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For further information, see CMDT Part 25-11: Schizophrenia Spectrum Disorders

Key Features

  • A catatonia-like state manifested by

    • Extrapyramidal signs

    • Blood pressure changes

    • Altered consciousness

    • Hyperpyrexia

  • Uncommon complication of antipsychotic treatment

  • 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, 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)


  • Elevated creatine kinase and leukocytosis with left shift in 50% of cases


  • Control of fever and intravenous fluid support

  • Bromocriptine, 2.5–10.0 mg three times daily orally, and amantadine, 100–200 mg twice daily orally, can be tried

  • Dantrolene, 50 mg intravenously as needed to maximum of 10 mg/kg/day, 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

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