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Cyclic Antidepressants

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Critical Care Toxicology

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Abstract

The use of the cyclic antidepressants (CAs) in the treatment of major depression has decreased as newer and safer antidepressants have become available. Cyclic Antidepressants historically have been primarily used to treat major depression but are still prescribed for other psychiatric and medical conditions, such as chronic pain syndromes (e.g., fibromyalgia), peripheral neuropathy, nocturnal enuresis, migraine headache, selected drug withdrawal syndromes, and obsessive-compulsive, attention-deficit, panic and phobia, anxiety, and eating disorders [1, 2]. The CAs are associated with a low therapeutic index, potential severe cardiotoxicity in overdose, and a high frequency of adverse effects secondary to their nonspecific pharmacologic actions. Although CA use is less than it once was, the CAs remain on the 2014 American Association of Poison Control Centers’ list of Top 25 Categories of Substances associated with fatalities [1, 3].

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References

  1. Braithwaite RA. The tricyclic antidepressants. Contemp Issues Clin Biochem. 1985;3:211–39. Epub 1985/01/01.

    CAS  PubMed  Google Scholar 

  2. Reed C, Birnbaum HG, Ivanova JI, Schiller M, Waldman T, Mullen RE, et al. Real-world role of tricyclic antidepressants in the treatment of fibromyalgia. Pain Pract. 2012;12(7):533–40. Epub 2012/01/10.

    Article  PubMed  Google Scholar 

  3. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd annual report. Clin Toxicol (Phila). 2015;53(10):962–1147. Epub 2015/12/02.

    Article  CAS  Google Scholar 

  4. Foulke GE. Identifying toxicity risk early after antidepressant overdose. Am J Emerg Med. 1995;13(2):123–6. Epub 1995/03/01.

    Article  CAS  PubMed  Google Scholar 

  5. Battersby MW, O’Mahoney JJ, Beckwith AR, Hunt JL. Antidepressant deaths by overdose. Aust N Z J Psychiatry. 1996;30(2):223–8. Epub 1996/04/01.

    Article  CAS  PubMed  Google Scholar 

  6. Cassidy S, Henry J. Fatal toxicity of antidepressant drugs in overdose. Br Med J (Clin Res Ed). 1987;295(6605):1021–4. Epub 1987/10/24.

    Article  CAS  Google Scholar 

  7. Buckley NA, McManus PR. Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 1998;18(5):369–81. Epub 1998/05/20.

    Article  CAS  PubMed  Google Scholar 

  8. Mason J, Freemantle N, Eccles M. Fatal toxicity associated with antidepressant use in primary care. Br J Gen Pract. 2000;50(454):366–70. Epub 2000/07/18.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Jarvis MR. Clinical pharmacokinetics of tricyclic antidepressant overdose. Psychopharmacol Bull. 1991;27(4):541–50. Epub 1991/01/01.

    CAS  PubMed  Google Scholar 

  10. Preskorn SH. Pharmacokinetics of antidepressants: why and how they are relevant to treatment. J Clin Psychiatry. 1993;54(Suppl):14–34. discussion 55–6. Epub 1993/09/01.

    PubMed  Google Scholar 

  11. Haufroid V, Hantson P. CYP2D6 genetic polymorphisms and their relevance for poisoning due to amfetamines, opioid analgesics and antidepressants. Clin Toxicol (Phila). 2015;53(6):501–10. Epub 2015/05/23.

    Article  CAS  Google Scholar 

  12. Spiller HA, Winter ML, Mann KV, Borys DJ, Muir S, Krenzelok EP. Five-year multicenter retrospective review of cyclobenzaprine toxicity. J Emerg Med. 1995;13(6):781–5. Epub 1995/11/01.

    Article  CAS  PubMed  Google Scholar 

  13. Fleischman A, Chiang VW. Carbamazepine overdose recognized by a tricyclic antidepressant assay. Pediatrics. 2001;107(1):176–7. Epub 2001/01/03.

    Article  CAS  PubMed  Google Scholar 

  14. Yuan CM, Spandorfer PR, Miller SL, Henretig FM, Shaw LM. Evaluation of tricyclic antidepressant false positivity in a pediatric case of cyproheptadine (periactin) overdose. Ther Drug Monit. 2003;25(3):299–304. Epub 2003/05/27.

    Article  PubMed  Google Scholar 

  15. Matos ME, Burns MM, Shannon MW. False-positive tricyclic antidepressant drug screen results leading to the diagnosis of carbamazepine intoxication. Pediatrics. 2000;105(5), E66. Epub 2000/05/09.

    Article  CAS  PubMed  Google Scholar 

  16. Glauser J. Tricyclic antidepressant poisoning. Cleve Clin J Med. 2000;67(10):704–6, 9–13, 17–9. Epub 2000/11/04.

    Google Scholar 

  17. Pentel P, Peterson CD. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose. Ann Emerg Med. 1980;9(11):588–90. Epub 1980/11/01.

    Article  CAS  PubMed  Google Scholar 

  18. Newton EH, Shih RD, Hoffman RS. Cyclic antidepressant overdose: a review of current management strategies. Am J Emerg Med. 1994;12(3):376–9. Epub 1994/05/01.

    Article  CAS  PubMed  Google Scholar 

  19. Kolecki PF, Curry SC. Poisoning by sodium channel blocking agents. Crit Care Clin. 1997;13(4):829–48. Epub 1997/10/23.

    Article  CAS  PubMed  Google Scholar 

  20. Hoffman JR, Votey SR, Bayer M, Silver L. Effect of hypertonic sodium bicarbonate in the treatment of moderate-to-severe cyclic antidepressant overdose. Am J Emerg Med. 1993;11(4):336–41. Epub 1993/07/01.

    Article  CAS  PubMed  Google Scholar 

  21. 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. 1998;32(3 Pt 1):329–33. Epub 1998/09/16.

    Article  CAS  PubMed  Google Scholar 

  22. Phillips S, Brent J, Kulig K, Heiligenstein J, Birkett M. Fluoxetine versus tricyclic antidepressants: a prospective multicenter study of antidepressant drug overdoses. The Antidepressant Study Group. J Emerg Med. 1997;15(4):439–45. Epub 1997/07/01.

    Article  CAS  PubMed  Google Scholar 

  23. Ellison DW, Pentel PR. Clinical features and consequences of seizures due to cyclic antidepressant overdose. Am J Emerg Med. 1989;7(1):5–10. Epub 1989/01/01.

    Article  CAS  PubMed  Google Scholar 

  24. Merigian KS, Browning RG, Leeper KV. Successful treatment of amoxapine-induced refractory status epilepticus with propofol (diprivan). Acad Emerg Med. 1995;2(2):128–33. Epub 1995/02/01.

    Article  CAS  PubMed  Google Scholar 

  25. Crome P. Poisoning due to tricyclic antidepressant overdosage. Clinical presentation and treatment. Med Toxicol. 1986;1(4):261–85. Epub 1986/07/01.

    Article  CAS  PubMed  Google Scholar 

  26. Bolster M, Curran J, Busuttil A. A five year review of fatal self-ingested overdoses involving amitriptyline in Edinburgh 1983-’87. Hum Exp Toxicol. 1994;13(1):29–31. Epub 1994/01/01.

    Article  CAS  PubMed  Google Scholar 

  27. Henderson A, Wright M, Pond SM. Experience with 732 acute overdose patients admitted to an intensive care unit over six years. Med J Aust. 1993;158(1):28–30. Epub 1993/01/04.

    CAS  PubMed  Google Scholar 

  28. Foulke GE, Albertson TE, Walby WF. Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course. Am J Emerg Med. 1986;4(6):496–500. Epub 1986/11/01.

    Article  CAS  PubMed  Google Scholar 

  29. Caravati EM, Bossart PJ. Demographic and electrocardiographic factors associated with severe tricyclic antidepressant toxicity. J Toxicol Clin Toxicol. 1991;29(1):31–43. Epub 1991/01/01.

    Article  CAS  PubMed  Google Scholar 

  30. Hulten BA, Adams R, Askenasi R, Dallos V, Dawling S, Volans G, et al. Predicting severity of tricyclic antidepressant overdose. J Toxicol Clin Toxicol. 1992;30(2):161–70. Epub 1992/01/01.

    Article  CAS  PubMed  Google Scholar 

  31. Pounder DJ, Owen V, Quigley C. Postmortem changes in blood amitriptyline concentration. Am J Forensic Med Pathol. 1994;15(3):224–30. Epub 1994/09/01.

    Article  CAS  PubMed  Google Scholar 

  32. Hilberg T, Bugge A, Beylich KM, Ingum J, Bjorneboe A, Morland J. An animal model of postmortem amitriptyline redistribution. J Forensic Sci. 1993;38(1):81–90. Epub 1993/01/01.

    Article  CAS  PubMed  Google Scholar 

  33. Tokarski GF, Young MJ. Criteria for admitting patients with tricyclic antidepressant overdose. J Emerg Med. 1988;6(2):121–4. Epub 1988/03/01.

    Article  CAS  PubMed  Google Scholar 

  34. Shannon M, Merola J, Lovejoy Jr FH. Hypotension in severe tricyclic antidepressant overdose. Am J Emerg Med. 1988;6(5):439–42. Epub 1988/09/01.

    Article  CAS  PubMed  Google Scholar 

  35. Flaherty JJ, Cerva D, Graff J. ARDS associated with massive imipramine overdose. Am J Emerg Med. 1986;4(2):195–7. Epub 1986/03/01.

    Article  CAS  PubMed  Google Scholar 

  36. 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(2):195–201. Epub 1995/08/01.

    Article  CAS  PubMed  Google Scholar 

  37. 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(8):474–9. Epub 1985/08/22.

    Article  CAS  PubMed  Google Scholar 

  38. Niemann JT, Bessen HA, Rothstein RJ, Laks MM. Electrocardiographic criteria for tricyclic antidepressant cardiotoxicity. Am J Cardiol. 1986;57(13):1154–9. Epub 1986/05/01.

    Article  CAS  PubMed  Google Scholar 

  39. Vernon DD, Banner Jr 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. Epub 1991/04/01.

    Article  CAS  PubMed  Google Scholar 

  40. 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. Epub 1995/03/01.

    Article  CAS  PubMed  Google Scholar 

  41. Crome P, Dawling S, Braithwaite RA, Masters J, Walkey R. Effect of activated charcoal on absorption of nortriptyline. Lancet (London, England). 1977;2(8050):1203–5. Epub 1977/12/10.

    Article  CAS  Google Scholar 

  42. Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(3):203–33. Epub 2007/04/25.

    Article  CAS  Google Scholar 

  43. Adeva-Andany MM, Fernandez-Fernandez C, Mourino-Bayolo D, Castro-Quintela E, Dominguez-Montero A. Sodium bicarbonate therapy in patients with metabolic acidosis. Scientific World Journal. 2014;2014:627673. Epub 2014/11/19.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Cave G, Harvey MG. Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients? Critical Care (London, England). 2014;18(5):457. Epub 2015/02/13.

    Article  Google Scholar 

  45. Cave G, Harvey M, Graudins A. Intravenous lipid emulsion as antidote: a summary of published human experience. Emergency Medicine Australasia: EMA. 2011;23(2):123–41. Epub 2011/04/15.

    Article  PubMed  Google Scholar 

  46. Cave G, Harvey M, Shaw T, Damitz R, Chauhan A. Comparison of intravenous lipid emulsion, bicarbonate, and tailored liposomes in rabbit clomipramine toxicity. Acad Emerg Med. 2013;20(10):1076–9. Epub 2013/10/17.

    Article  PubMed  Google Scholar 

  47. Harvey M, Cave G, Ong B. Intravenous lipid emulsion-augmented plasma exchange in a rabbit model of clomipramine toxicity; survival, but no sink. Clin Toxicol (Phila). 2014;52(1):13–9. Epub 2014/01/09.

    Article  CAS  Google Scholar 

  48. Heinonen JA, Litonius E, Backman JT, Neuvonen PJ, Rosenberg PH. Intravenous lipid emulsion entraps amitriptyline into plasma and can lower its brain concentration–an experimental intoxication study in pigs. Basic Clin Pharmacol Toxicol. 2013;113(3):193–200. Epub 2013/05/04.

    Article  CAS  PubMed  Google Scholar 

  49. Teba L, Schiebel F, Dedhia HV, Lazzell VA. Beneficial effect of norepinephrine in the treatment of circulatory shock caused by tricyclic antidepressant overdose. Am J Emerg Med. 1988;6(6):566–8. Epub 1988/11/01.

    Article  CAS  PubMed  Google Scholar 

  50. 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. Epub 1997/09/26.

    Article  CAS  PubMed  Google Scholar 

  51. Williams JM, Hollingshed MJ, Vasilakis A, Morales M, Prescott JE, Graeber GM. Extracorporeal circulation in the management of severe tricyclic antidepressant overdose. Am J Emerg Med. 1994;12(4):456–8. Epub 1994/07/01.

    Article  CAS  PubMed  Google Scholar 

  52. Goodwin DA, Lally KP, Null Jr DM. Extracorporeal membrane oxygenation support for cardiac dysfunction from tricyclic antidepressant overdose. Crit Care Med. 1993;21(4):625–7. Epub 1993/04/01.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. New York City Poison Control Center, NY, USA

    Mark K. Su

  2. New York University School of Medicine, NY, USA

    Mark K. Su

Authors
  1. Mark K. Su
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Correspondence to Mark K. Su .

Editor information

Editors and Affiliations

  1. University of Colorado School of Medicine, Toxicology Associates, Denver, Colorado, USA

    Jeffrey Brent

  2. Office of New Drugs Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA

    Keith Burkhart

  3. Clinical Toxicology, St Thomas' Hospital, London, United Kingdom

    Paul Dargan

  4. University of Colorado School of Medicine, Toxicology Associates, Denver, Colorado, USA

    Benjamin Hatten

  5. Med & Toxicological Intensive Care Unit, Lariboisière Hospital Paris-Diderot University, Paris, France

    Bruno Megarbane

  6. University of Colorado School of Medicine, Toxicology Associates, Denver, Colorado, USA

    Robert Palmer

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

  1. I

    Evidence obtained from at least one properly randomized controlled trial.

  2. II-1

    Evidence obtained from well-designed controlled trials without randomization.

  3. II-2

    Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

  4. II-3

    Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

  5. III

    Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

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Su, M.K. (2016). Cyclic Antidepressants. In: Brent, J., Burkhart, K., Dargan, P., Hatten, B., Megarbane, B., Palmer, R. (eds) Critical Care Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-20790-2_92-1

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  • DOI: https://doi.org/10.1007/978-3-319-20790-2_92-1

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  • Online ISBN: 978-3-319-20790-2

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