What is Neuroleptic Malignant Syndrome (NMS)?

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Last updated: May 5, 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 offending antipsychotic medication and intensive care monitoring with supportive care. The management of NMS involves a comprehensive approach, including discontinuation of the antipsychotic medication, intensive care monitoring, and supportive care with IV fluids, cooling measures, and electrolyte correction 1.

Key Features of NMS

  • Hyperthermia (high fever often exceeding 38°C)
  • Muscle rigidity
  • Altered mental status
  • Autonomic instability (fluctuating blood pressure, tachycardia, diaphoresis) Specific pharmacological treatments for NMS include dantrolene and bromocriptine or amantadine as dopamine agonists to counteract dopamine blockade 1.

Pathophysiology of NMS

The cause of NMS is postulated to be a lack of dopaminergic activity in the CNS, principally affecting the D2 receptors, leading to manifestations such as hyperthermia, muscle rigidity, and altered mental status 1.

Risk Factors for NMS

Risk factors for NMS include high-potency antipsychotics, rapid dose escalation, parenteral administration, dehydration, and previous NMS episodes 1.

Treatment and Prevention

Treatment typically continues for 7-10 days, with gradual tapering, and after recovery, if antipsychotic treatment is necessary, a different class with lower potency should be introduced at low doses after at least two weeks, with careful monitoring 1. Some key points to consider in the management of NMS include:

  • Immediate discontinuation of the offending antipsychotic medication
  • Intensive care monitoring with supportive care
  • Specific pharmacological treatments such as dantrolene and bromocriptine or amantadine
  • Careful monitoring and gradual tapering of treatment
  • Introduction of a different class of antipsychotic medication with lower potency after recovery, if necessary.

From the Research

Definition and Characteristics of Neuroleptic Malignant Syndrome

  • Neuroleptic malignant syndrome (NMS) is an under-recognized yet sometimes fatal complication of antipsychotic drug therapy 2
  • NMS is comprised of hyperthermia, rigidity, autonomic disturbances, and altered consciousness 2
  • It is a neurological emergency caused by dysregulation of dopaminergic neurotransmission 3

Diagnosis and Treatment

  • Diagnosis of NMS relies primarily upon medical history and symptomatology 4
  • Treatment involves cessation of dopamine-receptor antagonists and supportive measures 3
  • In more severe cases, bromocriptine, dantrolene, benzodiazepines, and/or electroconvulsive therapy should be considered 3, 5
  • Dantrolene has been reported as a potential treatment for NMS and led to off-label use for NMS 4

Therapy Regimes and Outcome

  • A systematic case series analysis found that specific NMS pharmacotherapy (dantrolene, bromocriptine) and electroconvulsive therapy (ECT) were superior to purely symptomatic therapy in severe NMS cases 5
  • However, no statistically significant differences regarding mortality rate or duration of treatment were found between dantrolene, bromocriptine, or ECT compared to supportive care in mild and moderate cases 5
  • ECT showed the lowest mortality rate in severe NMS cases 5

Critical Care and Emergency Medicine

  • NMS can become a critical illness, but there is often rapid recovery 6
  • Mortality proximate to NMS was uncommon, but late mortality remained substantial 6
  • Stricter criteria should be applied when diagnosing NMS in critical care and emergency medicine settings 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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