Diagnosis and Management of Tricyclic Antidepressant Ingestion

  • Patrick George Minges
  • Robert W. ShafferEmail author


Tricyclic antidepressant (TCA) overdoses have become less common over the last 20 years as their overall use has decreased with the advent of safer and more effective antidepressants. Despite their declining popularity in the management of depression, they continue to be used clinically for conditions including the management of neuropathic and chronic pain, cyclic vomiting, nocturnal enuresis, OCD and ADHD. These medications continue to be a leading cause of mortality from intentional ingestions, and account for nearly half of all antidepressant-related deaths (Yates et al., Semin Dial 27(4):381–389, 2014). Common tricyclic antidepressants in use today include amitriptyline, nortriptyline, imipramine, desipramine and doxepin.

The management of tricyclic antidepressant poisonings can be quite challenging. Since they exert their toxicity through several different mechanisms an understanding of their pharmacology is imperative. TCAs all have inherent anticholinergic effects that may cause tachycardia, altered mental status and seizures. They can cause profound hypotension through alpha-adrenergic blockade as well as catecholamine depletion through reuptake inhibition. Finally, they block fast sodium channels in the cardiac conduction system leading to myocardial depression and ventricular arrhythmias (Agrawal et al., J Emerg Med 34(3):321–325, 2008).

Successful treatment of patients poisoned by tricyclic antidepressants hinges on prompt diagnosis and recognition of the classic EKG findings associated with their toxicity. GI decontamination should be considered when patients present within the first 1–2 h following an overdose. Serum alkalinization with sodium bicarbonate is considered the first-line treatment when signs of cardiotoxicity develop. Patients with refractory hypotension may require vasopressor support.


Overdose Toxicology Tricyclic antidepressant Cyclic antidepressant Overdose Sodium bicarbonate Seizure Arrhythmia Ventricular tachycardia QRS interval Hypotension Intralipid Magnesium sulfate Lidocaine Hypertonic saline Amitriptyline Nortriptyline 


  1. 1.
    Agrawal P, Nadel ES, Brown DF. Tricyclic antidepressant overdose. J Emerg Med. 2008;34(3):321–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Yates C, Galvao T, Sowinski KM, et al. Extracorporeal treatment for tricyclic antidepressant poisoning: recommendations from the EXTRIP Workgroup. Semin Dial. 2014;27(4):381–9.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Harrigan RA, Brady RJ. ECG abnormalities in tricyclic antidepressant ingestion. Am J Emerg Med. 1999;17(4):387–93.PubMedCrossRefGoogle Scholar
  4. 4.
    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. 1985;313(8):474–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Wolfe TR, Caravati EM, Rollins DE. Terminal 40-ms frontal place axis as a marker for tricyclic antidepressant overdose. Ann Emerg Med. 1989;18:348–51.PubMedCrossRefGoogle Scholar
  6. 6.
    Karkkainen S, Neuvonen PJ. Pharmacokinetics of amitriptyline influenced by oral charcoal and urine pH. Int J Clin Pharmacol Ther Toxicol. 1986;24:326–32.PubMedGoogle Scholar
  7. 7.
    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(3):187–94.PubMedCrossRefGoogle Scholar
  8. 8.
    Bosse GM, Barefoot JA, Pfeifer MP, Rodgers GC. Comparison of three methods of gut decontamination in tricyclic antidepressant overdose. J Emerg Med. 1995;13(2):203–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Sasyniuk BI, Jhamandas V, Valois M. Experimental amitriptyline intoxication: treatment of cardiac toxicity with sodium bicarbonate. Ann Emerg Med. 1986;15(9):1052–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Blackman K, Brown SF, Wilkes GJ. Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emerg Med. 2001;13:204–10.CrossRefGoogle Scholar
  11. 11.
    Hoffman JR, McElroy CR. Bicarbonate therapy for dysrhythmia and hypotension in tricyclic antidepressant overdose. West J Med. 1981;134(1):60–4.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Vernon DD, Banner W, Garrett JS, Dean JM. Efficacy of dopamine and norepinephrine for treatment of hemodynamic compromise in amitriptyline intoxication. Crit Care Med. 1991;19(4):544–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Tran TP, Panacek EA, Rhee KJ, Foulke GE. Response to dopamine vs norepinephrine in tricyclic antidepressant-induced hypotension. Acad Emerg Med. 1997;4(9):864–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Barry JD, Durkovich DW, Williams SR. Vasopressin treatment for cyclic antidepressant overdose. J Emerg Med. 2006;31(1):65–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Ellison DW, Pentel PR. Clinical Features and consequences of seizures due to cyclic antidepressant overdose. Am J Med. 1989;7(1):5–10.Google Scholar
  16. 16.
    Merigian KS, Browning RG, Leeper KV. Successful treatment of amoxapine-induced refractory status epilepticus with propofol. Acad Emerg Med. 1995;2(2):128–33.PubMedCrossRefGoogle Scholar
  17. 17.
    Ozcon MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med. 2014;29(2):59–70.CrossRefGoogle Scholar
  18. 18.
    Varney SM, Bebarta VS, Vargas TE, Boudreau S, Castaneda M. Intravenous lipid emulsion therapy does not improve hypotension compared to sodium bicarbonate for tricyclic antidepressant toxicity: a randomized, controlled pilot study in a swine model. Acad Emerg Med. 2014;21(11):1212–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Ann Emerg Med. 2007;49(2):178–85.PubMedCrossRefGoogle Scholar
  20. 20.
    Litonius E, Niiya T, Neuvonen PJ, Rosenberg PH. No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline. Basic Clin Pharmacol Toxicol. 2012;110(4):378–83.PubMedCrossRefGoogle Scholar
  21. 21.
    Blaber MS, Khan JN, Brebner JA, Mccolm R. “Lipid rescue” for tricyclic antidepressant cardiotoxicity. J Emerg Med. 2012;43(3):465–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kiberd MB, Minor SF. Lipid therapy for the treatment of a refractory amitriptyline overdose. CJEM. 2012;14(3):193–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Agarwala R, Ahmed SZ, Wiegand TJ. Prolonged use of intravenous lipid emulsion in a severe tricyclic antidepressant overdose. J Med Toxicol. 2014;10:210–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Engels PT, Davidow JS. Intravenous fat emulsion to reverse haemodynamic instability from intentional amitriptyline overdose. Resuscitation. 2010;81(8):1037–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Weinberg GL. Lipid emulsion infusion: resuscitation for local anesthetic and other drug overdose. Anesthesiology. 2012;117(1):180–7.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    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. 1996;32(3):329–33.CrossRefGoogle Scholar
  27. 27.
    Mckinney PE, Rasmussen R. Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline. Ann Emerg Med. 2003;42(1):20–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Foianini A, Weigand TJ, Benowitz N. What is the role of lidocaine or phenytoin in tricyclic antidepressant-induced cardiotoxicity. Clin Toxicol. 2010;48(4):325–30.CrossRefGoogle Scholar
  29. 29.
    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. 1994;22(3):494–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning—management of arrhythmias. Med Toxicol. 1986;1:101–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Emamhadi M, Mostafazadeh B, Hassanijirdehi M. Tricyclic antidepressant poisoning treated by magnesium sulfate: a randomized, clinical trial. Drug Chem Toxicol. 2012;35(3):300–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Sarisoy O, Babaoglu K, Tukay S, et al. Effect of magnesium sulfate for treatment of ventricular tachycardia in amytriptyline intoxication. Pediatr Emerg Care. 2007;23:646–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Knudsen K, Abrahamsson K. Magnesium sulfate in the treatment of ventricular fibrillation in amitriptyline poisoning. Eur Heart J. 1997;18(5):881.PubMedCrossRefGoogle Scholar
  34. 34.
    Arens AM, Kearney T. Adverse effects of physostigmine. J Med Toxicol. 2019;15:184–91. Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Emergency MedicineUniversity of Michigan HospitalsAnn ArborUSA
  2. 2.Department of Emergency MedicineUniversity of Michigan Health SystemAnn ArborUSA

Personalised recommendations