Neuroleptic malignant syndrome is a rare but dangerous condition seen in patients taking antipsychotic medication. It carries a mortality of up to 10% and can also occur with atypical antipsychotics. It may also occur with dopaminergic drugs (such as levodopa) for Parkinson's disease, usually when the drug is suddenly stopped or the dose reduced.


  • Incidence: 0.50 cases per 100,000 person-years
  • Peak incidence: 40-50 years
  • Sex ratio: more common in males 2:1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+


The pathophysiology is unknown but one theory is that the dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage.

Clinical features

  • watery diarrhoea: usually insidious but more acute presentations are seen
  • faecal urgency and incontinence is a frequent feature
  • abdominal pain
  • constitutional symptoms such as weight loss, lethargy and arthralgia may be present
  • non-specific investigation findings include mild anaemia and raised inflammatory markers. Autoantibodies such as rheumatoid factor and ANA may also be present


A raised creatine kinase is present in most cases. Acute kidney injury (secondary to rhabdomyolysis) may develop in severe cases. A leukocytosis may also be seen

Differential diagnosis

Venn diagram showing contrasting serotonin syndrome with neuroleptic malignant syndrome. Note that both conditions can cause a raised creatine kinase (CK) but it tends to be more associated with NMS.


  • stop antipsychotic
  • patients should be transferred to a medical ward if they are on a psychiatric ward and often they are nursed in intensive care units
  • IV fluids to prevent renal failure
  • dantrolene may be useful in selected cases
    • thought to work by decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulum
  • bromocriptine, dopamine agonist, may also be used