What is Neuroleptic Malignant Syndrome (NMS)?

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Last updated: May 27, 2025View editorial policy

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From the Guidelines

Neuroleptic malignant syndrome (NMS) is a life-threatening condition that requires immediate discontinuation of the causative antipsychotic medication and supportive care, including cooling measures, IV fluids, and monitoring in an intensive care setting. The incidence of NMS has been difficult to determine, with estimates ranging from 0.02% to 3% 1. Fortunately, mortality from NMS has decreased from 76% in the 1960s to <10% to 15% more recently 1.

Key Features and Management

NMS presents with four cardinal features: hyperthermia, muscle rigidity, altered mental status, and autonomic instability. Management involves primarily supportive care and removal of the initiating agent 1. Specific pharmacological treatments may include benzodiazepines for agitation, and external cooling measures such as cooling blankets for fever 1.

Risk Factors and Prevention

Coadministration of psychotropic agents seems to be an especially high risk factor for precipitating NMS; in one study, more than half of people with reported NMS cases were taking concomitant psychotropic agents 1. Other risk factors include dehydration, physical exhaustion, preexisting organic brain disease, and the use of long-acting depot antipsychotics 1.

Treatment and Recovery

Recovery usually takes 7-10 days after medication discontinuation, but complications can include rhabdomyolysis, acute kidney injury, and respiratory failure. After recovery, if antipsychotic treatment is necessary, a different class with lower potency should be introduced gradually after at least two weeks, with close monitoring for recurrence. Immediate recognition and treatment of NMS are crucial to reduce morbidity and mortality.

From the Research

Definition and Characteristics of Neuroleptic Malignant Syndrome

  • Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction 2.
  • It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission 2.
  • The diagnosis of NMS often presents a challenge because several medical conditions generate similar symptoms, including mental status changes, muscle rigidity, hyperthermia, and autonomic dysfunction 3.

Treatment and Management of Neuroleptic Malignant Syndrome

  • Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases 2.
  • Dantrolene, bromocriptine, and electroconvulsive therapy (ECT) have been reported as potential treatments for NMS, with dantrolene leading to off-label use for NMS 4, 5, 6.
  • A subgroup analysis regarding NMS severity showed that the mortality under specific NMS pharmacotherapy (dantrolene, bromocriptine) and under ECT was significantly lower than under purely symptomatic therapy in severe NMS 4.
  • Collaboration between psychiatry and other medical specialities may be the key to a successful outcome in the management of NMS 3.

Prevention and Risk Reduction of Neuroleptic Malignant Syndrome

  • Reducing the risk factors, early recognition of suspected cases, and prompt management can significantly reduce morbidity and mortality of this dangerous condition 3.
  • Maintaining vigilant awareness of the clinical features of NMS to diagnose and treat the disorder early remains the most important strategy by which physicians can keep mortality rates low and improve patient outcomes 2.
  • It is essential to recognize that NMS can be underdiagnosed because it is poorly understood and often unrecognized, affecting all age groups with a significant mortality rate 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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