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Neuroleptic malignant syndrome

Eelco FM Wijdicks, MD
Section Editor
Michael J Aminoff, MD, DSc
Deputy Editor
Janet L Wilterdink, MD


Neuroleptic malignant syndrome (NMS) is a life threatening neurologic emergency associated with the use of neuroleptic agents and characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia.

Mortality results directly from the dysautonomic manifestations of the disease and from systemic complications. Mortality has declined from the earliest reports in the 1960s of 76 percent and is more recently estimated between 10 and 20 percent [1]. This probably reflects greater awareness of the disease, earlier diagnosis, and more aggressive intervention. Requiring a high clinical suspicion for diagnosis and treatment, NMS is appropriately a syndrome more often considered than truly diagnosed.


Incidence rates for neuroleptic malignant syndrome (NMS) range from 0.02 to 3 percent among patients taking neuroleptic agents [2,3]. This wide range probably reflects differences in the populations sampled, for example, inpatient versus outpatient psychiatric populations, as well as differences in the surveillance methods and definitions of disease used.

While most patients with NMS are young adults, the syndrome has been described in all age groups from 0.9 to 78 years [2,4-6]. Age is not a risk factor [7]. In most studies, men outnumber women twofold. Both age and gender distributions correspond with the distribution of the exposure to neuroleptic agents [4,7].


Neuroleptic agents — NMS is most often seen with the "typical" high potency neuroleptic agents (eg, haloperidol, fluphenazine) [8-10]. However, every class of neuroleptic drug has been implicated, including the low potency (eg, chlorpromazine) and the newer "atypical" antipsychotic drugs (eg, clozapine, risperidone, olanzapine) as well as antiemetic drugs (eg, metoclopramide, promethazine) [4,11]. Associated medications are listed in the Table (table 1).


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Literature review current through: May 2017. | This topic last updated: May 30, 2014.
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