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Incidence of 0.01–0.02%
Mortality rate of 10%
2000 cases of NMS diagnosed annually in USA hospitals
Pharmacologic:
Typical/“first generation” antipsychotic
Rapid dose titration/switching agents/abrupt medication withdrawal/high cumulative dose
IM depot/IV administration
Multiple concurrent antipsychotics or antipsychotic with lithium/carbamazepine
Demographic/miscellaneous:
Advanced age
Psychiatric/medical comorbidities
Anemia
Dehydration/malnutrition
Pt history of NMS
Hot climate/high ambient temperature
Pulm aspiration
Cardiovascular lability
Rhabdomyolysis
Potentially life-threatening if left untreated
Increased risk of recurrence in pts requiring chronic antipsychotic therapy with Hx of previous NMS
Increased off-label use of antipsychotics
Differentiating NMS from serotonin syndrome, malignant hyperthermia, drug-induced extrapyramidal reactions, and substance-abuse withdrawal
Rare, iatrogenic hypermetabolic reaction characterized by fulminant or insidious development of muscular rigidity, altered sensorium, dysautonomia, and high fever.
Triggered by antidopaminergic agents or DA agonist withdrawal.
More common in pts with psychiatric Hx of schizophrenia, schizoaffective disorder, bipolar disorder, mental retardation, Parkinson disease, dementia, and psychosis.
Despite declining frequency likely due to more widespread recognition and earlier diagnosis/treatment, NMS remains a significant source of morbidity and mortality for pts taking antipsychotics.
Shares striking clinical similarities with but is otherwise pathophysiologically distinct from malignant hyperthermia; to date, no definitive evidence demonstrating that NMS increases the risk of malignant hyperthermia under general anesthesia.
Central D 2 receptor antagonism triggers a cascade of disrupted DA receptor–mediated signaling pathways with resultant autonomic dysregulation and end stage hypermetabolic syndrome.
Known triggering scenarios include DA antagonists, DA-agonist withdrawal, and GABA-agonist withdrawal.
Once NMS is diagnosed and the triggering agent discontinued, NMS is generally self-limited, and full resolution can be expected to occur within 1 wk to 10 d, with appropriate supportive therapy.
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