Neuroleptic Malignant Syndrome

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.