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Neuroleptic Malignant Syndrome

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Overview

Neuroleptic malignant syndrome (NMS) is an uncommon but life-threatening complication associated with dopamine antagonists, typically antipsychotic (neuroleptic) drugs. It can also happen in patients taking dopaminergic drugs (e.g. for Parkinson’s disease) when the drug is suddenly stopped or the dose is reduced. The underlying pathology is not fully understood.

Epidemiology

  • Incidence has dropped with the availability of newer antipsychotics
  • It can happen at any age

Risk Factors

  • Use of antipsychotic drugs
  • Withdrawal or changes in the dose of Parkinson’s medication
  • Structural brain problems e.g. delirium, dementia, trauma, Wilson’s disease
  • Older age
  • Akathisia
  • Catatonia

Presentation

Symptoms are often after starting or changing the dose of an antipsychotic or stopping a dopaminergic medication, with most cases presenting within ten days. Features arise over hours-days:

  • Hyperthermia (>38°C)
  • Altered mental status – delirium, confusion, or stupor
  • Muscle rigidity
  • Labile autonomic dysfunction:
  • Hyporeflexia
  • Tachycardia
  • Tachypnoea

Differential Diagnoses

Serotonin syndrome

  • History of antidepressant use/ecstasy
  • Onset within hours
  • Dilated pupils – pupils are normal in NMS
  • Clonus
  • Hyperreflexia – hyporeflexia is seen in NMS

Investigations

Neuroleptic malignant syndrome is a diagnosis of exclusion, other causes must be ruled out such as sepsis.

  • Serum creatine kinase (CK):
    • At least 4 times the upper limit of normal
    • If 5 times above the upper limit of normal, there may be rhabdomyolysis
  • ECG in all patients suspected to have NMS:
    • NMS can cause ECG abnormalities 
  • Blood gases:
  • Blood glucose:
    • May be high, low, or normal
  • U&Es and urinalysis:
    • NMS may cause an AKI secondary to rhabdomyolysis
  • FBC:
    • May show leukocytosis
  • LFTs:
    • To exclude liver problems
  • Clotting screen:

Management

Overview

  • 1st-line: stop the antipsychotic/restart the dopamine agonist + IV fluids to prevent AKI and cool
  • If severe and unresponsive to 1st-line measures: consider dantrolene or dopamine agonists (bromocriptine or amantadine)
  • Once resolved: delay restarting antipsychotics to at least 2 weeks to reduce the risk of recurrence

Complications

  • Worsening of psychosis
  • Sepsis
  • Rhabdomyolysis
  • Acute kidney injury secondary to rhabdomyolysis
  • Permanent neurological disability

Prognosis

  • If an AKI develops, the risk of mortality is significantly increased
  • Prognosis is better if:
    • There is early recognition and management
    • There are no complications

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