Neuroleptic malignant syndrome (NMS) is a disorder characterized by autonomic dysfunction, extrapyramidal dysfunction, and hyperthermia and occurs secondary to the use of certain medications most notably neuroleptic drugs. Young and middle-aged adults are more commonly affected although milder forms of this disorder may go unrecognized in the elderly population. Male patients suffer a twofold higher incidence of this disorder than females. This syndrome often begins hours to days after initiating therapy with or increasing the dosage of the medications responsible. The mortality rate has been stated to be as high as 20%, but other reports are as low as 4% especially when the condition is recognized early and supportive care is instituted promptly.

Clinically, this disorder is characterized by hyperthermia, rigidity of varying degrees, an altered mental status, and autonomic dysfunction (hyper or hypotension, tachycardia, tachypnea, hypoxia, diaphoresis, sialorrhea, tremor, and incontinence). Laboratory abnormalities are nonspecific, but leukocytosis and an elevated serum creatinine kinase are usually noted. Rhabdomyolysis and myoglobinuria are potential complications when there is an associated elevation of the serum creatinine kinase. The presence of leukocytosis should prompt an infectious disease workup even when the diagnosis is secure so as not to miss an underlying infection (meningitis, pneumonia, urinary tract infection, etc.). Lethal catatonia should also be considered in the differential diagnosis, and when the symptoms are shivering, head turning, and rigidity of the legs more than the arms, serotonin syndrome is the more likely etiology. Many different systems of diagnostic criteria have been established but hyperthermia and rigidity are two main criteria common to all lists. Complications of this disorder include: respiratory failure, cardiac arrhythmias, acidosis, hyperkalemia, aspiration pneumonia, deep venous thrombosis, pulmonary emboli, rhabdomyolysis, disseminated intravascular coagulation, adult respiratory distress syndrome, and acute renal failure.

The first step in therapy is abrupt withdrawal of the offending agent. Physical cooling measures may prove effective when hyperthermia is severe. Hospitalization in an ICU setting with aggressive supportive care is important. Studies on further therapy are limited, but several references mention the following therapies: bromocriptine (2.5-20 mg PO TID), amantadine (100-200 mg PO BID) and levodopa-carbidopa (TID to QID). With bromocriptine seeming to be the most common first choice. Dantrolene (1-3 mg/kg IV or PO Q8 hours) may be added for muscle relaxation when there is severe rigidity. Benzodiazepines may be substituted for the treatment of agitation during the acute event. Antipsychotic agents that precipitated the event should be held for at least 2 weeks after symptoms resolve, and if needed, restarted cautiously and at a lower dosage.