Neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) was first recognized as a life-threatening complication of dopamine receptor antagonists characterized by extrapyramidal disturbances, hyperthermia, and elevated serum creatine kinase levels. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and because syndromes identical to NMS have been observed in patients with Parkinson's disease withdrawn from their medication or suffering akinetic hyperthermic parkinsonian crisis. The neurochemical key features in all these conditions are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino acid neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS is the most important step in its management; the outcome is good if causative drugs are discontinued or if parkinsonian therapy is readjusted. Supportive care includes management of hyperthermia and fluid replacement. Controversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a history of NMS and psychotic relapse necessitating neuroleptic drugs do not commonly redevelop NMS when reexposed to dopamine receptor antagonists but may be treated most safely with atypical neuroleptic drugs such as clozapine.