neuroleptic malignant syndrome


Summary: A potentially fatal syndrome associated primarily with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS) which are in turn associated with dopaminergic receptor blockade (see RECEPTORS, DOPAMINE) in the BASAL GANGLIA and HYPOTHALAMUS, and sympathetic dysregulation. Clinical features include diffuse MUSCLE RIGIDITY; TREMOR; high FEVER; diaphoresis; labile blood pressure; cognitive dysfunction; and autonomic disturbances. Serum CPK level elevation and a leukocytosis may also be present. (From Adams et al., Principles of Neurology, 6th ed, p1199; Psychiatr Serv 1998 Sep;49(9):1163-72)

Top Publications

  1. Ozer F, Meral H, Aydin B, Hanoglu L, Aydemir T, Oral T. Electroconvulsive therapy in drug-induced psychiatric states and neuroleptic malignant syndrome. J ECT. 2005;21:125-7 pubmed
    ..A patient with Parkinson disease, major depression, and paranoid psychosis who developed neuroleptic malignant syndrome (NMS) as the result of the sudden termination of high-dose (1200 mg/d) levodopa treatment is presented ..
  2. van Maldegem B, Smit L, Touw D, Gemke R. Neuroleptic malignant syndrome in a 4-year-old girl associated with alimemazine. Eur J Pediatr. 2002;161:259-61 pubmed
    b>Neuroleptic malignant syndrome (NMS) is a rare but serious disorder caused by antipsychotic medication including phenothiazines...
  3. Carroll B, Lee J. Catatonia is a risk factor for neuroleptic malignant syndrome. J Clin Psychiatry. 2004;65:1722-3 pubmed
  4. Randolph T. Possible contribution of XYY syndrome to neuroleptic malignant syndrome in a child receiving quetiapine. Am J Health Syst Pharm. 2010;67:459-61 pubmed publisher
    A case of early neuroleptic malignant syndrome (NMS) in a child with XYY syndrome after three weeks of quetiapine therapy is reported.
  5. Dew R, Rosenquist P, McCall W. Aripiprazole for agitation in a 13-year-old girl with neuroleptic malignant syndrome. Int J Adolesc Med Health. 2005;17:187-8 pubmed
    b>Neuroleptic Malignant Syndrome (NMS) rarely results from atypical antipsychotic therapy. To date, no information is available on the incidence of NMS with aripiprazole, a newer neuroleptic.
  6. Duggal H, Kithas J. Possible neuroleptic malignant syndrome with aripiprazole and fluoxetine. Am J Psychiatry. 2005;162:397-8 pubmed
  7. Reulbach U, Dütsch C, Biermann T, Sperling W, Thuerauf N, Kornhuber J, et al. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care. 2007;11:R4 pubmed
    b>Neuroleptic malignant syndrome (NMS) is a rare, but sometimes fatal, adverse reaction to neuroleptics characterized principally by fever and rigor...
  8. Kobayashi A, Kawanishi C, Matsumura T, Kato D, Furukawa R, Kishida I, et al. Quetiapine-induced neuroleptic malignant syndrome in dementia with Lewy bodies: a case report. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1170-2 pubmed
    ..The present report is the first to describe a DLB patient who developed neuroleptic malignant syndrome (NMS) induced by quetiapine, an atypical neuroleptic known to have relatively infrequent ..
  9. Kawanishi C, Onishi H, Kato D, Yamada T, Onose M, Hirayasu Y. Neuroleptic malignant syndrome in cancer treatment. Palliat Support Care. 2005;3:51-3 pubmed
    b>Neuroleptic malignant syndrome (NMS) is a life-threatening reaction to neuroleptics. Several prospective studies have reported NMS occurrence rates ranging from 0.07% to 2.2% of patients receiving neuroleptics...

More Information


  1. Borovicka M, Bond L, Gaughan K. Ziprasidone- and lithium-induced neuroleptic malignant syndrome. Ann Pharmacother. 2006;40:139-42 pubmed
    To report a case of ziprasidone- and lithium-induced neuroleptic malignant syndrome (NMS).
  2. Uguz F, Sonmez E. Neuroleptic malignant syndrome following combination of sertraline and paroxetine: a case report. Gen Hosp Psychiatry. 2013;35:327.e7-327.e8 pubmed publisher
    b>Neuroleptic malignant syndrome (NMS) is a rarely observed life-threatening medical condition due mostly to antipsychotic use...
  3. Odagaki Y. Atypical neuroleptic malignant syndrome or serotonin toxicity associated with atypical antipsychotics?. Curr Drug Saf. 2009;4:84-93 pubmed a patient taking medication including atypical antipsychotics, it has tended to be diagnosed as neuroleptic malignant syndrome (NMS)...
  4. Mendhekar D, Jiloha R. Neuroleptic malignant syndrome precipitated by haloperidol following clozapine discontinuation. Aust N Z J Psychiatry. 2005;39:947-8 pubmed
  5. Spalding S, Alessi N, Radwan K. Aripiprazole and atypical neuroleptic malignant syndrome. J Am Acad Child Adolesc Psychiatry. 2004;43:1457-8 pubmed
  6. Kawanishi C. Genetic predisposition to neuroleptic malignant syndrome : implications for antipsychotic therapy. Am J Pharmacogenomics. 2003;3:89-95 pubmed
    The pathogenetic mechanism of neuroleptic malignant syndrome (NMS), a potentially lethal adverse effect of antipsychotics, is not well understood...
  7. Kishida I, Kawanishi C, Furuno T, Kato D, Ishigami T, Kosaka K. Association in Japanese patients between neuroleptic malignant syndrome and functional polymorphisms of the dopamine D(2) receptor gene. Mol Psychiatry. 2004;9:293-8 pubmed
    A genetic predisposition to the development of neuroleptic malignant syndrome (NMS) has been suggested by clinical studies...
  8. Northoff G. Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology. J Neural Transm (Vienna). 2002;109:1453-67 pubmed
    ..Since neuroleptics can induce catatonic-like symptoms i.e. neuroleptic malignant syndrome (NMS), there has been a recent re-emergence in clinical and scientific interest in catatonia...
  9. Trollor J, Chen X, Chitty K, Sachdev P. Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics. Br J Psychiatry. 2012;201:52-6 pubmed publisher
    Reports of neuroleptic malignant syndrome (NMS) induced by second-generation antipsychotic drugs highlight a propensity for atypical clinical presentations...
  10. Musselman M, Browning L, Parker D, Saely S. Neuroleptic malignant syndrome associated with the use of prochlorperazine in a patient with a recent history of antipsychotic-induced neuroleptic malignant syndrome. Ann Pharmacother. 2011;45:e61 pubmed publisher
    To describe a case of neuroleptic malignant syndrome (NMS) associated with the use of prochlorperazine in a patient recently hospitalized for NMS secondary to olanzapine.
  11. Ochi S, Kawasoe K, Abe M, Fukuhara R, Sonobe K, Kawabe K, et al. A case study: neuroleptic malignant syndrome with risperidone and CYP2D6 gene variation. Gen Hosp Psychiatry. 2011;33:640.e1-2 pubmed publisher
    We present a schizophrenic patient who experienced neuroleptic malignant syndrome with risperidone treatment due to variants of the CYP2D6 gene with reduced function. Clinicians need to be aware of this potential complication.
  12. Gallelli L, Spagnuolo V, Palleria C, De Sarro G, Ferraro M. A case of neuroleptic malignant syndrome induced by risperidone in a schizophrenic woman. Curr Drug Saf. 2009;4:119-20 pubmed
    We report a case of neuroleptic malignant syndrome in a woman who assumed risperidone for schizoaffective disorders.
  13. Asakura Y, Fujiwara Y, Komatsu T. The WHO analgesic ladder and neuroleptic malignant syndrome. Acta Anaesthesiol Scand. 2006;50:1311-2 pubmed
  14. Paparrigopoulos T, Tzavellas E, Ferentinos P, Mourikis I, Liappas J. Catatonia as a risk factor for the development of neuroleptic malignant syndrome: report of a case following treatment with clozapine. World J Biol Psychiatry. 2009;10:70-3 pubmed publisher
    ..abnormalities and shares many clinical, biological and treatment response features with the neuroleptic malignant syndrome (NMS), a rare adverse reaction to psychoactive medications...
  15. Franzen D, Burkhard J, Corti N, Schüpbach D, Fontanel D, Staubli M. [Neuroleptic malignant syndrome after 30 years treatment with clozapine: a rarely seen differential diagnosis on intensive care units]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2006;41:125-7 pubmed
    The neuroleptic malignant syndrome (NMS) is a rare, but potentially lethal side effect of conventional and atypical antipsychotic drugs...
  16. Srephichit S, Sanchez R, Bourgeois J. Neuroleptic malignant syndrome and aripiprazole in an antipsychotic-naive patient. J Clin Psychopharmacol. 2006;26:94-5 pubmed
  17. Norgard N, Stark J. Olanzapine-associated neuroleptic malignant syndrome. Pharmacotherapy. 2006;26:1180-2 pubmed
    b>Neuroleptic malignant syndrome (NMS) is a rare but potentially serious complication of neuroleptic drugs. It may vary in both presenting characteristics and severity...
  18. Malyuk R, Gibson B, Procyshyn R, Kang N. Olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome: case report. Int J Geriatr Psychiatry. 2002;17:326-8 pubmed
    We describe here a case of olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome in a 64 year-old woman with a significant medical history...
  19. Kopf A, Köster J, Schulz A, Krömker H, Becker T. [Life threatening neuroleptic malignant syndrome due to olanzapine]. Psychiatr Prax. 2003;30:279-82 pubmed
    The frequency of neuroleptic malignant syndrome (NMS) after clozapine or olanzapine is low and often of non-serious nature. A 49 year-old female patient developed NMS 12 days after olanzapine re-exposure...
  20. Kontaxakis V, Havaki Kontaxaki B, Christodoulou N, Paplos K. Olanzapine-associated neuroleptic malignant syndrome. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:897-902 pubmed
    b>Neuroleptic malignant syndrome (NMS) is an uncommon but serious idiosyncratic reaction associated with antipsychotic medication...
  21. Tsai J, Yang P, Yen J, Chen C, Yang M. Zotepine-induced catatonia as a precursor in the progression to neuroleptic malignant syndrome. Pharmacotherapy. 2005;25:1156-9 pubmed
    ..b>Neuroleptic malignant syndrome (NMS) was diagnosed...
  22. Viejo L, Morales V, Puñal P, Perez J, Sancho R. Risk factors in neuroleptic malignant syndrome. A case-control study. Acta Psychiatr Scand. 2003;107:45-9 pubmed
    To determine whether environmental temperature, agitation, neuroleptic use, mental retardation, and affective disorders were risk factors for neuroleptic malignant syndrome (NMS).
  23. Bhanushali M, Tuite P. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin. 2004;22:389-411 pubmed
    ..Definitive treatment guidelines remain an important issue to be addressed. Efforts have been initiated in that direction and all cases can be reported on a toll-free hotline ( 1-888-667-8367) or online (
  24. Chakraborty N, Johnston T. Aripiprazole and neuroleptic malignant syndrome. Int Clin Psychopharmacol. 2004;19:351-3 pubmed our first patient to receive this drug, who had treatment-resistant schizophrenia and developed neuroleptic malignant syndrome (NMS) with aripiprazole...
  25. Zalsman G, Lewis R, Konas S, Loebstein O, Goldberg P, Burguillo F, et al. Atypical neuroleptic malignant syndrome associated with risperidone treatment in two adolescents. Int J Adolesc Med Health. 2004;16:179-82 pubmed
    b>Neuroleptic Malignant Syndrome (NMS) is a known, life threatening, side effect of classical antipsychotic drugs...
  26. Gambassi G, Capurso S, Tarsitani P, Liperoti R, Bernabei R. Fatal neuroleptic malignant syndrome in a previously long-term user of clozapine following its reintroduction in combination with paroxetine. Aging Clin Exp Res. 2006;18:266-70 pubmed
    ..The diagnosis of neuroleptic malignant syndrome was delayed, because there was no leukocytosis and serum creatine phosphokinase was initially not ..
  27. Rais A, Kimmel S, Shrestha N, Rais T, Coffey B. Atypical neuroleptic malignant syndrome in an adolescent. J Child Adolesc Psychopharmacol. 2008;18:215-20 pubmed publisher
  28. Bourgeois J, Babine S, Meyerovich M, Doyle J. A case of neuroleptic malignant syndrome with quetiapine. J Neuropsychiatry Clin Neurosci. 2002;14:87 pubmed
  29. Lewis A, Pelic C, Kahn D. Malignant catatonia in a patient with bipolar disorder, B12 deficiency, and neuroleptic malignant syndrome: one cause or three?. J Psychiatr Pract. 2009;15:415-22 pubmed publisher
    ..Her condition rapidly worsened to a state consistent with either neuroleptic malignant syndrome or malignant catatonia...
  30. Sato T, Nishio H, Iwata M, Kentotsuboi -, Tamura A, Miyazaki T, et al. Postmortem molecular screening for mutations in ryanodine receptor type 1 (RYR1) gene in psychiatric patients suspected of having died of neuroleptic malignant syndrome. Forensic Sci Int. 2010;194:77-9 pubmed publisher
    Postmortem diagnosis of neuroleptic malignant syndrome (NMS) is difficult to perform, because the clinical symptoms just before death are not usually available...
  31. Margetic B, Aukst Margetic B. Neuroleptic malignant syndrome and its controversies. Pharmacoepidemiol Drug Saf. 2010;19:429-35 pubmed publisher
    b>Neuroleptic malignant syndrome (NMS) is a rare and life threatening condition usually defined as a complication of treatment with antipsychotics characterized by severe rigidity, tremor, fever, altered mental status, autonomic dysfunction,..
  32. Chen Y, Guo J, Steinbuch M, Buckley P, Patel N. Risk of neuroleptic malignant syndrome in patients with bipolar disorder: a retrospective, population-based case-control study. Int J Psychiatry Med. 2009;39:439-50 pubmed
    Current data regarding risk factors of neuroleptic malignant syndrome (NMS) are limited. This study aims to examine factors associated with increased risk of NMS in patients with bipolar disorder.
  33. Gurrera R, Caroff S, Cohen A, Carroll B, DeRoos F, Francis A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry. 2011;72:1222-8 pubmed publisher
    The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications...
  34. Nielsen R, Wallenstein Jensen S, Nielsen J. Neuroleptic malignant syndrome-an 11-year longitudinal case-control study. Can J Psychiatry. 2012;57:512-8 pubmed
    To describe patients with neuroleptic malignant syndrome (NMS), to establish occurrence of NMS, to investigate risk factors of NMS, and to investigate mortality associated with NMS.
  35. Mendhekar D, Duggal H. Persistent amnesia as a sequel of olanzapine-induced neuroleptic malignant syndrome. J Neuropsychiatry Clin Neurosci. 2006;18:552-3 pubmed
  36. Leibold J, Patel V, Hasan R. Neuroleptic malignant syndrome associated with ziprasidone in an adolescent. Clin Ther. 2004;26:1105-8 pubmed
    b>Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disorder characterized by fever, muscular rigidity, delirium, and autonomic instability...
  37. Mihara K, Kondo T, Suzuki A, Yasui Furukori N, Ono S, Sano A, et al. Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome. Am J Med Genet B Neuropsychiatr Genet. 2003;117B:57-60 pubmed
    ..the TaqI A polymorphism of dopamine D2 receptor gene (DRD2) is associated with the predisposition to neuroleptic malignant syndrome (NMS)...
  38. Kadyan V, Colachis S, Depalma M, Sanderson J, Mysiw W. Early recognition of neuroleptic malignant syndrome during traumatic brain injury rehabilitation. Brain Inj. 2003;17:631-7 pubmed
    b>Neuroleptic malignant syndrome is a rare disorder that manifests with hyperthermia, muscle rigidity and autonomic instability...
  39. Gray N. Ziprasidone-related neuroleptic malignant syndrome in a patient with Parkinson's disease: a diagnostic challenge. Hum Psychopharmacol. 2004;19:205-7 pubmed
    A case of neuroleptic malignant syndrome (NMS) in a patient with Parkinson's disease (PD) is presented. The syndrome was precipitated by the atypical antipsychotic, ziprasidone...
  40. Mishra B, Mishra B, Sahoo S, Arora M, Khess C. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine. Indian J Med Sci. 2007;61:570-3 pubmed
    b>Neuroleptic malignant syndrome (NMS) is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of ..
  41. Rosebush P, Garside S, Mazurek M. Recognizing neuroleptic malignant syndrome. CMAJ. 2004;170:1645 pubmed
  42. Nakamura M, Yasunaga H, Miyata H, Shimada T, Horiguchi H, Matsuda S. Mortality of neuroleptic malignant syndrome induced by typical and atypical antipsychotic drugs: a propensity-matched analysis from the Japanese Diagnosis Procedure Combination database. J Clin Psychiatry. 2012;73:427-30 pubmed publisher
    b>Neuroleptic malignant syndrome induced by atypical antipsychotics presents atypical clinical manifestations with fewer symptoms compared with neuroleptic malignant syndrome induced by typical antipsychotics...
  43. Sugden S, Bourgeois J, Kile S, Hilty D. Neuroleptic malignant syndrome with dermatologic complications. J Clin Psychopharmacol. 2004;24:676-8 pubmed
  44. Atbasoglu E, Ozguven H, Can Saka M, Goker C. Rhabdomyolysis and coma associated with amisulpride: a probable atypical presentation of neuroleptic malignant syndrome. J Clin Psychiatry. 2004;65:1724-5 pubmed
  45. Gill J, Singh H, Nugent K. Acute lithium intoxication and neuroleptic malignant syndrome. Pharmacotherapy. 2003;23:811-5 pubmed
    ..His creatine kinase level was 698 IU/L, serum creatinine 3.5 mg/dl. Late-onset neuroleptic malignant syndrome (NMS) was diagnosed...
  46. Mantas C, Kalabokis G, Goulia P, Tourlakopoulos A, Hyphantis T, Mavreas V. Possible neuroleptic malignant syndrome during paliperidone administration: a case report. J Clin Psychopharmacol. 2010;30:89-91 pubmed publisher
  47. Del Tacca M, Lattanzi L, Lastella M, Di Paolo A, Mungai F, Danesi R, et al. Genotype A1/A2 associated with neuroleptic malignant syndrome. Bipolar Disord. 2005;7:390-1 pubmed
  48. Caroff S, Campbell E, Sullivan K. Neuroleptic malignant syndrome in elderly patients. Expert Rev Neurother. 2007;7:423-31 pubmed
    ..Among the latter are severe neurological disorders, including neuroleptic malignant syndrome. Although the incidence and mortality of neuroleptic malignant syndrome may have declined with ..
  49. Hall R, Appleby B, Hall R. Atypical neuroleptic malignant syndrome presenting as fever of unknown origin in the elderly. South Med J. 2005;98:114-7 pubmed
    ..After an extensive workup to rule out infection, the patient was diagnosed as having neuroleptic malignant syndrome (NMS)...
  50. Ali S, Pearlman R, Upadhyay A, Patel P. Neuroleptic malignant syndrome with aripiprazole and lithium: a case report. J Clin Psychopharmacol. 2006;26:434-6 pubmed
  51. Berardi D, Dell Atti M, Amore M, De Ronchi D, Ferrari G. Clinical risk factors for neuroleptic malignant syndrome. Hum Psychopharmacol. 2002;17:99-102 pubmed
    Pharmacological risk factors for neuroleptic malignant syndrome (NMS) are better defined than clinical risk factors. We examined the psychopathological status preceding the onset of NMS in 20 patients...
  52. Ananth J, Johnson K, Levander E, Harry J. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004;65:724 pubmed
  53. Srivastava A, Borkar H, Chandak S. Olanzapine-induced neuroleptic malignant syndrome in a patient with paranoid schizophrenia. Psychiatry Clin Neurosci. 2009;63:119-21 pubmed publisher
    A case of a male patient with schizophrenic illness who developed neuroleptic malignant syndrome (NMS) following treatment with olanzapine is reported...