Updated: 12/27/2021

Neuroleptic Malignant Syndrome

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  • Snapshot
    • A 32-year-old woman is brought to the psychiatric emergency department by emergency medical service for a suicidal attempt. The patient expressed to the hospital staff that she wishes to end her life due to concerns someone is attempting to kidnap her. She has a medical history of schizophrenia and has not been adherent to her aripiprazole. The patient attempted to attack 1 of the security guards due to the belief that he is involved in her kidnapping. She was given multiple doses of intramuscular haloperidol. Approximately 2 days later, the patient's temperature is 102°F (38.9°C), blood pressure is 163/95 mmHg, pulse is 115/min, and respirations are 26/min. On physical examination, the patient is diffusely rigid and is profusely diaphoretic.
  • Introduction
    • Overview
      • life-threatening neurologic and psychiatric emergency associated with neuroleptic (antipsychotic) medication use
      • classic clinical syndrome tetrad
        • altered mental status
        • fever
        • rigidity
        • autonomic instability
  • Epidemiology
    • Demographics
      • typically seen in young adults
        • can occur at any age
    • Risk factors
      • antipsychotic use
        • first- and second-generation
      • antiemetic use
        • e.g., metoclopramide and prochlorperazine
      • antiparkinson medication withdrawal
        • also called neuroleptic malignant-like syndrome or parkinsonism hyperpyrexia syndrome
  • ETIOLOGY
    • Pathophysiology
      • unknown but dopamine receptor blockade in the central nervous system is believed to be involved
    • Associated conditions
      • psychiatric disorders that require high or frequent doses of antipsychotic medications
  • Presentation
    • History
      • tetrad usually occurs over the course of 1-3 days after neuroleptic use
    • Physical exam
      • altered mental status
        • agitated delirium
        • confusion
        • catatonia
        • mutism
      • fever
        • ≥ 38°C
      • rigidity
        • typically diffuse
        • can be described as a "lead-pipe rigidity"
        • patients may also have a tremor (45-92% of cases)
      • autonomic instability
        • tachycardia
          • patients may develop dysrhythmias
        • hypertension or labile blood pressure
        • tachypnea
        • diaphoresis
      • hyporeflexia
  • Studies
    • Labs
      • ↑ creatine kinase
        • usually > 1000 U/L
      • basic metabolic panel
        • hypo- or hypernatremia
        • hyperkalemia
        • hypomagnesemia
        • hypocalcemia
        • metabolic acidosis
        • acute renal failure
          • may occure if myoglobinuria
      • ↓ iron concentration
        • sensitive but not specific
  • Differential
    • Serotonin syndrome
      • key distinguishing factors
        • acute onset
        • myoclonus
        • hyperreflexia
        • mydriasis (large pupils)
    • Malignant hyperthermia
      • key distinguishing factorss
        • offending agents are
          • halogenated inhalational anesthetics
          • succinylcholine
  • Treatment
    • Prevention
      • Conservative use of antipsychotics
      • Gradual titration of antopsychotics
    • Lifestyle
      • supportive care
        • indication
          • first-line in preventing further complications
            • intravenous fluids to prevent dehydration and acute kidney injury from myglobinuria
            • electrolyte repletion to prevent cardiac arrythmias and seizures
    • Pharmacologic
      • discontinue the offending agent
        • indication
          • first-line to prevent further progression of neuroleptic malignant syndrome
      • benzodiazepines
        • indication
          • usually initially used along with dantrolene in moderate or severe cases
        • medication
          • lorazepam
          • diazepam
      • dantrolene 
        • indication
          • usually given with benzodiazepines in moderate or severe cases
            • effective in relaxing skeletal muscles
      • bromocriptine
        • indication
          • administered after benzodiazepines and dantrolene is administered in order to restore dopaminergic tone
        • alternative agent
          • amantadine
  • Complications
    • Seizure
    • Cardiac dysrhythmia
    • Myocardial infarction
    • Respiratory failure
    • Hepatic failure
    • Acute renal failure
    • Deep venous thrombosis
    • Disseminated intravascular coagulation
  • Prognosis
    • Natural history of disease
      • most cases resolve within 2 weeks
    • Survival with treatment
      • improved

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