Neuroleptic Malignant Syndrome

KEY FEATURES

• A catatonia-like state manifested by

  • Extrapyramidal signs

  • Blood pressure changes

  • Altered consciousness

  • Hyperpyrexia

• Uncommon but serious complication of antipsychotic treatment

• Causes include

  • Poor antipsychotic medication dosage control

    • May occur with even small doses

    • Intramuscular administration is a risk factor

  • Affective illness

  • Decreased serum iron

  • Dehydration

  • Increased sensitivity of dopamine receptor sites

• Comorbid affective disorder as well as concomitant lithium use may increase risk

• In most cases, occurs within 2 weeks of starting antipsychotic agent

CLINICAL FINDINGS

• Muscle rigidity, involuntary movements, confusion, dysarthria, dysphagia

• Pallor, cardiovascular instability, fever, pulmonary congestion, diaphoresis

• Can result in stupor, coma, death

• Differential diagnosis

  • Malignant catatonia

  • Malignant hyperthermia

  • Neurotoxic syndromes (including AIDS)

  • Various other conditions such as viral encephalitis, Wilson disease, central anticholinergic syndrome, and hypertonic states (eg, tetany, strychnine poisoning)

DIAGNOSIS

• Elevated creatine kinase and leukocytosis with left shift (increase in neutrophil-precursor band cells) in 50% of cases

TREATMENT

• Control of fever and support with fluids

• Bromocriptine, 2.5–10.0 mg orally three times daily, and amantadine, 100–200 mg orally twice daily, have been useful

• Dantrolene, 50 mg intravenously as needed to maximum of 10 mg/kg/d, can alleviate rigidity

• Efficacy of these three agents as well as the use of calcium channel blockers and benzodiazepines remains controversial

• Electroconvulsive therapy has been used in resistant cases

• Clozapine has been used safely in patients with a history of neuroleptic malignant syndrome