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Neuroleptic Malignant Syndrome Overview

Sep 4, 2025

Overview

This lecture covers neuroleptic malignant syndrome (NMS), its causes, clinical features, risk factors, diagnostic criteria, investigations, differential diagnoses, management, and complications.

Definition and Causes

  • Neuroleptic malignant syndrome (NMS) is a life-threatening condition caused by dopamine receptor antagonists, commonly antipsychotics.
  • Neuroleptics are drugs used to treat psychotic conditions and include typical (first generation) and atypical (second generation) antipsychotics.
  • Other drugs with dopamine antagonism (e.g., metoclopramide, tricyclic antidepressants, lithium) can also cause NMS.
  • Rapid withdrawal of dopaminergic medications (like those used in Parkinson’s disease) can trigger NMS.

Pathophysiology

  • NMS is linked to sudden reduction in central nervous system dopaminergic activity.
  • Other neurotransmitters and loss of sympathetic inhibition contribute, causing autonomic instability.
  • Increased calcium release in muscles leads to rigidity and hyperthermia.

Clinical Features

  • Symptoms typically develop over several days and can be remembered by the FEVER mnemonic:
    • F: Fever (>38°C)
    • E: Encephalopathy (altered mental state, disorientation, delirium)
    • V: Vital sign instability (tachycardia, labile blood pressure, sweating, urinary incontinence)
    • E: Enzyme elevation (increased creatine phosphokinase from rhabdomyolysis)
    • R: Rigidity (generalized lead pipe muscle rigidity)

Risk Factors

  • Initiation or dose change of neuroleptics, especially long-acting injections.
  • Higher risk in males and patients with dementia.
  • More common in young adults due to greater exposure to antipsychotics.
  • Withdrawal-induced NMS more common in older adults.
  • Possible genetic predisposition affecting D2 receptors.

Diagnosis

  • DSM-5: Requires dopamine blocker exposure, severe rigidity, and fever; plus at least two minor criteria (leukocytosis, elevated creatine kinase, dysphagia, altered consciousness, mutism, incontinence, tremor, tachycardia, sweating, labile BP).
  • Investigations: Blood tests (renal function, electrolytes, CK), blood gases (for acidosis), urinalysis (myoglobin), imaging or lumbar puncture to rule out other causes.

Differential Diagnosis

  • Meningitis, encephalitis, CNS abscess
  • Malignant hyperthermia
  • Drug toxicity (cocaine, amphetamines)
  • Serotonin syndrome

Management

  • Immediate discontinuation of the causative agent; restart dopaminergic drugs if withdrawal-induced.
  • Supportive care: IV fluids, aggressive hydration for rhabdomyolysis, correction of electrolytes.
  • Cooling methods, antipyretics, and invasive measures for severe hyperthermia.
  • Benzodiazepines for agitation; dopamine agonists (bromocriptine) and dantrolene may be used for severe cases.
  • Electroconvulsive therapy in refractory cases.

Complications

  • Respiratory failure from chest wall rigidity, requiring mechanical ventilation.
  • Cardiac arrhythmias, renal failure, DIC, DVT, and pulmonary embolism.

Key Terms & Definitions

  • Neuroleptic — Drug class used to treat psychotic disorders.
  • Dopamine antagonist — Medication that blocks dopamine receptors.
  • Rhabdomyolysis — Muscle breakdown releasing creatine kinase and myoglobin into the blood.
  • Autonomic instability — Fluctuating vital signs and autonomic symptoms.
  • Lead pipe rigidity — Uniform muscle stiffness throughout the range of movement.

Action Items / Next Steps

  • Review DSM-5 diagnostic criteria for NMS.
  • Read about serotonin syndrome and how to differentiate it from NMS.
  • Prepare for a quiz on NMS features and management.

Full transcript