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Serotonergic Antidepressants

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Critical Care Toxicology

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Abstract

While many drugs have some effect on serotonergic receptors this chapter focuses upon the toxicity seen with medications whose primary antidepressant therapeutic mechanism of action is to modify serotoninergic transmission. This includes selective serotonin reuptake inhibitors (SSRI), serotonin noradrenergic reuptake inhibitors (SNRI), and tetracyclic and triazolopyridine antidepressants (Tables 1, 2, 3, and 4).

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References

  1. Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev. 1992;72(1):165–229.

    CAS  PubMed  Google Scholar 

  2. Wang H, Goehring A, Wang KH, Penmatsa A, Ressler R, Gouaux E. Structural basis for action by diverse antidepressants on biogenic amine transporters. Nature. 2013;503(7474):141–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kent JM. SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression. Lancet. 2000;355(9207):911–8.

    Article  CAS  PubMed  Google Scholar 

  4. Buckley NA, Whyte IM, Dawson AH, Isbister GK. A prospective cohort study of trends in self-poisoning, newcastle, australia, 1987–2012: Plus ça change, plus c'est la même chose. Med J Aust. 2015;202(8):438–42.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. Buckley NA, McManus PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of united kingdom mortality data. BMJ. 2002;325(7376):1332–3.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hawton K, Bergen H, Simkin S, Cooper J, Waters K, Gunnell D, Kapur N. Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose. Br J Psychiatry. 2010;196(5):354–8.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Koski A, Vuori E, Ojanperä I. Newer antidepressants: evaluation of fatal toxicity index and interaction with alcohol based on finnish postmortem data. Int J Leg Med. 2005;119(6):344–8.

    Article  Google Scholar 

  9. Whyte I. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003;96(5):369–74.

    Article  CAS  PubMed  Google Scholar 

  10. Hiemke C, Härtter S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther. 2000;85(1):11–28.

    Article  CAS  PubMed  Google Scholar 

  11. Fujishiro J, Imanishi T, Onozawa K, Tsushima M. Comparison of the anticholinergic effects of the serotonergic antidepressants, paroxetine, fluvoxamine and clomipramine. Eur J Pharmacol. 2002;454(2):183–8.

    Article  CAS  PubMed  Google Scholar 

  12. White NC, Litovitz T, Clancy C. Suicidal antidepressant overdoses: a comparative analysis by antidepressant type. J Med Toxicol. 2008;4(4):238–50.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rajamani S, Eckhardt LL, Valdivia CR, Klemens CA, Gillman BM, Anderson CL, et al. Drug-induced long QT syndrome: HERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br J Pharmacol. 2006;149(5):481–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (ssris) in overdose. J Toxicol Clin Toxicol. 2004;42(3):277–85.

    Article  CAS  PubMed  Google Scholar 

  15. Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626.

    Article  PubMed  Google Scholar 

  16. Friberg LE, Isbister GK, Hackett LP, Duffull SB. The population pharmacokinetics of citalopram after deliberate self-poisoning: a bayesian approach. J Pharmacokinet Pharmacodyn. 2005;32(3–4):571–605.

    Article  CAS  PubMed  Google Scholar 

  17. Friberg LE, Isbister GK, Duffull SB. Pharmacokinetic-pharmacodynamic modelling of QT interval prolongation following citalopram overdoses. Br J Clin Pharmacol. 2006;61(2):177–90.

    Article  CAS  PubMed  Google Scholar 

  18. Isbister GK, Friberg LE, Duffull SB. Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose. Intensive Care Med. 2006;32(7):1060–5.

    Article  CAS  PubMed  Google Scholar 

  19. van Gorp F, Whyte IM, Isbister GK. Clinical and ECG effects of escitalopram overdose. Ann Emerg Med. 2009;54(3):404–8.

    Article  PubMed  Google Scholar 

  20. van Gorp F, Duffull S, Hackett LP, Isbister GK. Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal. Br J Clin Pharmacol. 2012;73(3):402–10.

    Article  PubMed  Google Scholar 

  21. Hayes BD, Klein-Schwartz W, Clark RF, Muller AA, Miloradovich JE. Comparison of toxicity of acute overdoses with citalopram and escitalopram. J Emerg Med. 2010;39(1):44–8.

    Article  PubMed  Google Scholar 

  22. Isbister GK, Friberg LE, Stokes B, Buckley NA, Lee C, Gunja N, et al. Activated charcoal decreases the risk of QT prolongation after citalopram overdose. Ann Emerg Med. 2007;50(5):593–600, 600.e1–46.

    Article  PubMed  Google Scholar 

  23. Tarabar AF, Hoffman RS, Nelson LS. Citalopram overdose: late presentation of torsades de pointes (tdp) with cardiac arrest. J Med Toxicol. 2008;4(2):101–5.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kanjanauthai S, Kanluen T, Chareonthaitawee P. Citalopram induced torsade de pointes, a rare life threatening side effect. Int J Cardiol. 2008;131(1):e33–4.

    Article  PubMed  Google Scholar 

  25. White S, Rumack B. The acetaminophen toxicity equations: “solutions” for acetaminophen toxicity based on the rumack-matthew nomogram. Ann Emerg Med. 2005;45(5):563–4.

    Article  PubMed  Google Scholar 

  26. Chan A, Isbister G, Kirkpatrick C, Dufful S. QJM drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram. QJM. 2007;100(10):609–15.

    Article  CAS  PubMed  Google Scholar 

  27. Waring WS, Graham A, Gray J, Wilson AD, Howell C, Bateman DN. Evaluation of a QT nomogram for risk assessment after antidepressant overdose. Br J Clin Pharmacol. 2010;70(6):881–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635–42.

    Article  CAS  PubMed  Google Scholar 

  29. Thomas SH, Behr ER. Pharmacological treatment of acquired QT prolongation and torsades de pointes. British journal of clinical pharmacology. 2016;81(3):420–7.

    Google Scholar 

  30. Kumar VV, Oscarsson S, Friberg LE, Isbister GK, Hackett LP, Duffull SB. The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose. Clin Pharmacol Ther. 2009;86(4):403–10.

    Article  CAS  PubMed  Google Scholar 

  31. Chan AN, Gunja N, Ryan CJ. A comparison of venlafaxine and ssris in deliberate self-poisoning. J Med Toxicol. 2010;6(2):116–21.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. QJM. 2003;96(5):369–74.

    Article  CAS  PubMed  Google Scholar 

  33. Wang S-Y, Calderon J, Wang GK. Block of neuronal na + channels by antidepressant duloxetine in a state-dependent manner. J Am Soc Anesthesiol. 2010;113(3):655–65.

    CAS  Google Scholar 

  34. Khalifa M, Daleau P, Turgeon J. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther. 1999;291(1):280–4.

    CAS  PubMed  Google Scholar 

  35. Howell C, Wilson AD, Waring WS. Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235 consecutive cases. Br J Clin Pharmacol. 2007;64(2):192–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Batista M, Dugernier T, Simon M, Haufroid V, Capron A, Fonseca S, et al. The spectrum of acute heart failure after venlafaxine overdose. Clin Toxicol (Phila). 2013;51(2):92–5.

    Article  CAS  Google Scholar 

  37. Neil CJ, Chong CR, Nguyen TH, Horowitz JD. Occurrence of tako-tsubo cardiomyopathy in association with ingestion of serotonin/noradrenaline reuptake inhibitors. Heart Lung Circ. 2012;21(4):203–5.

    Article  CAS  PubMed  Google Scholar 

  38. Christoph M, Ebner B, Stolte D, Ibrahim K, Kolschmann S, Strasser RH, Schön S. Broken heart syndrome: Tako tsubo cardiomyopathy associated with an overdose of the serotonin-norepinephrine reuptake inhibitor venlafaxine. Eur Neuropsychopharmacol. 2010;20(8):594–7.

    Article  CAS  PubMed  Google Scholar 

  39. Francino MC, Bretaudeau Deguigne M, Badin J, Turcant A, Perrotin D. Hypoglycaemia: a little known effect of venlafaxine overdose. Clin Toxicol (Phila). 2012;50(3):215–7.

    Article  CAS  Google Scholar 

  40. Jacob J, Albert D, Heard K. Single-agent duloxetine ingestions. Hum Exp Toxicol. 2013;32(4):427–33.

    Article  CAS  PubMed  Google Scholar 

  41. Just S, Gros S, Reichert C, Heistermann E, Hofmann- Walbeck P, Stedtler U, et al. Duloxetine overdose: a case series Clinical Toxicology. 2015;53(4):387.

    Google Scholar 

  42. Höjer J, Hulting J, Salmonson H. Fatal cardiotoxicity induced by venlafaxine overdosage. Clin Toxicol (Phila). 2008;46(4):336–7.

    Article  Google Scholar 

  43. Bosse GM, Spiller HA, Collins AM. A fatal case of venlafaxine overdose. J Med Toxicol. 2008;4(1):18–20.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Wilson AD, Howell C, Waring WS. Venlafaxine ingestion is associated with rhabdomyolysis in adults: a case series. J Toxicol Sci. 2007;32(1):97–101.

    Article  CAS  PubMed  Google Scholar 

  45. Holliday SM, Benfield P. Venlafaxine. Drugs. 1995;49(2):280–94.

    Article  CAS  PubMed  Google Scholar 

  46. Kumar VV, Isbister GK, Duffull SB. The effect of decontamination procedures on the pharmacodynamics of venlafaxine in overdose. Br J Clin Pharmacol. 2011;72(1):125–32.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Isbister GK. Electrocardiogram changes and arrhythmias in venlafaxine overdose. Br J Clin Pharmacol. 2009;9999(999A):572–6.

    Article  Google Scholar 

  48. Vinetti M, Haufroid V, Capron A, Classen J-FO, Marchandise S, Hantson P. Severe acute cardiomyopathy associated with venlafaxine overdose and possible role of CYP2D6 and CYP2C19 polymorphisms. Clin Toxicol (Phila). 2011;49(9):865–9.

    Article  CAS  Google Scholar 

  49. Hjer J, Hulting J, Salmonson H. Fatal cardiotoxicity induced by venlafaxine overdosage. Clin Toxicol (Phila). 2008;46(4):336–7.

    Article  Google Scholar 

  50. Samuelov-Kinori L, Kinori M, Kogan Y, Swartzon M, Shalev H, Guy D, et al. Takotsubo cardiomyopathy and QT interval prolongation: who are the patients at risk for torsades de pointes? J Electrocardiol. 2009;42(4):353–7.

    Article  PubMed  Google Scholar 

  51. Combes A, Peytavin G, Théron D. Conduction disturbances associated with venlafaxine. Ann Intern Med. 2001;134(2):166.

    Article  CAS  PubMed  Google Scholar 

  52. Shah AS, Eddleston M. Should phenytoin or barbiturates be used as second-line anticonvulsant therapy for toxicological seizures? Clinical Toxicology. 2010;48(8):800–5.

    Google Scholar 

  53. Gillman PK. A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status. Hum Psychopharmacol Clin Exp. 2006;21(2):117–25.

    Article  CAS  Google Scholar 

  54. Timmer CJ, Sitsen JMA, Delbressine LP. Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet. 2000;38(6):461–74.

    Article  CAS  PubMed  Google Scholar 

  55. Berling I, Isbister GK. Mirtazapine overdose is unlikely to cause major toxicity. Clin Toxicol. 2014;52(1):20–4.

    Article  CAS  Google Scholar 

  56. LoVecchio F, Riley B, Pizon A, Brown M. Outcomes after isolated mirtazapine (remeront) supratherapeutic ingestions. J Emerg Med. 2008;34(1):77–8.

    Article  PubMed  Google Scholar 

  57. Stephen Waring W, Good AM, Nicholas Bateman D. Lack of significant toxicity after mirtazapine overdose: a five-year review of cases admitted to a regional toxicology unit. Clin Toxicol (Phila). 2007;45(1):45–50.

    Article  Google Scholar 

  58. Schaper A, Farber E, Ebbecke M, Desel H. Suicide with mirtazapine-hardly possible. J Toxicol Clin Toxicol. 2002;40(3):343–4.

    Google Scholar 

  59. Koseoglu Z, Kara B, Satar S. Bradycardia and hypotension in mianserin intoxication. Human & experimental toxicology. 2010; 29(10):887–8.

    Google Scholar 

  60. Haefeli WE, Schoenenberger RA, Scholer A. Recurrent ventricular fibrillation in mianserin intoxication. BMJ Br Med J. 1991;302(6773):415.

    Article  CAS  Google Scholar 

  61. Hla KK, Boyd O. Mianserin and complete heart block. Hum Exp Toxicol. 1987;6(5):401–2.

    Article  CAS  Google Scholar 

  62. Chand S, Crome P, Dawling S. One hundred cases of acute intoxication with mianserin hydrochloride. Pharmacopsychiatry. 1981;14(01):15–7.

    Article  Google Scholar 

  63. Shaw WL. The comparative safety of mianserin in overdose. Curr Med Res Opin. 1980;6 Suppl 7:44–51.

    Article  Google Scholar 

  64. Inman WW. Blood disorders and suicide in patients taking mianserin or amitriptyline. Lancet. 1988;332(8602):90–2.

    Article  Google Scholar 

  65. Brogden RN, Heel RC, Speight TM, Avery GS. Trazodone: a review of its pharmacological properties and therapeutic use in depression and anxiety. Drugs. 1981;21(6):401–29.

    Article  CAS  PubMed  Google Scholar 

  66. Haria M, Fitton A, McTavish D. Trazodone. Drugs Aging. 1994;4(4):331–55.

    Article  CAS  PubMed  Google Scholar 

  67. Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006;34 Suppl 1:D668–72.

    Article  CAS  PubMed  Google Scholar 

  68. Buckley DNA, McManus PR. Can the fatal toxicity of antidepressant drugs be predicted with pharmacological and toxicological data? Drug Saf. 2012;18(5):369–81.

    Article  Google Scholar 

  69. Rhyee SH, Farrugia L, Campleman SL, Wax PM, Brent J, Toxicology Investigators Consortium. The toxicology investigators consortium case registry – the 2014 experience. J Med Toxicol. 2015;11(4):388–409.

    Article  CAS  PubMed  Google Scholar 

  70. Henry JA, Ali CJ. Trazodone overdosage: experience from a poisons information service. Hum Exp Toxicol. 1983;2(2):353–6.

    Article  CAS  Google Scholar 

  71. Chung KJ, Wang YC, Liu BM, Supernaw RB. Management of ventricular dysrhythmia secondary to trazodone overdose. J Emerg Med. 2008;35(2):171–4.

    Article  PubMed  Google Scholar 

  72. Service JA, Waring WS. QT prolongation and delayed atrioventricular conduction caused by acute ingestion of trazodone. Clin Toxicol (Phila). 2008;46(1):71–3.

    Article  CAS  Google Scholar 

  73. Perry R, Cassagnol M. Desvenlafaxine: a new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder. Clin Ther. 2009;31(Pt 1):1374–404.

    Article  CAS  PubMed  Google Scholar 

  74. Deepak P, Kumar TN. Duloxetine-pharmacological aspects. Int J Biol Med Res. 2011;2(2):589–92.

    Google Scholar 

  75. Knadler MP, Lobo E, Chappell J, Bergstrom R. Duloxetine. Clin Pharmacokinet. 2011;50(5):281–94.

    Article  CAS  PubMed  Google Scholar 

  76. Shami M, Elliott HL, Kelman AW, Whiting B. The pharmacokinetics of mianserin. Br J Clin Pharmacol. 1983;15(S2):313S–22.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Katona CL, Katona CP. New generation multi-modal antidepressants: focus on vortioxetine for major depressive disorder. Neuropsychiatr Dis Treat. 2014;10:349–54.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Areberg J, Søgaard B, Højer AM. The clinical pharmacokinetics of lu AA21004 and its major metabolite in healthy young volunteers. Basic Clin Pharmacol Toxicol. 2012;111(3):198–205.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

    Andrew H. Dawson

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  1. Andrew H. Dawson
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Correspondence to Andrew H. Dawson .

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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Dawson, A.H. (2016). Serotonergic 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_36-1

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  • DOI: https://doi.org/10.1007/978-3-319-20790-2_36-1

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