Neuroleptic Malignant Syndrome, with Attention to Its Occurrence with Atypical Antipsychotic Medication: A Review

The neuroleptic malignant syndrome (NMS) is an idiopathic, life-threatening reaction to antipsychotic medication. NMS was traditionally attributed to potent dopamine antagonism of typical antipsychotics, but cases of NMS have now been reported for each of the newer antipsychotics. When NMS is caused by a newer, atypical antipsychotic the presentation differs somewhat; fever, rigidity, and, possibly, death may be less frequent. Diagnostic features, predisposing factors, and treatment are discussed, as is the important matter of reinstituting antipsychotic treatment. Neuroleptic malignant syndrome (NMS) is an idiosyncratic, life-threatening reaction to antipsychotic medication, characterized principally by delirium, fever, autonomic instability, and muscular rigidity (1). Most cases occur within a month of starting the medication, two-thirds within the first week. NMS develops in 0.022.44 percent of patients who are prescribed antipsychotics (2-4); NMS may occur even when doses are in the therapeutic range; the risk is somewhat greater with rapid dose escalation and with parenteral administration. Hyperthermia, delirium, autonomic instability, and extrapyramidal symptoms in a person treated with antipsychotic medications should prompt consideration of NMS. Classically, the extrapyramidal symptoms of NMS manifest as “lead pipe” rigidity of the limbs; other extrapyramidal signs, such as tremor, and cogwheeling, may be present. The muscular rigidity leads to rhabdomyolysis, which can in turn result in renal failure. A wide range of mental status presentations are possible, but patients are most often mute and stuporous. Laboratory findings include leukocytosis (most often 10-20,000, thought to be a stress response) elevated creatine kinase (can reach 100,000), hypocalcemia (from muscle sequestration of calcium), moderate elevations of LDH, AST and ALT, and elevated serum osmolarity from dehydration. An EEG may show generalized slowing, consistent with delirium (5). Symptoms generally develop over 24-72 hours and, in