Neuroleptic Malignant Syndrome

Many antipsychotics and antiemetics can be causative (see table Drugs That Can Cause Neuroleptic Malignant Syndrome ). The factor common to all drug causes is a decrease in dopaminergic transmission; however, the reaction is not allergic but rather idiosyncratic. Etiology and mechanism are unknown. Risk factors appear to include high drug doses, rapid dose increases, parenteral administration, and switching from one potentially causative drug to another.

Neuroleptic malignant syndrome can also occur in patients withdrawing from levodopa or dopamine agonists.

Symptoms of neuroleptic malignant syndrome begin most often during the first 2 weeks of treatment with neuroleptic drugs but may occur earlier or after many years.

The 4 characteristic symptoms usually develop over a few days and often in the following order:

Neuroleptic malignant syndrome should be suspected based on clinical findings. Early manifestations can be missed because mental status changes may be overlooked or dismissed in patients with psychosis.

Other disorders can cause similar findings. For example:

There are no confirmatory tests, but patients should have testing for complications, including serum electrolytes, blood urea nitrogen, creatinine, glucose, calcium, magnesium, and creatine kinase, urine myoglobin, and usually neuroimaging and cerebrospinal fluid analysis.

In patients with neuroleptic malignant syndrome, the causative drug is stopped and complications are treated supportively, usually in an intensive care unit (ICU) (1 Key Points Neuroleptic malignant syndrome is characterized by altered mental status, muscle rigidity, hyperthermia, and autonomic hyperactivity that occur when certain neuroleptic drugs are used. Clinically... read more ). Severe hyperthermia is treated aggressively, mainly with physical cooling (see Heatstroke: Treatment Treatment Heatstroke is hyperthermia accompanied by a systemic inflammatory response causing multiple organ dysfunction that may result in death. Symptoms include temperature > 40° C and altered mental... read more ). Some patients may require tracheal intubation (see Airway Establishment and Control/Tracheal Intubation Tracheal Intubation Most patients requiring an artificial airway can be managed with tracheal intubation, which can be Orotracheal (tube inserted through the mouth) Nasotracheal (tube inserted through the nose)... read more ) and induced coma. Benzodiazepines, given IV in high doses, can be used to control agitation. Adjunctive drug therapy can be used, although efficacy has not been shown in clinical trials. Dantrolene 0.25 to 2 mg/kg IV every 6 to 12 hours to a maximum of 10 mg/kg/24 hours can be given for hyperthermia. Bromocriptine 2.5 mg every 6 to 8 hours or, alternatively, amantadine 100 to 200 mg every 12 hours can be given orally or via nasogastric tube to help restore some dopaminergic activity. This condition may not respond to even rapid and aggressive therapy, and mortality in treated cases is about 10 to 20%.