Some cases of NMS are milder than those in published reports, which may reflect a greater awareness of the risk for this syndrome and more prompt intervention. However, it is possible that NMS manifests in a spectrum of clinical severity.
Mortality associated with NMS appears to vary.[3]Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am. 1993 Jan;77(1):185-202.
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[5]Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatry. 1998 Aug;155(8):1113-6.
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[6]Levinson DF, Simpson GM. Neuroleptic-induced extrapyramidal symptoms with fever: heterogeneity of the 'neuroleptic malignant syndrome'. Arch Gen Psychiatry. 1986 Sep;43(9):839-48.
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[14]Gurrera RJ, Simpson JC, Tsuang MT. Meta-analytic evidence of systematic bias in estimates of neuroleptic malignant syndrome incidence. Compr Psychiatry. 2007 Mar-Apr;48(2):205-11.
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[19]Pope HG Jr, Keck PE Jr, McElroy SL. Frequency and presentation of neuroleptic malignant syndrome in a large psychiatric hospital. Am J Psychiatry. 1986 Oct;143(10):1227-33.
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[20]Keck PE Jr, Pope HG Jr, McElroy SL. Declining frequency of neuroleptic malignant syndrome in a hospital population. Am J Psychiatry. 1991 Jul;148(7):880-2.
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[21]Neuhut R, Lindenmayer JP, Silva R. Neuroleptic malignant syndrome in children and adolescents on atypical antipsychotic medication: a review. J Child Adolesc Psychopharmacol. 2009 Aug;19(4):415-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861947
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Two large studies reported a rate between 8% and 9%.[16]Nielsen RE, Wallenstein Jensen SO, et al. Neuroleptic malignant syndrome - an 11-year longitudinal case-control study. Can J Psychiatry. 2012 Aug;57(8):512-8.
http://www.ncbi.nlm.nih.gov/pubmed/22854034?tool=bestpractice.com
[22]Nakamura M, Yasunaga H, Miyata H, et al. 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 Apr;73(4):427-30.
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A subsequent systematic review found that respiratory difficulties, hyperthermia severity, and older age were associated with increased mortality.[23]Guinart D, Misawa F, Rubio JM, et al. A systematic review and pooled, patient-level analysis of predictors of mortality in neuroleptic malignant syndrome. Acta Psychiatr Scand. 2021 Oct;144(4):329-41.
http://www.ncbi.nlm.nih.gov/pubmed/34358327?tool=bestpractice.com
Recurrence of NMS has been estimated to be as high as 30%, but there are no reliable data regarding recurrence.[3]Caroff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North Am. 1993 Jan;77(1):185-202.
http://www.ncbi.nlm.nih.gov/pubmed/8093494?tool=bestpractice.com
It is usually recommended that rechallenge be postponed until at least 2 weeks after complete resolution of the syndrome.[52]Velamoor VR. Neuroleptic malignant syndrome. Recognition, prevention and management. Drug Saf. 1998 Jul;19(1):73-82.
https://www.doi.org/10.2165/00002018-199819010-00006
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Rechallenge should proceed slowly and under close monitoring, including appropriate laboratories.[1]Strawn JR, Keck PE Jr, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007 Jun;164(6):870-6.
http://www.ncbi.nlm.nih.gov/pubmed/17541044?tool=bestpractice.com