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The condition is characterized by rigidity, altered mental status, hyperthermia, and autonomic dysfunction (i.e., diaphoresis, tachycardia, tachypnea, and labile blood pressure). 1 It occurs in about 0.02% to 0.03% of patients receiving antipsychotic medications, with a mortality rate of up to 5.6% according to recent estimates. 2 It can also be caused by dopamine antagonist antiemetics (eg, metoclopramide). 23
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The creatine kinase level is usually greater than 1000 IU/L. 1, 3 Brain imaging, lumbar puncture, metabolic testing, and drug immunoassays may be considered to exclude alternative causes (eg, toxic, metabolic, infectious, structural). 1, 2 A complete medical history helps distinguish Neuroleptic Malignant Syndrome (NMS) from sympathomimetic or anticholinergic toxicity and serotonin syndrome. 2, 4
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Risk factors include use of high-potency first-generation antipsychotic agents (i.e., haloperidol, fluphenazine), high doses, rapid dose escalation, parenteral formulations, and history of NMS. Patients receiving stable doses may develop NMS during acute illness. 2 – 5
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Patients may require an intensive care setting to provide volume resuscitation, treat hyperthermia, and manage end-organ dysfunction. 3, 5
Benzodiazepines (ie, intramuscular or intravenous lorazepam 1 to 2 mg every 4 to 6 hours) are first-line treatments for muscle rigidity and sympathetic overactivity, including agitation and hyperthermia. 3, 5 Cooling blankets and ice packs should also be used for hyperthermia.
The effectiveness of dantrolene, dopamine agonists such as bromocriptine, and electroconvulsive therapy is not well established. These may be considered if symptoms worsen despite initial treatment, with guidance on pharmacotherapy dosages provided by the local poison center.
Venous thromboprophylaxis should be considered in all patients. 4
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When recognized and treated early, most patients make a full recovery. 5
If continued use of antipsychotic medications is warranted, measures to decrease the risk of recurrence (estimated between 10% and 30%) include restarting at least 2 weeks after resolution of symptoms (4 weeks for depot injections), the use of antipsychotic agents of low potency, low doses and slow dose escalation. 2 – 5
Summary • NMS is a rare condition that represents an adverse effect of treatment, generally with antipsychotic drugs. • It is more likely with the use of antipsychotics in high doses or rapidly titrated. If NMS is suspected, pharmacological treatment should be discontinued. This can relieve symptoms and prevent complications. • Re-exposure to antipsychotics will be necessary in many patients with NMS. It is recommended to start it once the symptoms of NMS have resolved, and after a minimum pharmacological clearance period of 5 to 14 days, according to the needs, risks and potential benefits of each case. • Antipsychotic treatment should be restarted with low-potency drugs, in low doses, and through slow titration. • In addition, periodic clinical evaluation is necessary in order to detect any symptoms of NMS. Additional studies will provide more information about NMS. |
Bibliographic references
- Gurrera RJ, Caroff SN, Cohen A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry 2011; 72 :1222–8. CrossRef PubMed Google Scholar
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