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Antipsychotics

Critical Care Toxicology

Abstract

The discovery of chlorpromazine and other traditional antipsychotic agents in the early 1950s revolutionized the management of schizophrenia and led to a dramatic reduction in the number of hospitalizations necessary for patients with psychosis. Shortly after their introduction, however, it was noted that these agents often produced disabling neurological side effects (e.g., sedation, extrapyramidal side effects [EPS], tardive dyskinesia [TD]) and were ineffective against the negative symptoms (e.g., anhedonia, apathy, inactivity, poverty of thought, social withdrawal) and neurocognitive deficits of schizophrenia. Initially, it was thought that EPS were linked inextricably to antipsychotic drug action. The introduction of clozapine in 1990 and other so-called atypical agents shortly thereafter has further revolutionized the management of schizophrenia. Compared with traditional antipsychotics, atypical agents produce minimal EPS at clinically effective antipsychotic doses and seem to be more effective for the negative symptoms and neurocognitive deficits of schizophrenia. This chapter describes in detail the pharmacology and toxicology of traditional and atypical antipsychotic agents.

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References

  1. Tandon R, Milner K, Jibson MD. Antipsychotics from theory to practice: integrating clinical and basic data. J Clin Psychiatry. 1999;60 Suppl 8:21–8.

    PubMed  Google Scholar 

  2. Buckley N, McManus P. Fatal toxicity of drugs used in the treatment of psychotic illnesses. Br J Psychiatry. 1998;172:461–4.

    Article  CAS  PubMed  Google Scholar 

  3. Buckley NA, Whyte IM, Dawson AH. Thioridazine has greater cardiotoxicity in overdose than other neuroleptics. J Toxicol Clin Toxicol. 1995;33:199–204.

    Article  CAS  PubMed  Google Scholar 

  4. Flanagan RJ. Fatal toxicity of drugs used in psychiatry. Hum Psychopharmacol Clin Exp. 2008;23:43–51.

    Article  Google Scholar 

  5. Mowry JB, Spyker DA, Cantilena LR, et al. 2012 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 30th annual report. J Toxicol Clin Toxicol. 2013;51:949–1229.

    Article  CAS  Google Scholar 

  6. Meyer JM. Pharmacotherapy of Psychosis and Mania. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill; 2011. p. 417–55.

    Google Scholar 

  7. Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry. 1999;60 Suppl 10:5–14.

    CAS  PubMed  Google Scholar 

  8. Jibson MD, Tandon R. New atypical antipsychotic medications. J Psychiatr Res. 1998;32:215–28.

    Article  CAS  PubMed  Google Scholar 

  9. Blin O. A comparative review of new antipsychotics. Can J Psychiatry. 1999;44:235–44.

    CAS  PubMed  Google Scholar 

  10. Casey D. The relationship of pharmacology to side effects. J Clin Psychiatry. 1997;58 Suppl 10:55–62.

    CAS  PubMed  Google Scholar 

  11. Goren JL, Levin GM. Quetiapine, an atypical antipsychotic. Pharmacotherapy. 1998;18:1183–94.

    CAS  PubMed  Google Scholar 

  12. Markowitz JS, Brown CS, Moore TR. Atypical antipsychotics: part I. Pharmacology, pharmacokinetics, and efficacy. Ann Pharmacother. 1999;33:73–85.

    Article  CAS  PubMed  Google Scholar 

  13. Pickar D. Prospects for pharmacotherapy of schizophrenia. Lancet. 1995;345:557–62.

    Article  CAS  PubMed  Google Scholar 

  14. Seeger TF, Seymour PA, Schmidt AW, et al. Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther. 1995;275:101–13.

    CAS  PubMed  Google Scholar 

  15. Bymaster FP, Perry KW, Nelson DL, et al. Olanzapine: a basic science update. Br J Psychiatry. 1999;174 Suppl 37:36–40.

    Google Scholar 

  16. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther. 1989;251:238–46.

    CAS  PubMed  Google Scholar 

  17. Borison RL. Recent advances in the pharmacotherapy of schizophrenia. Harv Rev Psychiatry. 1997;4:255–71.

    Article  CAS  PubMed  Google Scholar 

  18. Kinon BJ, Lieberman JA. Mechanisms of action of atypical antipsychotic drugs: a critical analysis. Psychopharmacology (Berl). 1996;124:2–34.

    Article  CAS  Google Scholar 

  19. Brody TM, Larner J, Minneman KP, editors. Human pharmacology: molecular to clinical. 3rd ed. St. Louis: Mosby; 1998. p. 342.

    Google Scholar 

  20. Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic dopamine receptors. Nature. 1976;261:717–9.

    Article  CAS  PubMed  Google Scholar 

  21. Farde L, Nordstrom AL, Wiesel GA, et al. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992;49:538–44.

    Article  CAS  PubMed  Google Scholar 

  22. Risch SC. Pathophysiology of schizophrenia and the role of newer antipsychotics. Pharmacotherapy. 1996;16(Suppl):11–4.

    CAS  PubMed  Google Scholar 

  23. Burris KD, Molski TF, Xu C, et al. Aripiprazole, a novel antipsychotic is a high-affinity partial agonist at human D2 receptors. J Pharmacol Exp Ther. 2002;302:381–9.

    Article  CAS  PubMed  Google Scholar 

  24. Jordan S, Koprivica V, Chen R, et al. The antipsychotic aripiprazole as a potent partial agonist at the human 5-HT1A receptor. Eur J Pharmacol. 2002;441:137–40.

    Article  CAS  PubMed  Google Scholar 

  25. Black JL, Richelson E. Antipsychotic drugs: prediction of side effect profiles based on neuroreceptor data derived from human brain tissue. Mayo Clin Proc. 1987;62:369–72.

    Article  CAS  PubMed  Google Scholar 

  26. Kapur S, Remington G. Serotonin-dopamine interaction and its relevance to schizophrenia. Am J Psychiatry. 1996;153:466–76.

    Article  CAS  PubMed  Google Scholar 

  27. Lieberman JA, Mailman RB, Duncan G, et al. Serotonergic basis of antipsychotic drug effects in schizophrenia. Biol Psychiatry. 1998;44:1099–117.

    Article  CAS  PubMed  Google Scholar 

  28. Huttunen M. The evolution of the serotonin-dopamine antagonist concept. J Clin Psychopharmacol. 1995;15 Suppl 1:4S–10.

    Article  CAS  PubMed  Google Scholar 

  29. Carlsson A, Walters N, Carlsson ML. Neurotransmitter interactions in schizophrenia – therapeutic implications. Biol Psychiatry. 1999;46:1388–95.

    Article  CAS  PubMed  Google Scholar 

  30. Snyder S, Greenberg D, Yamamura JI. Antischizophrenic drugs and brain cholinergic receptors: affinity for muscarinic sites predicts extrapyramidal effects. Arch Gen Psychiatry. 1974;31:58–61.

    Article  CAS  PubMed  Google Scholar 

  31. Gerlach J, Peacock L. New antipsychotics: the present status. Int Clin Psychopharmacol. 1995;10 Suppl 3:39–48.

    PubMed  Google Scholar 

  32. Ogata N, Narahashi T. Block of sodium channels by psychotropic drugs in single guinea-pig cardiac myocytes. Br J Pharmacol. 1989;97:905–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kongsamut S, Kang J, Chen X, Roehr J, et al. A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs. Eur J Pharmacol. 2002;450(1):37–41.

    Article  CAS  PubMed  Google Scholar 

  34. Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns? Curr Pharm Des. 2004;10(20):2463–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gould RJ, Murphy KMM, Reynolds IJ, et al. Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists. Proc Natl Acad Sci U S A. 1983;86:5122–5.

    Article  Google Scholar 

  36. Gould RJ, Murphy KMM, Reynolds IJ, et al. Calcium channel blockade: possible explanation for thioridazine’s peripheral side effects. Am J Psychiatry. 1984;141:352–7.

    Article  CAS  PubMed  Google Scholar 

  37. Arnoult C, Cardullo RA, Lemos JR, Florman HM. Activation of mouse sperm T-type Ca2+ channels by adhesion to the egg zona pellucida. Proc Natl Acad Sci U S A. 1996;93:13004–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cold JA, Wells BG, Froemming JH. Seizure activity associated with antipsychotic therapy. Drug Intell Clin Pharm. 1990;24:601–6.

    CAS  Google Scholar 

  39. Logothetis J. Spontaneous epileptic seizures and electroencephalographic changes in the course of phenothiazine therapy. Neurology. 1967;17:869–77.

    Article  CAS  PubMed  Google Scholar 

  40. Devinsky O, Honigfeld G, Patin J. Clozapine-related seizures. Neurology. 1991;41(3):369–71.

    Article  CAS  PubMed  Google Scholar 

  41. Alldredge BK. Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations. Neurology. 1999;53 Suppl 2:S68–75.

    CAS  PubMed  Google Scholar 

  42. Peterson C. Seizures induced by acute loxapine overdose. Am J Psychiatry. 1981;138:1089–91.

    Article  CAS  PubMed  Google Scholar 

  43. Rupniak NMJ, Jenner P, Marsden CD. Acute dystonia induced by neuroleptic drugs. Psychopharmacology (Berl). 1986;88:403–19.

    Article  CAS  Google Scholar 

  44. Baldessarini RJ, Tarsy D. Dopamine and the pathophysiology of dyskinesia induced by antipsychotic drugs. Annu Rev Neurosci. 1980;3:23–41.

    Article  CAS  PubMed  Google Scholar 

  45. Jeanjean AP, Laterre C, Maloteaux J-M. Neuroleptic binding to sigma receptors: possible involvement in neuroleptic-induced dystonia. Biol Pyschiatry. 1997;41:1010–9.

    Article  CAS  Google Scholar 

  46. Marsden CD, Jenner P. The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Psychol Med. 1980;10:55–72.

    Article  CAS  PubMed  Google Scholar 

  47. Kolbe H, Clow A, Jenner P, et al. Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release or to supersensitive postsynaptic receptors. Neurology. 1981;31:434–9.

    Article  CAS  PubMed  Google Scholar 

  48. Cadet JL, Lohr JB. Possible involvement of free radicals in neuroleptic-induced movement disorders. Ann N Y Acad Sci. 1989;570:176–85.

    Article  CAS  PubMed  Google Scholar 

  49. Javaid JI. Clinical pharmacokinetics of antipsychotics. J Pharmacol. 1994;34:286–95.

    CAS  Google Scholar 

  50. Ereshefsky L. Pharmacokinetics and drug interactions: update for new antipsychotics. J Clin Psychiatry. 1996;57 Suppl 11:12–25.

    CAS  PubMed  Google Scholar 

  51. Spyker DA, Munzar P, Cassella JV. Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers. J Clin Pharmacol. 2010;50(2):169–79.

    Article  CAS  PubMed  Google Scholar 

  52. Fang J, Gorrod JW. Metabolism, pharmacogenetics, and metabolic drug-drug interactions of antipsychotic drugs. Cell Mol Neurobiol. 1999;19:491–510.

    Article  CAS  PubMed  Google Scholar 

  53. Dahl ML, Bertilsson L. Genetically variable metabolism of antidepressants and neuroleptics. Pharmacogenetics. 1993;3:61–70.

    Article  CAS  PubMed  Google Scholar 

  54. Goff DC, Baldessarini RJ. Drug interactions with antipsychotic agents. J Clin Psychopharmacol. 1993;13:57–67.

    Article  CAS  PubMed  Google Scholar 

  55. Edge SC, Markowitz JS, DeVane CL. Clozapine drug interactions: a review of the literature. Hum Psychopharmacol. 1997;12:5–20.

    Article  CAS  Google Scholar 

  56. Klimke A, Klieser E. Sudden death after intravenous application of lorazepam in a patient treated with clozapine (Letter). Am J Psychiatry. 1994;151:780.

    CAS  PubMed  Google Scholar 

  57. Tanaka E, Hisawa S. Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharm Ther. 1999;24:7–16.

    Article  CAS  PubMed  Google Scholar 

  58. Taylor D. Pharmacokinetic interactions involving clozapine. Br J Psychiatry. 1997;171:109–12.

    Article  CAS  PubMed  Google Scholar 

  59. Cohen LG, Chesley S, Eugenio L, et al. Erythromycin-induced clozapine toxic reaction. Arch Intern Med. 1996;156:675–7.

    Article  CAS  PubMed  Google Scholar 

  60. Funderburg LG, Vertrees JE, True JE, Miller AL. Seizure following addition of erythromycin to clozapine treatment. Am J Psychiatry. 1994;151:1840–1.

    CAS  PubMed  Google Scholar 

  61. Stevens I, Gaertner HJ. Plasma level measurement in a patient with clozapine intoxication. J Clin Psychopharmacol. 1996;16:86–7.

    Article  CAS  PubMed  Google Scholar 

  62. Desta Z, Kerbusch T, Glockhart DA. Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6). Clin Pharmacol Ther. 1999;65:10–20.

    Article  CAS  PubMed  Google Scholar 

  63. Lee HS, Tan CH, Au LSY. Serum and urine risperidone concentrations in acute overdose. J Clin Psychopharmacol. 1997;17:325–6.

    Article  CAS  PubMed  Google Scholar 

  64. Mahutte CK, Nakassuto SK, Light RW. Haloperidol and sudden death due to pulmonary edema. Arch Intern Med. 1982;142:1951–2.

    Article  CAS  PubMed  Google Scholar 

  65. Li C, Gefter WB. Acute pulmonary edema induced by overdosage of phenothiazines. Chest. 1992;101:102–4.

    Article  CAS  PubMed  Google Scholar 

  66. Acri AA, Henretig FM. Effects of risperidone in overdose. Am J Emerg Med. 1998;16:498–501.

    Article  CAS  PubMed  Google Scholar 

  67. LeBlaye I, Donatini B, Hall M, Krupp P. Acute overdosage with clozapine: a review of the available clinical experience. Pharm Med. 1992;6:169–78.

    Google Scholar 

  68. O’Malley GF, Seifert S, Heard K, et al. Olanzapine overdose mimicking opioid intoxication. Ann Emerg Med. 1999;34:279–81.

    Article  PubMed  Google Scholar 

  69. Harmon TJ, Benitez JG, Krenzelok EP, Cortes-Belen E. Loss of consciousness from acute quetiapine overdosage. J Toxicol Clin Toxicol. 1998;36:599–602.

    Article  CAS  PubMed  Google Scholar 

  70. Barry D, Meyskens FL, Becker CE. Phenothiazine poisoning: a review of 48 cases. Calif Med. 1973;118:1–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Luedecke D, Schottle D, Karow A, et al. Post-injection delirium/sedation syndrome in patients treated with olanzapine pamoate: mechanism, incidence, and management. CNS Drugs. 2015;29(1):41–6.

    Article  CAS  PubMed  Google Scholar 

  72. Novakovic V, Adel T, Peselow E, Lindenmayer JP. Long-acting injectable antipsychotics and the development of postinjection delirium/sedation syndrome (PDSS). Clin Neuropharmacol. 2013;36(2):59–62.

    Article  CAS  PubMed  Google Scholar 

  73. Detke HC, McDonnell DP, Brunner E, et al. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry. 2010;10:43.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Mitchell AA, Lovejoy FH, Goldman P. Drug ingestions associated with miosis in comatose children. J Pediatr. 1976;89:303–5.

    Article  CAS  PubMed  Google Scholar 

  75. Mady S, Wax P, Wang D, et al. Pediatric clozapine intoxication. Am J Emerg Med. 1996;14:462–3.

    Article  CAS  PubMed  Google Scholar 

  76. Bonin MM, Burkhart KK. Olanzapine overdose in a 1-year old male. Pediatr Emerg Care. 1999;15:266–7.

    Article  CAS  PubMed  Google Scholar 

  77. Cheslik TA, Erramouspe J. Extrapyramidal symptoms following accidental ingestion of risperidone in a child. Ann Pharmacother. 1996;30:360–3.

    CAS  PubMed  Google Scholar 

  78. Tam CW, Olin BR, Ruiz AE. Loxapine-associated rhabdomyolysis and acute renal failure. Arch Intern Med. 1980;140:975–6.

    Article  CAS  PubMed  Google Scholar 

  79. Yip L, Dart RC, Graham K. Olanzapine toxicity in a toddler (Letter). Pediatrics. 1998;102:1494.

    Article  CAS  PubMed  Google Scholar 

  80. Bond GR, Thompson JD. Olanzapine pediatric overdose (Letter). Ann Emerg Med. 1999;34:292–3.

    Article  CAS  PubMed  Google Scholar 

  81. McGuigan MA. Phenothiazines. Clin Toxicol Rev. 1981;3:4–14.

    Google Scholar 

  82. Meeker JE, Herrmann PW, Som SW, Reynolds PC. Clozapine tissue concentrations following an apparent suicidal overdose of Clozaril. J Anal Toxicol. 1992;16:54–6.

    Article  CAS  PubMed  Google Scholar 

  83. Elian AA. Fatal overdose of olanzepine. Forensic Sci Int. 1998;91:231–5.

    Article  CAS  PubMed  Google Scholar 

  84. Elkayam U, Frishman W. Cardiovascular effects of phenothiazines. Am Heart J. 1980;100:397–401.

    Article  CAS  PubMed  Google Scholar 

  85. Fowler ND, McCall D, Chou T, et al. Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs. Am J Cardiol. 1981;37:223–30.

    Article  Google Scholar 

  86. Fletcher GF, Kazamias TM, Wenger NK. Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias. Am Heart J. 1961;78:135–8.

    Article  Google Scholar 

  87. Fulop G, Phillips RA, Shapiro AK, et al. ECG changes during haloperidol and pimozide treatment of Tourette’s disorder. Am J Psychiatry. 1987;144:673–5.

    Article  CAS  PubMed  Google Scholar 

  88. Marris-Simon P, Zell-Kanter M, Kendzlerski D, et al. Cardiotoxic manifestations of mesoridazine overdose. Ann Emerg Med. 1988;17:1074–8.

    Article  Google Scholar 

  89. Thornton CC, Wendkos MH. EKG T-wave distortions among thioridazine-treated psychiatric inpatients. Dis Nerv Syst. 1971;32:320–3.

    CAS  PubMed  Google Scholar 

  90. Neimann JT, Stapczynski JS, Rothstein RJ, et al. Cardiac conduction and rhythm disturbances following suicidal ingestion of mesoridazine. Ann Emerg Med. 1981;10:585–8.

    Article  Google Scholar 

  91. Lee AM, Knoll JL, Suppes R. The atypical antipsychotic sertindole: a case series. J Clin Psychiatry. 1997;58:410–6.

    Article  CAS  PubMed  Google Scholar 

  92. Brown K, Levy H, Brenner C, et al. Overdose of risperidone. Ann Emerg Med. 1993;22:1908–10.

    Article  CAS  PubMed  Google Scholar 

  93. Lynch S, Fill S, Hoffman RS. Intentional quetiapine (Seroquel) overdose (Abstract). J Toxicol Clin Toxicol. 1999;37:631.

    Google Scholar 

  94. Hustey FM. Acute quetiapine poisoning. J Emerg Med. 1999;17:995–7.

    Article  CAS  PubMed  Google Scholar 

  95. Kopala LC, Day C, Dillman B, Gardner D. A case of risperidone overdose in early schizophrenia: a review of potential complications. J Psychiatry Neurosci. 1998;23:305–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Palatnick W, Meatherall R, Tenenbein M. Ventricular tachycardia associated with remoxipride overdose (Abstract). J Toxicol Clin Toxicol. 1995;33:492.

    Google Scholar 

  97. Flugelman MY, Tal A, Pollack S, et al. Psychotropic drugs and long QT syndromes: case reports. J Clin Psychiatry. 1985;46:290–1.

    CAS  PubMed  Google Scholar 

  98. Aunsholt NA. Prolonged QT interval and hypokalemia caused by haloperidol. Acta Psychiatr Scand. 1989;79:411–2.

    Article  CAS  PubMed  Google Scholar 

  99. Lawrence KR, Nasraway SA. Conduction disturbances associated with administration of butyrophenone antipsychotics in the critically ill: a review of the literature. Pharmacotherapy. 1997;17:531–7.

    CAS  PubMed  Google Scholar 

  100. Frye MA, Coudreaut MF, Hakeman SM, et al. Continuous droperidol infusion for management of agitated delirium in an intensive care unit. Psychosomatics. 1995;36:301–5.

    Article  CAS  PubMed  Google Scholar 

  101. Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med. 1994;22:433–40.

    Article  CAS  PubMed  Google Scholar 

  102. Krahenbuhl SI, Sauter B, Kupferschmidt H, et al. Reversible QT prolongation with torsades de pointes in a patient with pimozide intoxication. Am J Med Sci. 1995;309:315–6.

    Article  CAS  PubMed  Google Scholar 

  103. Tamminga CA. The promise of new drugs for schizophrenia treatment. Can J Psychiatry. 1997;42:265–73.

    CAS  PubMed  Google Scholar 

  104. Glassman AH, Bigger JT. Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001;158(11):1774–82.

    Article  CAS  PubMed  Google Scholar 

  105. Ravin DS, Levenson JW. Fatal cardiac event following initiation of risperidone therapy. Ann Pharmacother. 1997;31:867–70.

    CAS  PubMed  Google Scholar 

  106. Mehtonen OP, Aranko K, Malkonen L, et al. A survey of sudden death associated with the use of antipsychotic or antidepressant drugs: 49 cases in Finland. Acta Psychiatr Scand. 1991;84:58–64.

    Article  CAS  PubMed  Google Scholar 

  107. Hollister LE, Kosek JV. Sudden death during treatment with phenothiazine derivatives. JAMA. 1965;192:1035–8.

    Article  CAS  PubMed  Google Scholar 

  108. Selim K, Kaplowitz N. Hepatotoxicity of psychotropic drugs. Hepatology. 1999;29:1347–51.

    Article  CAS  PubMed  Google Scholar 

  109. Hummer M, Kurz M, Kurzthalaer I, et al. Hepatotoxicity of clozapine. J Clin Psychopharmacol. 1997;17:314–7.

    Article  CAS  PubMed  Google Scholar 

  110. Ishak K, Irey N. Hepatic injury associated with the phenothiazines. Arch Pathol. 1972;93:283–304.

    CAS  PubMed  Google Scholar 

  111. Derby L, Gutthann SP, Jick H, Dean A. Liver disorders in patients receiving chlorpromazine or isoniazid. Pharmacotherapy. 1993;13:354–8.

    Google Scholar 

  112. Litvak R, Kaelbling R. Agranulocytosis, leukopenia and psychotropic drugs. Arch Gen Psychiatry. 1971;24:265–7.

    Article  CAS  PubMed  Google Scholar 

  113. Trayle WH. Phenothiazine-induced agranulocytosis (Letter). JAMA. 1986;256:1957.

    Article  Google Scholar 

  114. Alvir J, Lieberman J, Safferman A, et al. Clozapine-induced agranulocytosis: incidence and risk factors in the United States. N Engl J Med. 1993;329:162–7.

    Article  CAS  PubMed  Google Scholar 

  115. Safferman A, Lieberman JA, Kane JM, et al. Update on the clinical efficacy and side effects of clozapine. Schizophr Bull. 1991;17:247–61.

    Article  CAS  PubMed  Google Scholar 

  116. Lorenz M, Evering WE, Provencher A, et al. Atypical antipsychotic-induced neutropenia in dogs. Toxicol Appl Pharmacol. 1999;155:227–36.

    Article  CAS  PubMed  Google Scholar 

  117. Geibig CB, Marks LW. Treatment of clozapine- and molindone-induced agranulocytosis with granulocyte colony-stimulating factor. Ann Pharmacother. 1993;27:1190–4.

    CAS  PubMed  Google Scholar 

  118. Muscettola G, Barbato G, Pampallona D, et al. Extrapyramidal syndromes in neuroleptic-treated patients: prevalence, risk factors, and association with tardive dyskinesia. J Clin Psychopharmacol. 1999;19:203–8.

    Article  CAS  PubMed  Google Scholar 

  119. Cortese L, Pourcher-Bouchard E, Williams R. Assessment and management of antipsychotic-induced adverse events. Can J Psychiatry. 1998;43 Suppl 1:15S–20.

    PubMed  Google Scholar 

  120. Swett C. Drug-induced dystonia. Am J Psychiatry. 1982;132:532–4.

    Google Scholar 

  121. Ayd FJ. A survey of drug-induced extrapyramidal reactions. JAMA. 1961;175:1054–60.

    Article  CAS  PubMed  Google Scholar 

  122. Koek RJ, Edmond HP. Acute laryngeal dystonic reactions to neuroleptics. Psychosomatics. 1989;30:359–64.

    Article  CAS  PubMed  Google Scholar 

  123. Drotts DL, Vinson DR. Prochlorperazine induces akathisia in emergency patients. Ann Emerg Med. 1999;34:469–75.

    Article  CAS  PubMed  Google Scholar 

  124. Yassa R, Ananth J, Cordozo S, et al. Tardive dyskinesia in an outpatient population: prevalence and predisposing factors. Can J Psychiatry. 1983;28:391–4.

    CAS  PubMed  Google Scholar 

  125. Brett AS, Rothschild N, Gray R, Perry M. Predicting the clinical course in intentional drug overdose: implications for use of the intensive care unit. Arch Intern Med. 1987;147:133–7.

    Article  CAS  PubMed  Google Scholar 

  126. Tranum BL, Murphy ML. Successful treatment of ventricular tachycardia associated with thioridazine (Mellaril). South Med J. 1969;62:357–8.

    CAS  PubMed  Google Scholar 

  127. Lumpkin J, Watanabe AS, Rumack BH, et al. Phenothiazine-induced ventricular tachycardia following acute overdose. J Am Coll Emerg Physicians. 1979;8:476–8.

    Article  CAS  Google Scholar 

  128. Pietro DA. Thioridazine-associated ventricular tachycardia and isoproterenol (Letter). Ann Intern Med. 1981;94:411.

    Article  CAS  PubMed  Google Scholar 

  129. Kemper A, Dunlop R, Pietro D. Thioridazine-induced torsades de pointes successful therapy with isoproterenol. JAMA. 1983;249:2931–4.

    Article  CAS  PubMed  Google Scholar 

  130. Burns MJ, Linden CH, Graudins A, et al. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med. 2000;35:374–81.

    Article  CAS  PubMed  Google Scholar 

  131. Schuster P, Gabriel E, Luefferie B, et al. Reversal by physostigmine of clozapine-induced delirium. Clin Toxicol. 1977;10:437–41.

    Article  CAS  PubMed  Google Scholar 

  132. Koppel C, Schirop T, Ibe K, et al. Hemoperfusion in chlorprothixene overdose. Intensive Care Med. 1987;13:358–60.

    Article  CAS  PubMed  Google Scholar 

  133. Donlon PT, Tupin JP. Successful suicides with thioridazine and mesoridazine. Arch Gen Psychiatry. 1977;34:955–7.

    Article  CAS  PubMed  Google Scholar 

  134. Hals PA, Jacobsen D. Resin hemoperfusion in levomepromazine poisoning: evaluation of effect on plasma drug and metabolite levels. Hum Toxicol. 1984;3:497–503.

    Article  CAS  PubMed  Google Scholar 

  135. Corre K, Neimann J, Bessen H. Extended therapy for acute dystonic reactions. Ann Emerg Med. 1984;13:194–7.

    Article  CAS  PubMed  Google Scholar 

  136. Vinson DR, Drotts DL. Diphenhydramine prevents akathisia induced by intravenous prochlorperazine: a randomized controlled trial (Abstract). Acad Emerg Med. 1999;6:533.

    Google Scholar 

  137. Adler L, Angrist B, Peselow E, et al. A controlled assessment of propranolol in the treatment of neuroleptic-induced akathisia. Br J Psychiatry. 1983;149:42–5.

    Article  Google Scholar 

  138. Zubenko GS, Cohen BM, Lipinski JF, et al. Use of clonidine in treating neuroleptic-induced akathisia (Letter). Psychiatry Res. 1985;13:253.

    Article  Google Scholar 

  139. Narang P, El-Refai M, Parlapalli R, et al. Antipsychotic drugs: sudden cardiac death among elderly patients. Psychiatry (Edgmont). 2010;7(10):25–9.

    Google Scholar 

  140. United States Food and Drug Administration. Information for healthcare professionals: FDA Alert, conventional antipsychotics. 2008. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm. Last accessed 5 May 2015.

  141. Sharma ND, Rosman HS, Padhi D, Tisdale JE. Torsades de pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol. 1998;81:238–40.

    Article  CAS  PubMed  Google Scholar 

  142. Hegarty AM, Lipton RB, Merriam AE, et al. Cocaine as a risk factor for acute dystonic reactions. Neurology. 1991;41:1670–2.

    Article  CAS  PubMed  Google Scholar 

  143. Lee AS. Treatment of drug-induced dystonic reactions. J Am Coll Emerg Physicians. 1979;8:453–7.

    Article  CAS  Google Scholar 

  144. Freed E. Alcohol-triggered neuroleptic-induced tremor, rigidity and dystonia. Med J Aust. 1981;2:44–5.

    CAS  PubMed  Google Scholar 

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Correspondence to Bradley L. Demeter .

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Demeter, B.L., Burns, M.J. (2015). Antipsychotics. 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_71-1

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  • DOI: https://doi.org/10.1007/978-3-319-20790-2_71-1

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  1. Latest

    Antipsychotics
    Published:
    18 October 2016

    DOI: https://doi.org/10.1007/978-3-319-20790-2_71-2

  2. Original

    Antipsychotics
    Published:
    10 September 2015

    DOI: https://doi.org/10.1007/978-3-319-20790-2_71-1