PubMedCrossRefGoogle Scholar
  8. 8.
    Comstock EG, Faulkner TP, Boisaubin EV, et al. Studies on the efficacy of gastric lavage as practiced in a large metropolitan hospital. J Toxicol Clin Toxicol 1981; 18: 581–97CrossRefGoogle Scholar
  9. 9.
    Watson WA, Leighton J, Guy J, et al. Recovery of cyclic antidepressants with gastric lavage. J Emerg Med 1989; 7: 373–7PubMedCrossRefGoogle Scholar
  10. 10.
    Bosse GM, Barefoot JA, Pfeifer MP, et al. Comparison of three methods of gut decontamination in tricyclic antidepressant overdose. J Emerg Med 1995; 13: 203–9PubMedCrossRefGoogle Scholar
  11. 11.
    Gard H, Knapp D, Walle T, et al. Qualitative and quantitative studies on the disposition of amitriptyline and other tricyclic antidepressant drugs in man as it relates to the management of the overdosed patient. J Toxicol Clin Toxicol 1973; 6: 571–84CrossRefGoogle Scholar
  12. 12.
    Jorens PG, Joosens EJ, Nagler JM. Changes in arterial oxygen tension after gastric lavage for drug overdose. Hum Exp Toxicol 1991; 10: 221–4PubMedCrossRefGoogle Scholar
  13. 13.
    Thompson AM, Robins JB, Prescott LF. Changes in cardiorespiratory function during gastric lavage for drug overdose. Hum Toxicol 1987; 6: 215–8PubMedCrossRefGoogle Scholar
  14. 14.
    Mariani PJ, Pook N. Gastrointestinal tract perforation with charcoal peritoneum complicating orogastric intubation and lavage. Ann Emerg Med 1993; 22: 606–9PubMedCrossRefGoogle Scholar
  15. 15.
    Askenasi R, Abramowicz M, Jeanmart J, et al. Esophageal perforation: an unusual complication of gastric lavage. Ann Emerg Med 1984; 13: 146PubMedCrossRefGoogle Scholar
  16. 16.
    Allan BC. The role of gastric lavage in the treatment of patients suffering from barbiturate overdose. Med J Aust 1961; 2: 513–4Google Scholar
  17. 17.
    Saetta JP, March S, Gaunt ME, et al. Gastric emptying procedures in the self-poisoned patient: are we forcing gastric content beyond the pylorus? J R Soc Med 1991; 84: 274–6PubMedGoogle Scholar
  18. 18.
    Chyka PA, Seger D. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement: single-dose activated charcoal. J Toxicol Clin Toxicol 1997; 35: 721–41PubMedCrossRefGoogle Scholar
  19. 19.
    Dawling S, Crome P, Braithwaite R. Effect of delayed administration of activated charcoal on nortriptyline absorption. Eur J Clin Pharmacol 1978; 14: 445–7PubMedCrossRefGoogle Scholar
  20. 20.
    Crome P, Dawling S, Braithwaite RA, et al. Effect of activated charcoal on absorption of nortriptyline. Lancet 1977; II: 1203–5CrossRefGoogle Scholar
  21. 21.
    Alván G. Effect of activated charcoal on plasma levels of nortriptyline after single doses in man. Eur J Clin Pharmacol 1973; 5: 236–8CrossRefGoogle Scholar
  22. 22.
    Kärkkäinen S, Neuvonen PJ. Pharmacokinetics of amitriptyline influenced by oral charcoal and urine pH. Int J Clin Pharmacol Ther Toxicol 1986; 24: 326–32PubMedGoogle Scholar
  23. 23.
    Scheinin M, Virtanen R, Iisalo E. Effect of single and repeated doses of activated charcoal on the pharmacokinetics of doxepin. Int J Clin Pharmacol Ther Toxicol 1985; 23: 38–42PubMedGoogle Scholar
  24. 24.
    Rosenberg J, Benowitz NL, Pond S. Pharmacokinetics of drug overdose. Clin Pharmacokinet 1981; 6: 161–92PubMedCrossRefGoogle Scholar
  25. 25.
    Hedges JR, Otten EJ, Schroeder TJ, et al. Correlation of initial amitriptyline concentration reduction with activated charcoal therapy in overdose patients. Am J Emerg Med 1987; 5: 48–51PubMedCrossRefGoogle Scholar
  26. 26.
    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: 474–9PubMedCrossRefGoogle Scholar
  27. 27.
    Hultén B-Å, Adams R, Askenasi R, et al. Predicting severity of tricyclic antidepressant overdose. J Toxicol Clin Toxicol 1992; 30: 161–70PubMedCrossRefGoogle Scholar
  28. 28.
    Hultén B-Å, Heath A, Knudsen K, et al. Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics. J Toxicol Clin Toxicol 1992; 30: 171–9PubMedCrossRefGoogle Scholar
  29. 29.
    Hultén B-A, Adams R, Askenasi R, et al. Activated charcoal in tricyclic antidepressant poisoning. Hum Toxicol 1988; 7: 307–10PubMedCrossRefGoogle Scholar
  30. 30.
    Crome P, Adams R, Ali C, et al. Activated charcoal in tricyclic antidepressant poisoning: pilot controlled clinical trial. Hum Toxicol 1983; 2: 205–9PubMedCrossRefGoogle Scholar
  31. 31.
    Underhill TJ, Greene MK, Dove AF. A comparison of the efficacy of gastric lavage, ipecacuanha and activated charcoal in the emergency management of paracetamol overdose. Arch Emerg Med 1990; 7: 148–54PubMedGoogle Scholar
  32. 32.
    Crockett R, Krishel SJ, Manoguerra A, et al. Prehospital use of activated charcoal: a pilot study. J Emerg Med 1996; 14: 335–8PubMedCrossRefGoogle Scholar
  33. 33.
    Pollack MM, Dunbar BS, Holbrook PR, et al. Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10: 528–9PubMedCrossRefGoogle Scholar
  34. 34.
    Justiniani FR, Hippalgaonkar R, Martinez LO. Charcoal-containing empyema complicating treatment for overdose. Chest 1985; 87: 404–5PubMedCrossRefGoogle Scholar
  35. 35.
    Elliott CG, Colby TV, Kelly TM, et al. Charcoal lung: bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96: 672–4PubMedCrossRefGoogle Scholar
  36. 36.
    Silberman H, Davis SM, Lee A. Activated charcoal aspiration. N C Med J 1990; 51: 79–80PubMedGoogle Scholar
  37. 37.
    Pond SM, Lewis-Driver DJ, Williams GM, et al. Gastric emptying in acute overdose: a prospective randomised controlled trial. Med J Aust 1995; 163: 345–9PubMedGoogle Scholar
  38. 38.
    Menzies DG, Busuttil A, Prescott LF. Fatal pulmonary aspiration of oral activated charcoal. BMJ 1988; 297: 459–60PubMedCrossRefGoogle Scholar
  39. 39.
    Harris CR, Filandrinos D. Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22: 1470–3PubMedCrossRefGoogle Scholar
  40. 40.
    Sabga E, Dick A, Lertzman M, et al. Direct administration of charcoal into the lung and pleural cavity. Ann Emerg Med 1997; 30: 695–7PubMedCrossRefGoogle Scholar
  41. 41.
    Merigian KS, Woodard M, Hedges JR, et al. Prospective evaluation of gastric emptying in the self-poisoned patient. Am J Emerg Med 1990; 8: 479–83PubMedCrossRefGoogle Scholar
  42. 42.
    Kornberg AE, Dolgin J. Pediatric ingestions: charcoal alone versus ipecac and charcoal. Ann Emerg Med 1991; 20: 648–51PubMedCrossRefGoogle Scholar
  43. 43.
    Tenebein M. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement: whole bowel irrigation. J Toxicol Clin Toxicol 1997; 35: 753–62CrossRefGoogle Scholar
  44. 44.
    Vale JA, Krenzelok EP, Barceloux DG. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999; 37: 731–51CrossRefGoogle Scholar
  45. 45.
    Gram LF. Plasma level monitoring of tricyclic antidepressant therapy. Clin Pharmacokinet 1977; 2: 237–51PubMedCrossRefGoogle Scholar
  46. 46.
    Goldberg MJ, Park GD, Spector R, et al. Lack of effect of oral activated charcoal on imipramine clearance. Clin Pharmacol Ther 1985; 38: 350–3PubMedCrossRefGoogle Scholar
  47. 47.
    Swartz CM, Sherman A. The treatment of tricyclic antidepressant overdose with repeated charcoal. J Clin Psychopharmacol 1984; 4: 336–40PubMedCrossRefGoogle Scholar
  48. 48.
    Spiker DG, Biggs JT. Tricyclic antidepressants: prolonged plasma levels after overdose. JAMA 1976; 236: 1711–2PubMedCrossRefGoogle Scholar
  49. 49.
    Hulten B-A, Heath A, Knudsen K, et al. Amitriptyline and amitriptyline metabolites in blood and cerebrospinal fluid following human overdose. J Toxicol Clin Toxicol 1992; 30: 181–201PubMedCrossRefGoogle Scholar
  50. 50.
    Ilett KF, Hackett LP, Dusci LJ, et al. Disposition of dothiepin after overdose: effects of repeated-dose activated charcoal. Ther Drug Monit 1991; 13: 485–9PubMedCrossRefGoogle Scholar
  51. 51.
    Gomez HF, Brent JA, Munoz DC, et al. Charcoal stercolith with intestinal perforation in a patient treated for amitriptyline ingestion. J Emerg Med 1994; 12: 57–60PubMedCrossRefGoogle Scholar
  52. 52.
    Ray MJ, Padin DR, Condie JD, et al. Charcoal bezoar: small-bowel obstruction secondary to amitriptyline overdose therapy. Dig Dis Sci 1988; 33: 106–7PubMedCrossRefGoogle Scholar
  53. 53.
    Moody JP. Some aspects of the metabolism of tricyclic antidepressants. Postgrad Med J 1976; 52: 59–61PubMedGoogle Scholar
  54. 54.
    Javaid JI, Hendricks K, Davis JM. α1-Acid glycoprotein involvement in high affinity binding of tricyclic antidepressants to human plasma. Biochem Pharmacol 1983; 32: 1149–53PubMedCrossRefGoogle Scholar
  55. 55.
    Blye E, Lorch J, Cortell S. Extracorporeal therapy in the treatment of intoxication. Am J Kidney Dis 1984; 3: 321–38PubMedGoogle Scholar
  56. 56.
    Pond SM. Extracorporeal techniques in the treatment of poisoned patients. Med J Aust 1991; 154: 617–22PubMedGoogle Scholar
  57. 57.
    Sunshine P, Yaffe SJ. Amitriptyline poisoning: clinical and pathological findings in a fatal case. Am J Dis Child 1963; 106: 501–6PubMedGoogle Scholar
  58. 58.
    Oreopoulos DG, Lal S. Recovery from massive amitriptyline overdosage. Lancet 1968; II: 221CrossRefGoogle Scholar
  59. 59.
    Heath A, Delin K, Eden E, et al. Hemoperfusion with amberlite resin in the treatment of self-poisoning. Acta Med Scand 1980; 207: 455–60PubMedCrossRefGoogle Scholar
  60. 60.
    Pentel PR, Bullock ML, DeVane CL. Hemoperfusion for imipramine overdose: elimination of active metabolites. J Toxicol Clin Toxicol 1982; 19: 239–48PubMedCrossRefGoogle Scholar
  61. 61.
    Trafford JA, Jones RH, Evans R, et al. Haemoperfusion with R-004 amberlite resin for treating acute poisoning. BMJ 1977; 2: 1453–6PubMedCrossRefGoogle Scholar
  62. 62.
    Crome P, Volans GN, Hampel G, et al. Haemoperfusion in treatment of drug intoxication. BMJ 1978; 1: 174Google Scholar
  63. 63.
    Ryan III R, Wians Jr FH, Stigelman Jr WH, et al. Imipramine poisoning in a child: lack of efficacy of resin hemoperfusion. Pediatr Emerg Care 1985; 1: 201–4PubMedCrossRefGoogle Scholar
  64. 64.
    Heath A, Wickstrom I, Martensson E, et al. Treatment of antidepressant poisoning with resin hemoperfusion. Hum Toxicol 1982; 1: 361–71PubMedCrossRefGoogle Scholar
  65. 65.
    Diaz-Buxo JA, Farmer CD, Chandler JT. Hemoperfusion in the treatment of amitriptyline intoxication. Trans Am Soc Artif Intern Organs 1978; 24: 699–703PubMedGoogle Scholar
  66. 66.
    Iversen BM, Willassen YW, Bakke OM. Charcoal haemoperfusion in nortriptyline poisoning. Lancet 1978; I: 388–9CrossRefGoogle Scholar
  67. 67.
    Comstock TJ, Watson WA, Jennison TA. Severe amitriptyline intoxication and the use of charcoal hemoperfusion. Clin Pharm 1983; 2: 85–8PubMedGoogle Scholar
  68. 68.
    Engstrom JW, Young J, Rennie WA, et al. Noncardiogenic pulmonary edema after charcoal hemoperfusion. South Med J 1985; 78: 611–3PubMedCrossRefGoogle Scholar
  69. 69.
    Bismuth C, Conso F, Wattel F, et al. Coated activated charcoal hemoperfusion: experience of French anti-poison centers in 60 cases. Vet Hum Toxicol 1979; 21: 81–3PubMedGoogle Scholar
  70. 70.
    Haapanen EJ. Hemoperfusion in acute intoxication: clinical experience with 48 cases. Acta Med Scand 1982; 668: 76–81Google Scholar
  71. 71.
    Dönmez O, Cetinkaya M, Canbek R. Hemoperfusion in a child with amitriptyline intoxication. Pediatr Nephrol 2005; 20: 105–7PubMedCrossRefGoogle Scholar
  72. 72.
    Dawling S, Lynn K, Rosser R, et al. Nortriptyline metabolism in chronic renal failure: metabolite elimination. Clin Pharmacol Ther 1982; 32: 322–9PubMedCrossRefGoogle Scholar
  73. 73.
    Faulkner RD, Senekjian HO, Lee CS. Hemodialysis of doxepin and desmethyldoxepin in uremic patients. Artif Organs 1984; 8: 151–5PubMedCrossRefGoogle Scholar
  74. 74.
    Bailey PR, Sharman JR, O’Rourke J, et al. Haemodialysis and forced diuresis for tricyclic antidepressant poisoning. BMJ 1974; 4: 230–1PubMedCrossRefGoogle Scholar
  75. 75.
    Harthorne JW, Marcus AM, Kaye M. Management of massive imipramine overdosage with mannitol and artificial dialysis. N Engl J Med 1963; 268: 33–6PubMedCrossRefGoogle Scholar
  76. 76.
    De Broe ME, Verpooten BA, Van Haesebrouck B. Recent experience with prolonged hemoperfusion-hemodialysis treatment. Artif Organs 1979; 3: 188–90PubMedCrossRefGoogle Scholar
  77. 77.
    Durakovic Z, Plavsic F, Ivanovic D, et al. Resin hemoperfusion in the treatment of tricyclic antidepressant overdose. Artif Organs 1982; 6: 205–7PubMedCrossRefGoogle Scholar
  78. 78.
    Frank RD, Kierdorf HP. Is there a role for hemoperfusion/hemodialysis as a treatment option in severe tricyclic antidepressant intoxication? Int J Artif Organs 2000; 23: 618–23PubMedGoogle Scholar
  79. 79.
    Golper TA, Bennett WM. Drug removal by continuous arteriovenous haemofiltration: a review of the evidence in poisoned patients. Med Toxicol 1988; 3: 341–9CrossRefGoogle Scholar
  80. 80.
    Pentel PR, Scarlett W, Ross CA, et al. Reduction of desipramine cardiotoxicity and prolongation of survival in rats with the use of polyclonal drug-specific antibody Fab fragments. Ann Emerg Med 1995; 26: 334–41PubMedCrossRefGoogle Scholar
  81. 81.
    Dart RC, Sidki A, Sullivan Jr JB, et al. Ovine desipramine antibody fragments reverse desipramine cardiovascular toxicity in the rat. Ann Emerg Med 1996; 27: 309–15PubMedCrossRefGoogle Scholar
  82. 82.
    Keyler DE, Shelver WL, Landon J, et al. Toxicity of high doses of polyclonal drug-specific antibody Fab fragments. Int J Immunopharmacol 1994; 16: 1027–34PubMedCrossRefGoogle Scholar
  83. 83.
    Heard K, O’Malley GF, Dart RC. Treatment of amitriptyline poisoning with ovine antibody to tricyclic antidepressants. Lancet 1999; 354: 1614–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Paul I. Dargan
    • 1
  • Mark G. Colbridge
    • 1
  • Alison L. Jones
    • 1
  1. 1.National Poisons Information Service (London Centre)LondonUK
  2. 2.Guy’s & St Thomas’ NHS Foundation TrustNational Poisons Information Service (London Centre)LondonUK

Personalised recommendations