Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'

Arch Gen Psychiatry. 1986 Sep;43(9):839-48. doi: 10.1001/archpsyc.1986.01800090025005.


From 39 reported cases of the "neuroleptic malignant syndrome," three groups were identified: those with concurrent medical problems that could cause fever that accompanied the extrapyramidal symptoms; those with medical problems less clearly related to fever; and those without other medical disorders. Dehydration, infection, pulmonary embolus, and rhabdomyolysis were the common complications of untreated extrapyramidal symptoms. Three patients died, all with medical complications. In 14 cases, no medical cause of fever was identified. Hypotheses about mechanisms for fever include psychiatric illness, disruption of dopaminergic aspects of thermoregulation, and peripheral and central effects on muscle contraction leading to excess heat production. Neuroleptic-induced rigidity should be treated vigorously, with prompt discontinuation of neuroleptic therapy and administration of dopamine agonists in severe cases with or without fever. The cases of extrapyramidal symptoms with fever are too heterogeneous to justify the assumption of a unitary and "malignant" syndrome.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / adverse effects*
  • Basal Ganglia Diseases / chemically induced*
  • Basal Ganglia Diseases / diagnosis
  • Basal Ganglia Diseases / mortality
  • Body Temperature Regulation / drug effects
  • Catatonia / diagnosis
  • Catatonia / mortality
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Female
  • Fever / chemically induced*
  • Fever / diagnosis
  • Fever / mortality
  • Humans
  • Male
  • Middle Aged
  • Muscle Contraction / drug effects
  • Neuroleptic Malignant Syndrome / diagnosis*
  • Neuroleptic Malignant Syndrome / mortality
  • Receptors, Dopamine / drug effects


  • Antipsychotic Agents
  • Receptors, Dopamine