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Neuroleptic Malignant Syndrome

Recognition, Prevention and Management

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  • Drug Safety Concept
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Abstract

Neuroleptic malignant syndrome (NMS) is a rare but potentially lethal form of drug-induced hyperthermia characterised by mental status changes, muscle rigidity, hyperthermia and autonomic dysfunction. Increased awareness and early recognition will lead to prompt management. The diagnosis of NMS presents a challenge because several medical conditions generate similar symptoms. The presentation and course of NMS can be quite variable ranging from a stormy and potentially fatal course to a relatively benign and self-limiting course. The most important aspect of treatment is prevention. This includes reducing risk factors (e.g. dehydration, agitation and exhaustion), early recognition of suspected cases and prompt discontinuation of the offending agent. All patients with psychosis should be monitored daily for dehydration and elevated temperature, have vital signs checked and agitation should be watched for. Antipsychotics should be used conservatively with gradual titration of doses. The management of NMS should be based on a hierarchy of symptom severity.

Following an episode of NMS, the patient should be reassessed for further treatment with antipsychotics and rechallenge should not be attempted at least 2 weeks following resolution of symptoms of NMS. The patient and family should be educated about the episode and consent for further medication use obtained after a clear explanation of the risk-benefit analysis.

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References

  1. Delay J, Pichot P, Lemperiere T, et al. Un neuroleptique majeur non-phenothiazine et non reserpinique, l’haloperidol, dans 1e traitement des psychoses. Ann Med Psychol 1960; 118: 145–52

    Google Scholar 

  2. Caroff SN. The neuroleptic malignant syndrome. J Clin Psychiatry 1980; 41: 79–83

    PubMed  CAS  Google Scholar 

  3. Delay J, Pichot P, Lemperiere T, et al. L’emploi des butyrophenones en psychiatrie: etude statistique et psychometrique. In: Symposium Internazionale sull’Haloperidol e Triperidol. Milan, Instituto Luso Farmaco d’Italia, 1962; 305–319

    Google Scholar 

  4. Keck PE, Pope HG, McElroy SL. Declining frequency of neuroleptic malignant syndrome in a hospital population. Am J Psychiatry 1991; 148: 880–2

    PubMed  Google Scholar 

  5. Gelenberg AJ, Bellinghausen B, Wojcik JD, et al. Aprospective survey of neuroleptic malignant syndrome in a short-term psychiatric hospital. Am J Psychiatry 1988; 145: 517–8

    PubMed  CAS  Google Scholar 

  6. Keck PE, Pope HG, McElroy SL. Frequency and presentation of neuroleptic malignant syndrome: a prospective study. Am J Psychiatry 1987; 144: 1344–6

    PubMed  Google Scholar 

  7. DSM IV. Diagnostic and Statistical manual of metal disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994: 741–2

    Google Scholar 

  8. Konikoff F, Kuritzky A, Jerushalmi Y, et al. Neuroleptic malignant syndrome induced by a single injection of haloperidol. BMJ 1984; 289: 1228–9

    Article  PubMed  CAS  Google Scholar 

  9. Susman VL, Addonizio G. Reinduction of neuroleptic malignant syndrome by lithium. J Clin Psychopharmacol 1987; 7: 339–41

    Article  PubMed  CAS  Google Scholar 

  10. Goulon M, Rohan-Chabot P, De Elkhaart D, et al. Beneficial effects of dantrolene in the treatment of neuroleptic malignant syndrome: a report of two cases. Neurology 1983; 33: 516–8

    PubMed  CAS  Google Scholar 

  11. Weinberg SE, Twerski RS. Neuroleptic malignant syndrome. Anesth Analg 1983; 62: 848–50

    Article  PubMed  CAS  Google Scholar 

  12. Henderson A, Longdon P. Fulminant metoclopramide-induced neuroleptic malignant syndrome rapidly responsive to intravenous dantrolene. Aust NZ J Med 1991; 21: 742–3

    Article  CAS  Google Scholar 

  13. Lenler-Peterson P, Hansen BD, Hasselstrom L. A rapidly progressing lethal case of neuroleptic malignant syndrome. Intensive Care Med 1990; 16: 267–8

    Article  Google Scholar 

  14. Lavie CJ, Ventura HO, Walker G. Neuroleptic malignant syndrome: three episodes with different drugs. South Med J 1986; 79: 1571–3

    Article  PubMed  CAS  Google Scholar 

  15. Eiser AR, Neff MS, Slifkin RF. Acute myoglobinuric renal failure. Arch Intern Med 1982; 142: 601–3

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. Henderson VW, Wooten GF. Neuroleptic malignant syndrome; a pathogenetic role for dopamine receptor blockade? Neurology 1981; 31: 132–7

    Article  PubMed  CAS  Google Scholar 

  18. Behman S. Mutism induced by phenothiazines. Br J Psychiatry 1972; 121: 599–604

    Article  Google Scholar 

  19. Ansseau M, Diricq ST, Grisar TH, et al. Biochemical and neuroendocrine approaches to a malignant syndrome of neuroleptics. Acta Psychiatr Belg 1980; 80: 600–6

    PubMed  CAS  Google Scholar 

  20. Tu JB. Psychopharmacogenetic basis of medication-induced movement disorders. Int Clin Psychopharmacol 1997 Jan; 12(1): 1–12

    Article  PubMed  CAS  Google Scholar 

  21. Deuschal G, Oepen G, Hermle L, et al. Neuroleptic malignant syndrome: observations on altered consciousness. Pharmacopsychiatry 1987; 20: 168–79

    Article  Google Scholar 

  22. Otani K, Horiuchi M, Kondo T, et al. Is the predisposition to neuroleptic malignant syndrome genetically transmitted? Br J Psychiatry 1991; 158: 850–3

    Article  PubMed  CAS  Google Scholar 

  23. Caroff SN, Mann SC. Neuroleptic malignant syndrome (review). Med Clin North Am 1993; 77: 185–202

    PubMed  CAS  Google Scholar 

  24. Caroff SN, Mann SC. Neuroleptic malignant syndrome. Psychopharmacol Bull 1988; 24: 25–9

    PubMed  CAS  Google Scholar 

  25. Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry 1987; 22: 1004–20

    Article  PubMed  CAS  Google Scholar 

  26. Velamoor VR, Norman R, Caroff SN, et al. Progression of symptoms in neuroleptic malignant syndrome. J Nerv Ment Dis 1994; 182: 168–73

    Article  PubMed  CAS  Google Scholar 

  27. Velamoor VR, Fernando MLD, Williamson P. Incipient neuroleptic malignant syndrome? Br J Psychiatry 1990; 156: 581–4

    Article  PubMed  CAS  Google Scholar 

  28. Meltzer HY, Cola PA, Parsa M. Marked elevations of serum creatine kinase activity associated with antipsychotic drug treatment. Neuropsychopharmacology 1996 Oct; 15(4): 395–405

    Article  PubMed  CAS  Google Scholar 

  29. Rosebush P, Stewart T. A prospective analysis of 24 episodes of neuroleptic malignant syndrome. Am J Psychiatry 1989 Jun; 146(6): 295–8

    Google Scholar 

  30. Shalev A, Munitz H. The neuroleptic malignant syndrome: agent and host interaction. Acta Psychiatr Scand 1986; 73: 337–47

    Article  PubMed  CAS  Google Scholar 

  31. Yamawaki S, Yano E, Uchitomi Y Analysis of 497 cases of neuroleptic malignant syndrome in Japan. Hiroshima J Anesth 1990; 26: 35–44

    Google Scholar 

  32. Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am 1993; 77: 185–202

    PubMed  CAS  Google Scholar 

  33. Keck PE, Pope HG, McElroy SL. Frequency and presentation of neuroleptic malignant syndrome: a prospective study. Am J Psychiatry 1987; 144: 1344–6

    PubMed  Google Scholar 

  34. White DAC, Robins AH. Catatonia: harbinger of the neuroleptic malignant syndrome. Br J Psychiatry 1991; 158: 419–21

    Article  PubMed  CAS  Google Scholar 

  35. White DAC. Catatonia and the neuroleptic malignant syndrome: a single entity? Br J Psychiatry 1992; 161: 558–60

    Article  PubMed  CAS  Google Scholar 

  36. Woodbury MM, Woodbury MA. Neuroleptic-induced catatonia as a stage in the progression toward neuroleptic malignant syndrome. J Am Acad Child Adolesc Psychiatry 1992; 31: 1161–4

    Article  PubMed  CAS  Google Scholar 

  37. Jauss M, Krack P, Franz M, et al. Imaging of Dopamine receptors with [1–123] iodobenzamide single-photon emission-computed tomography in neuroleptic malignant syndrome. Mov Disord 1996 Nov; 11(6): 726–8

    Article  PubMed  CAS  Google Scholar 

  38. Velamoor VR, Swamy MB, Parmar MB, et al. Management of suspected neuroleptic malignant syndrome. Can J Psychiatry 1995; 40: 545–8

    PubMed  CAS  Google Scholar 

  39. Levenson DF, Simpson GM. Neuroleptic-induced extrapyramidal symptoms with fever: heterogeneity of the neuroleptic malignant syndrome. Arch Gen Psychiatry 1986; 43: 839–48

    Article  Google Scholar 

  40. Sewell D, Jeste DV. Distinguishing neuroleptic malignant syndrome (NMS) from NMS-like acute medical illnesses: a study of 34 cases. J Neuropsychiatry 1992; 4(3): 265–9

    CAS  Google Scholar 

  41. Raja M, Altavista MC, Cavallari S, et al. Neuroleptic malignant syndrome and catatonia. Eur Arch Psychiatry Clin Neurosci 1994; 243: 299–303

    Article  PubMed  CAS  Google Scholar 

  42. Bernstein RA. Malignant neuroleptic syndrome: an atypical case. Psychosomatics 1979; 20: 840–6

    PubMed  CAS  Google Scholar 

  43. Misiaszek JJ, Potter RL. Atypical neuroleptic malignant syndrome responsive to conservative management. Psychosomatics 1985; 26: 62–6

    Article  PubMed  CAS  Google Scholar 

  44. Goldman SA. FDA medwatch report - lithium and neuroleptics in combination — the spectrum of neurotoxicity. Psychopharmacol Bull 1996; 32(3): 299–309

    PubMed  CAS  Google Scholar 

  45. Martin TG. Serotonin syndrome. Ann Emerg Med 1996; 28(5): 520–6

    Article  PubMed  CAS  Google Scholar 

  46. Northoff G. Neuroleptic malignant syndrome and catatonia —one entity or two. Biol Psychiatry 1996 Sep; 40(5): 431–2

    Article  PubMed  CAS  Google Scholar 

  47. Blumer D. Catatonia and the neuroleptics — psychobiologic significance of remote and recent findings. Compr Psychiatry 1997 Jul–Aug; 38(4): 193–201

    Article  PubMed  CAS  Google Scholar 

  48. Fricchione G, Bush G, Fozdar M, et al. Recognition and treatment of the catatonic syndrome [review]. J Intens Care Med 1997 May–Jun; 12(3): 135–47

    Google Scholar 

  49. Castillo E, Rubin RT, Holsboer-Trachsler E. Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome. Am J Psychiatry 1989 Mar; 146(3): 324–8

    PubMed  CAS  Google Scholar 

  50. Mann SC, Caroff SN, Bleier HR, et al. Lethal catatonia. Am J Psychiatry 1986; 143: 1374–81

    PubMed  CAS  Google Scholar 

  51. Kellam AMP. The neuroleptic malignant syndrome, so called: a survey of the world literature. Br J Psychiatry 1987; 150: 752–9

    Article  PubMed  CAS  Google Scholar 

  52. Topka H, Buchkremer G. Lethal catatonia, malignant neuroleptic malignant syndrome and myositis ossificans. Nervenarzt 1996 May; 67(5): 413–7

    PubMed  CAS  Google Scholar 

  53. Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome: review. J Clin Psychopharmacol 1997; 17(3); 208–21

    Article  PubMed  CAS  Google Scholar 

  54. Sporer KA. The serotonin syndrome: implicated drugs, pathophysiology and management. Drug Saf 1995; 13: 94–104

    Article  PubMed  CAS  Google Scholar 

  55. Caley CF. Extrapyramidal reactions and the selective serotonin-reuptake inhibitors. Ann Pharmacother 1997; 31: 1481–9

    PubMed  CAS  Google Scholar 

  56. Shalev A, Hermesh H, Munitz H. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry 1989; 50: 18–25

    PubMed  CAS  Google Scholar 

  57. Sakkas P, Davis JM, Hua J, et al. Pharmacotherapy of neuroleptic malignant syndrome. Psychiatr Ann 1991; 21: 157–64

    Google Scholar 

  58. Sakkas P, Davis JM, Janucak PG, et al. Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol Bull 1991; 27: 381–4

    PubMed  CAS  Google Scholar 

  59. Scheftner WA, Shulman RB. Treatment choice in neuroleptic malignant syndrome. Convuls Ther 1992; 8(4): 267–79

    PubMed  Google Scholar 

  60. Davis JM, Janicak PG, Sakkas P, et al. Electroconvulsive therapy in the treatment of the neuroleptic malignant syndrome. Convuls Ther 1991; 7: 111–20

    PubMed  Google Scholar 

  61. Mann SC, Caroff SN, Bleier HR, et al. Electroconvulsive therapy of the lethal catatonia syndrome: case report and review. Convuls Ther 1990; 6: 239–47

    PubMed  Google Scholar 

  62. Lazarus A, Mann SC, Caroff SN. The neuroleptic malignant syndrome and related conditions. Washington, DC: American Psychiatric Press Inc., 1989

    Google Scholar 

  63. Jacobson JL, Jacobson AM. Psychiatric secrets. Philadelphia: Hanley and Belfus Inc., 1996: 466

    Google Scholar 

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  1. Emergency Psychiatry Program, London Health Science Centre, Victoria Campus, 375 South Street, London, Ontario, N6A 4G5, Canada

    Varadaraj R. Velamoor

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Velamoor, V.R. Neuroleptic Malignant Syndrome. Drug-Safety 19, 73–82 (1998). https://doi.org/10.2165/00002018-199819010-00006

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