Neuroleptic malignant syndrome is characterized by altered mental status, muscle rigidity, hyperthermia, and autonomic hyperactivity that occur when certain neuroleptic drugs are used. Clinically, neuroleptic malignant syndrome resembles malignant hyperthermia. Diagnosis is clinical. Treatment is aggressive supportive care.
Among patients taking neuroleptic drugs, about 0.02 to 3% develop neuroleptic malignant syndrome. Patients of all ages can be affected.
Many antipsychotics and antiemetics can be causative (see Table 3: Heat Illness: 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 and Signs
Symptoms begin most often during the first 2 wk of treatment but may occur earlier or after many years.
The 4 characteristic symptoms usually develop over a few days and often in the following order:
The diagnosis 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, BUN, creatinine, glucose, Ca, Mg, and CK, urine myoglobin, and usually neuroimaging and CSF analysis. EEG may be done to exclude nonconvulsive status epilepticus.
The causative drug is stopped and complications are treated supportively, usually in an ICU. Severe hyperthermia is treated very aggressively, mainly with physical cooling (see Heat Illness: Treatment). Some patients may require tracheal intubation 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 q 6 to 12 h; maximum of 10 mg/kg/24 h) can be given for hyperthermia. Bromocriptine (2.5 mg q 6 to 8 h) or, alternatively, amantadine (100 to 200 mg q 12 h) can be given po or via NGT 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%.
Last full review/revision February 2010 by James P. Knochel, MD
Content last modified February 2012