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Antidepressant Toxicity and the Need for Identification and Concentration Monitoring in Overdose

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  • Drug Concentration Monitoring
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Summary

Antidepressant drugs are among the most commonly encountered causes of self-poisoning. These drugs include tricyclics, tetracyclics, bicyclics and mono-cyclics, as well as monoamine oxidase (MAO) inhibitors and selective serotonin reuptake inhibitors (SSRIs). Of these, the tricyclic antidepressants (TCAs) are generally more toxic in overdose, with major toxicity usually manifesting within the first 6 hours after overdose.

Various studies indicate that patients at risk of toxicity from TCA overdose may be identified by neurological, cardiovascular and electrocardiography status, together with a quantitative estimate of the plasma drug concentration. While there are various methods available for such chemical estimations, the most satisfactory appears to be fluorescence polarisation immunoassay which gives rapid quantitative results for a variety of TCAs.

The selective MAO-A inhibitor antidepressants and the SSRIs are relatively nontoxic when taken alone. However, overdoses of combinations of MAO inhibitors and either SSRIs or TCAs with serotonin reuptake blocking activity may result in a serotonin syndrome with a severe or fatal outcome. Features of this syndrome include hyperpyrexia, disseminated intravascular coagulation, convulsions, coma and muscle rigidity, which may not develop until 6 to 12 hours after overdose. While qualitative chemical identification of these drugs following overdose is helpful in confirming the diagnosis, it is not mandatory. The increasing use of MAO-A inhibitors and SSRIs in the treatment of depression suggests that careful clinical observation is required when combination overdoses are suspected.

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References

  1. Guze SB, Robins E. Suicide among primary affective disorders. Br J Psychiatr 1970; 117: 437–8

    CAS  Google Scholar 

  2. Hagnell O, Lanke J, Rorsman B. Suicide rates in the Lundby study; mental illness as a risk factor for suicide. Neuropsychobiology 1981; 7: 248–53

    PubMed  CAS  Google Scholar 

  3. Meredith TJ. Epidemiology of poisoning. Pharmacol Ther 1993; 59: 251–6

    PubMed  CAS  Google Scholar 

  4. Welcher B, Rubin P, Nordentoft M. Admission of self-poisoned patients during one year at the Poisoning Treatment Centre, Copenhagen, Denmark. Acta Psychiatr Scand 1993; Suppl. 371: 38–44

    Google Scholar 

  5. 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: 28–30

    PubMed  CAS  Google Scholar 

  6. Rettersol N. Death due to overdose of antidepressants; experiences from Norway. Acta Psychiatr Scand 1993; Suppl. 371: 28–32

    Google Scholar 

  7. McGrath J. A survey of deliberate self-poisoning. Med J Aust 1989; 150: 317–22

    PubMed  CAS  Google Scholar 

  8. Crome P. The toxicity of drugs used for suicide. Acta Psychiatr Scand 1993; Suppl. 371: 33–7

    Google Scholar 

  9. Teige B, Fleischer E. Medikament — og alkoholdodsfall undersokt ved Rettsmedisinsk institutt, Universitetet I Oslo, I arene 1977–1979. Tidsskr Nor Laegeforen 1981; 101: 1563–6

    PubMed  CAS  Google Scholar 

  10. Starkey IR, Lawson AAH. Poisoning with tricyclic and related antidepressants — a ten-year review. Q J Med 1980; NS49: 33–49

    PubMed  CAS  Google Scholar 

  11. Crome P. Antidepressant overdosage. Drugs 1982; 23: 431–61

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  15. Montgomery SA, Baldwin D, Green M. Why do amitriptyline and dothiepin appear to be so dangerous in overdose? Acta Psychiatr Scand 1989; Suppl. 354: 47–53

    Google Scholar 

  16. Reid F, Henry JA. Lofepramine overdosage. Pharmacopsychiatry 1990; 23: 23–7

    PubMed  Google Scholar 

  17. Cassidy S, Henry J. Fatal toxicity of antidepressant drugs in overdose. BMJ 1987; 295: 1021–4

    PubMed  CAS  Google Scholar 

  18. Litovitz TL, Bailey KM, Schmitz BF, et al. 1990 Annual Report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1991; 9: 461–509

    PubMed  CAS  Google Scholar 

  19. Litovitz TL, Schmitz BF, Bailey KM. 1989 Annual Report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med 1990; 8: 394–442

    PubMed  CAS  Google Scholar 

  20. Kapur S, Mieczkowski T, Mann JJ. Antidepressant medications and the relative risk of suicide attempt and suicide. JAMA 1992; 268: 3441–5

    PubMed  CAS  Google Scholar 

  21. Farmer RDT, Pinder RM. Why do fatal overdose rates vary between antidepressants? Acta Psychiat Scand 1989; 80 Suppl. 354: 25–35

    Google Scholar 

  22. Alsen M, Ekedahl A, Lowenhielm P, et al. Medicine self-poisoning and the sources of the drugs in Lund, Sweden. Acta Psychiat Scand 1994; 89: 255–61

    PubMed  CAS  Google Scholar 

  23. Vuori E, Ruohonen A, Penttila A, et al. Fatal poisonings with antidepressants in Finland 1985–1987. Acta Psychiat Scand 1989; 80 Suppl. 354: 55–60

    Google Scholar 

  24. Wedin GP, Oderda G, Klein-Schwartz W, et al. Relative toxicity of cyclic antidepressants. Ann Emerg Med 1986; 14: 797–804

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Geltzer J. Limits to chemotherapy of depression. Psychopathology 1986; 19: 108–17

    Google Scholar 

  27. Chand S, Crome P, Dawlins S. One hundred cases of intoxication with mianserin hydrochloride. Pharmacopsychiatry 1981; 14: 15–7

    Google Scholar 

  28. Inman WHW. Blood disorders and suicide in patients taking minaserin or amitriptyline. Lancet 1988; 2: 90–2

    PubMed  CAS  Google Scholar 

  29. Gamble DE, Peterson LG. Trazodone overdose: four years of experience from voluntary reports. J Clin Psychiatry 1986; 47: 544–6

    PubMed  CAS  Google Scholar 

  30. Knudsen K, Heath A. Effects of self poisoning with maprotiline. BMJ 1984; 288: 601–3

    PubMed  CAS  Google Scholar 

  31. Park J, Proudfoot AP. Acute poisoning with maprotiline hydrochloride. BMJ 1977; 1: 1573

    PubMed  CAS  Google Scholar 

  32. Edwards JG. Antidepressants and convulsions. Lancet 1979; 2: 1368–9

    PubMed  CAS  Google Scholar 

  33. Davidson J. Seizures and bupropion: a review. J Clin Psychiatr 1989; 50: 256–61

    CAS  Google Scholar 

  34. Spiller HA, Ramoska EA, Krenzelok EP, et al. Bupropion overdose: a 3-year multi-center retrospective analysis. Am J EmergMed 1994; 12: 43–5

    CAS  Google Scholar 

  35. Kulig K, Rumack BH, Sullivan JB, et al. Amoxapine overdose: coma and seizures without cardiotoxic effects. JAMA 1982; 248: 1092–4

    PubMed  CAS  Google Scholar 

  36. Litovitz TL, Troutman WG. Amoxapine overdose. Seizures and fatalities. JAMA 1983; 250: 1069–71

    PubMed  CAS  Google Scholar 

  37. de Jonghe F, Swinkels JA. The safety of antidepressants. Drugs 1992; 43 Suppl. 2: 40–7

    PubMed  Google Scholar 

  38. Molcho A, Stanley M. Antidepressants and suicide risk: issues of chemical and behavioural toxicity. J Clin Psychopharmacol 1992; 12: 13S–18S

    PubMed  CAS  Google Scholar 

  39. Linden CH, Rumack BH, Strehlke C. Monoamine oxidase inhibitor overdose. Ann Emerg Med 1984; 13: 1137–44

    PubMed  CAS  Google Scholar 

  40. Davis JM, Bartlett E, Termini BA. Overdosage of psychotropic drugs: a review, Part II: Antidepressants and other psychotropic agents. Dis Nerv System 1968, 29: 246–56

    CAS  Google Scholar 

  41. Henry JA. Toxicity of antidepressants; comparisons with fluoxetine. Int Clin Psychopharmacol 1992; 6 Suppl. 6: 22–7

    PubMed  Google Scholar 

  42. Henry JA. A fatal toxicity index for antidepressant poisoning. Acta Psychiatr Scand 1989; 80 Suppl. 354: 37–45

    Google Scholar 

  43. Sternbach H. The serotonin syndrome. Am J Psychiatr 1991; 148: 705–13

    PubMed  CAS  Google Scholar 

  44. Tackley RM, Tregaskis B. Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction. Anaesthesia 1987; 42: 760–3

    PubMed  CAS  Google Scholar 

  45. Tiller JW. Clinical overview on moclobemide. Progr Neuropsychopharmacol Biol Psychiatr 1993; 17: 703–12

    CAS  Google Scholar 

  46. Mayersohn M, Guentert TW. Clinical pharmacokinetics of the monamine oxide-A inhibitor moclobemide. Clin Pharmacokinet 1995; 29: in press

  47. Hackett LP, Joyce DA, Hall RW, et al. Disposition and clinical effects of moclobemide and three of its metabolites following overdose. Drug Invest 1993; 5: 281–4

    Google Scholar 

  48. Moll E, Hetzel W. Moclobemide (RO 11–1163) safety in depressed patients. Acta Psychiatr Scand 1990; 360 Suppl.: 69–70

    CAS  Google Scholar 

  49. Hetzel W. Safety of moclobemide taken in overdose for attempted suicide. Psychopharmacology 1992; 106: S127–9

    PubMed  Google Scholar 

  50. Myrenfors PG, Eriksson T, Sandsted CS, et al. Moclobemide overdose. J Intern Med 1993; 233: 113–5

    PubMed  CAS  Google Scholar 

  51. Vine R, Norman TR, Burrows GD. A case of moclobemide overdose. Int Clin Psychopharmacol 1988; 3: 325–6

    PubMed  CAS  Google Scholar 

  52. Azoyan P, Garnier R, Baud FJ, et al. Intoxication aigue par la toloxatone. Therapie 1990; 45: 139–44

    PubMed  CAS  Google Scholar 

  53. Power BM, Pinder M, Hackett LP, et al. Fatal serotonin syndrome following a combined overdose of moclobemide, clomipramine and fluoxetine. Anaesth Intensive Care 1995; 23: 499–502

    PubMed  CAS  Google Scholar 

  54. Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdose. Lancet 1993; 342: 1419

    PubMed  CAS  Google Scholar 

  55. Brodribb TR, Downey M, Gilbar PJ. Efficacy and adverse effects of moclobemide. Lancet 1994; 343: 475

    PubMed  CAS  Google Scholar 

  56. Leonard BE. Toxicity of antidepressants in overdose. Int J Clin Pharmacol Res 1989; 9: 101–10

    PubMed  CAS  Google Scholar 

  57. Tollefson GD. Antidepressant treatment and side effect considerations. J Clin Psychiatr 1991; 52 Suppl.: 4–13

    Google Scholar 

  58. Nemeroff CB. Paroxetine: an overview of the efficacy and safety of a new selective serotonin reuptake inhibitor in the treatment of depression. J Clin Psychopharmacol 1993; 13 (6 Suppl. 2): 10S–17S

    PubMed  CAS  Google Scholar 

  59. Nemeroff CB. The clinical pharmacology and use of paroxetine, a new selective serotonin reuptake inhibitor. Pharmacotherapy 1994; 14: 127–38

    PubMed  CAS  Google Scholar 

  60. Stokes PE. Fluoxetine: a five-year review. Clin Ther 1993; 15: 216–43

    PubMed  CAS  Google Scholar 

  61. Borys DJ, Setzer SC, King LJ. Acute fluoxetine overdose: a report of 234 cases. Am J Emerg Med 1992; 10: 115–20

    PubMed  CAS  Google Scholar 

  62. Wagner W, Plekkenpol B, Gray TE, et al. Review of fluvoxamine safety database. Drugs 1992; 43 Suppl. 2: 48–54

    PubMed  Google Scholar 

  63. Doogan DP, Caillard V. Sertraline; a new antidepresant. J Clin Psychiatr 1988; 49: 46–55

    Google Scholar 

  64. Jonsson B, Bebbington PE. What price depression? The cost of depression and the cost-effectiveness of pharmacological treatment. Br J Psychiatr 1994; 164: 665–73

    CAS  Google Scholar 

  65. Kelvin AS, Hakansson S. Comparative acute toxicity of paroxetine and other antidepressants. Acta Psychiatr Scand 1989; Suppl. 350: 31–3

    Google Scholar 

  66. Budavari S, O’Neil MJ, Smith A, et al, editors. The Merck Index. 11th ed. Rahway, NJ: Merck & Co., Inc., 1989; 4112

    Google Scholar 

  67. Investigator’s brochure — sertraline hydrochloride. Groton, CT: Pfizer Inc., Central Research Division Departmnent of Clinical Research, 1991: 4–5

  68. Dollery CT, editor. Therapeutic drugs. Supplement 2. Edinburgh: Churchill Livingstone, 1994: 48

    Google Scholar 

  69. Data on file — Venlafaxine. Wyeth-Ayerst Study Protocol No 600A-350

  70. Fontaine R, Ontiveros A, Elie R, et al. A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiat 1994; 55: 234–41

    CAS  Google Scholar 

  71. Product Monograph — Serzone (Nefazodone Hydrochloride). Montreal: Bristol-Myers Squibb Canada Inc, 1995

  72. Tucker WE. Preclinical toxicology of bupropion: an overview. J Clin Psychiat 1983; 44: 60–2

    CAS  Google Scholar 

  73. Jenner PN. Paroxetine: an overview of dosage, tolerability and safety. Int Clin Psychopharmacol 1992; 6 Suppl. 4: 69–80

    PubMed  Google Scholar 

  74. Garnier R, Azoyan P, Chataigner D, et al. Acute fluvoxamine poisoning. J Int Med Res 1993; 21: 197–208

    PubMed  CAS  Google Scholar 

  75. Milne RJ, Goa KL. Citalopram: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 1991; 41: 450–77

    PubMed  CAS  Google Scholar 

  76. Kelvin AS, Hakansson S. Comparative acute toxicity of paroxetine and other antidepressants. Acta Psychiatr Scand 1989; 80 Suppl. 3: 31–3

    Google Scholar 

  77. Henry JA. Overdose and safety with fluvoxamine. Int Clin Psychopharmacol 1991; 6: 41–7

    PubMed  Google Scholar 

  78. Murdoch D, McTavish D. Sertraline: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs 1992; 44: 604–24

    PubMed  CAS  Google Scholar 

  79. Fontaine R. Novel serotonergic mechanisms and clinical experience with nefazodone. Clin Neuropharmacol 1993; 16 Suppl. 3: S45–S50

    PubMed  Google Scholar 

  80. Perry PJ, Ellingrod VL. Venlafaxine: a heterocyclic antidepressant. Am J Hosp Pharm 1994; 51: 3033–46

    PubMed  Google Scholar 

  81. Crewe HK, Lennard MS, Tucker GT, et al. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 1992; 34: 262–5

    PubMed  CAS  Google Scholar 

  82. Otton SV, Wu D, Joffe RT, et al. Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clin Pharmcol Ther 1993; 53: 401–9

    CAS  Google Scholar 

  83. Skjelbo E, Brosen K. Inhibitors of imipramine metabolism by human liver microsomes. Br J Clin Pharmacol 1992; 34: 256–61

    PubMed  CAS  Google Scholar 

  84. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. J Pharmacol Exp Ther 1994; 268: 1278–83

    Google Scholar 

  85. Stevens JC, Wrighton SA. Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P 450. J Pharmacol Exp Ther 1993; 266: 964–71

    PubMed  CAS  Google Scholar 

  86. van Harten J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmacokinet 1993; 24: 203–20

    PubMed  Google Scholar 

  87. Brosen K, Hansen M, Nielsen KK, et al. Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur J Clin Pharmacol 1993; 44: 349–55

    PubMed  CAS  Google Scholar 

  88. Drake WM, Gordon GD. Heart block in a patient on propranolol and fluoxetine. Lancet 1994; 343: 425–6

    PubMed  CAS  Google Scholar 

  89. Brøsen K. The pharmacogenetics of selective serotonin reuptake inhibitors. Clin Invest 1993; 71: 1002–9

    Google Scholar 

  90. Preskorn SH, Alderman J, Chung M, et al. Pharmacokinetics of desipramine coadministered with seraline or fluoxetine. J Clin Psychopharmacol 1994; 14: 90–8

    PubMed  CAS  Google Scholar 

  91. von Moltke, LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 1994; 38: 23–31

    CAS  Google Scholar 

  92. Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10,11-epoxide formation. Biochem Pharmacol 1994; 47: 1969–79

    PubMed  CAS  Google Scholar 

  93. Dursun SM, Mathew VM, Reveley MA. Toxic serotonin syndrome after fluoxetine plus carbamazepine. Lancet 1993; 342: 442–3

    PubMed  CAS  Google Scholar 

  94. Brøsen K, Skjelbo E, Rasmussen BB, et al. Fluvoxamine is a potent inhibitor of cytochrome P4501A2. Biochem Pharmacol 1993; 45: 1211–4

    PubMed  Google Scholar 

  95. Diot P, Jonville AP, Gerard F, et al. Possible interaction between theophylline and fluvoxamine. Therapie 1991; 46: 170–1

    PubMed  CAS  Google Scholar 

  96. Sperber AD. Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year old boy. Drug Saf 1991; 6: 460–2

    PubMed  CAS  Google Scholar 

  97. van Den Brekel AM, Harrington L. Toxic effects of theophylline caused by fluvoxamine. Can Med Assoc J 1994; 151: 1289–90

    Google Scholar 

  98. Spina E, Campo GM, Avenoso A, et al. Interaction between fluvoxamine and imipraminel desipramine in four patients. Ther Drug Monit 1992; 14: 194–6

    PubMed  CAS  Google Scholar 

  99. Spina E, Pollicine AM, Avenoso A, et al. Effect of fluvoxamine on the pharmacokinetics of imipramine and desipramine in healthy subjects. Ther Drug Monit 1993; 15: 243–6

    PubMed  CAS  Google Scholar 

  100. Jerling M, Lindstrom L, Bondesson U, et al. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 1994; 16: 368–74

    PubMed  CAS  Google Scholar 

  101. Hiemke C, Weigmann H, Hartter S, et al. Elevated levels of clozapine in serum after addition of fluvoxamine. J Clin Psychopharmacol 1994; 14: 279–81

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  103. Hulten BA, Heath A, Knudsen K, et al. Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics. J Toxicol Clin Toxicol 1992; 30: 171–9

    PubMed  CAS  Google Scholar 

  104. Bramble MG, Lishman AH, Purdon B, et al. An analysis of plasma levels and 24-hour ECG recordings in tricyclic antidepressant poisoning: implications for management. Q J Med 1985; 56(219): 357–66

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  108. Dumovic P, Burrows GD, Vohra J, et al. The effect of tricyclic antidepressant drugs on the heart. Arch Toxicol 1976; 35: 255–62

    PubMed  CAS  Google Scholar 

  109. Hanson RW, Desser KB, Benchimol A. Cardiovascular effects of tricyclic antidepressants. Ariz Med 1982; 39: 368–70

    PubMed  CAS  Google Scholar 

  110. Thorstrand C. Cardiovascular effects of poisoning with tricyclic antidepressants. Acta Med Scand 1974; 195: 505–14

    PubMed  CAS  Google Scholar 

  111. Jammehdiabadi M, Tierney M. Impact of toxicology screens in the diagnosis of a suspected overdose: salicylates, tricyclic antidepressants and benzodiazepines. Vet Hum Toxicol 1991; 33: 40–3

    PubMed  CAS  Google Scholar 

  112. Rudorfer MV, Robins E. Amitriptyline overdose: clinical effects on tricyclic antidepressant levels. J Clin Psychiatr 1982; 43: 457–60

    CAS  Google Scholar 

  113. Bailey DN, Van Dyke C, Langou RA, et al. Tricyclic antidepressants: plasma levels and clinical findings in overdose. Am J Psychiatr 1978; 135: 1325–8

    PubMed  CAS  Google Scholar 

  114. 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 

  115. Pedersen OL, Gram LF, Kristensen CB, et al. Overdosage of antidepressants: clinical and pharmacokinetic aspects. Eur J Clin Pharmacol 1982; 23: 513–21

    PubMed  CAS  Google Scholar 

  116. Braithwaite RA, Crome P, Dawling S. Amitriptyline overdosage: plasma concentrations and clinical features. Proceedings of the British Pharmacology Society, 1979 Jul 17–20; 388–9

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

    PubMed  CAS  Google Scholar 

  118. Caravati EM, Bossarti PJ. Demographic and electrocardio-graphic factors associated with severe tricyclic antidepressant toxicity. Clin Toxicol 1991; 29: 31–43

    CAS  Google Scholar 

  119. 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

    PubMed  CAS  Google Scholar 

  120. Marshall JB, Forker AD. Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J 1982; 103: 401–14

    PubMed  CAS  Google Scholar 

  121. 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 

  122. Boehnert MT, Lovejoy 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

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  124. Groleau G, Jotte R, Barish R. The electrocardiographic manifestations of cyclic antidepressant therapy and overdose: a review. J Emerg Med 1990; 8: 597–605

    PubMed  CAS  Google Scholar 

  125. 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

    PubMed  CAS  Google Scholar 

  126. Jones DW, editor. Toxi-Lab Compendium. Laguna Wills, CA: Analytical Systems, Division of Marion Laboratories, Inc., 1985

    Google Scholar 

  127. Mazhar M, Binder SR. Analysis of benzodiazepines and tricyclic antidepressants in whole blood using a common solid-phase clean-up and a common mobile phase. In: Sunshine I, editor. Recent developments in therapeutic drug monitoring and clinical toxicology. New York: Marcel Dekker, Inc., 1992: 325–35

    Google Scholar 

  128. Wong SHY. Measurement of antidepressants by liquid chromatography: a review of current methodology. Clin Chem 1988; 34: 858–5

    Google Scholar 

  129. Strolin Benedetti M, Rovei V, Dencker ST et al. Pharmacokinetics of toloxatone in man following intravenous and oral administration. Arzneimittelforschung 1982; 32: 276–80

    CAS  Google Scholar 

  130. Gifford LA, Turner P, Pare CMB. Sensitive method for the routine determination of tricyclic antidepressnats in plasma using a specific nitrogen detector. J Chromatogr 1975; 105: 107–13

    PubMed  CAS  Google Scholar 

  131. Scoggins BA, Maguire KP, Norman TR, et al., Measurement of tricyclic antidepressants. Clin Chem 1980; 26: 5–17

    PubMed  CAS  Google Scholar 

  132. Rohrig TP, Ray NG. Tissue distribution of bupropion in a fatal overdose. J Anal Toxicol 1992; 16: 343–5

    PubMed  CAS  Google Scholar 

  133. Friel PN, Logan BK, Fligner CL. Three fatal overdoses involving bupropion. J Anal Toxicol 1993; 17: 436–8

    PubMed  CAS  Google Scholar 

  134. Anonymous. Tricyclic antidepressants. In: Tdx Assays Manual R-101. North Chicago: Abbott Laboratories USA, 1985: 1–6

  135. Hackett LP, Dusci LJ, Ilett KF. Evaluation of fluorescence polarisation immunoassay for use in monitoring plasma dothiepin levels in overdose cases. In: Sunshine I, editor. Recent developments in therapeutic drug monitoring and clinical toxicology. New York: Marcel Dekker, Inc., 1992: 297–311

    Google Scholar 

  136. Ilett KF, Hackett LP, Dusci LJ, et al. Disposition of dothiepin after overdose: effects of repeated-dose activated charcoal. Ther Drug Monit 1991; 13: 485–9

    PubMed  CAS  Google Scholar 

  137. Orsulak P. Therapeutic monitoring of antidepressant drugs: current methodology and applications. J Clin Psychiatr 1986; 47 Suppl.: 39–50

    CAS  Google Scholar 

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Authors and Affiliations

  1. Intensive Care Unit, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

    Bradley M. Power

  2. Clinical Pharmacology & Toxicology Laboratory, The Western Australian Centre for Pathology and Medical Research, Nedlands, Western Australia, Australia

    L. Peter Hackett, Leon J. Dusci &  Kenneth F. Ilett

  3. Department of Pharmacology, University of Western Australia, Nedlands, Western Australia, 6009, Australia

    Kenneth F. Ilett

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  1. Bradley M. Power
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Power, B.M., Hackett, L.P., Dusci, L.J. et al. Antidepressant Toxicity and the Need for Identification and Concentration Monitoring in Overdose. Clin-Pharmacokinet 29, 154–171 (1995). https://doi.org/10.2165/00003088-199529030-00003

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