Surreal illustration of a brain intertwined with medication bottles, symbolizing the complexities of Neuroleptic Malignant Syndrome.

Neuroleptic Malignant Syndrome: Recognizing Atypical Presentations

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Kai Mendoza in Health & Wellness December 2025 • 4 min read.

"Early detection is key. Learn how to spot the subtle signs of NMS and ensure timely intervention for better patient outcomes."


Neuroleptic Malignant Syndrome (NMS) is a rare but serious neurological emergency, typically triggered by dopamine antagonists or withdrawal from dopamine agonists. While the classic symptoms include fever, rigidity, altered mental status, and autonomic dysfunction, NMS can sometimes present atypically, making diagnosis challenging.

This article explores a case of suspected atypical NMS following a rapid medication change. It emphasizes the importance of recognizing subtle signs and initiating prompt treatment, even when the presentation doesn't fully align with standard diagnostic criteria. Understanding the nuances of NMS presentation can improve patient outcomes and reduce the risk of severe complications.

This exploration of atypical NMS presentations aims to provide a clear understanding of diagnostic criteria, treatment approaches, and potential challenges. Recognizing and responding to these subtle variations can significantly improve patient care.

Decoding Atypical NMS: A Case Study

Surreal illustration of a brain intertwined with medication bottles, symbolizing the complexities of Neuroleptic Malignant Syndrome.

A 40-year-old woman with a history of schizophrenia presented to the emergency department exhibiting weakness, stiffness, confusion, and unresponsiveness. Her recent psychiatric admission included treatment with citalopram and risperidone, followed by a switch from intramuscular ziprasidone to oral risperidone. This rapid change, without proper titration, raised concerns.

Upon examination, the patient displayed muscular rigidity and autonomic instability (hypertension and tachycardia), but without the classic symptom of high fever. Initial treatment with diphenhydramine and lorazepam provided little relief. The care team initiated empiric NMS treatment, discontinuing risperidone and starting dantrolene and bromocriptine.

  • Key Indicators: Monitor for changes in mental status, muscle rigidity, and autonomic function, even without fever.
  • Medication Review: Be vigilant about NMS risk when making rapid changes in antipsychotic medications.
  • Early Intervention: Promptly discontinue suspected medications and initiate supportive care if NMS is suspected.
The patient's condition gradually improved with this approach. Clinicians tapered and discontinued dantrolene and bromocriptine over eight days, transitioning the patient to oral medications. She was discharged to a rehabilitation facility and fully recovered. Two months later, she was readmitted for a non-psychiatric issue and was tolerating ziprasidone without incident. This case underscores the challenges in diagnosing atypical NMS and the importance of a high index of suspicion.

Navigating the Nuances of NMS Diagnosis and Treatment

Diagnosing NMS, particularly in its atypical form, requires careful consideration of clinical presentation, medication history, and exclusion of other potential causes. While diagnostic criteria like DSM-5, Levenson, or Nierenberg are helpful, they may not fully capture the spectrum of NMS presentations. The Delphi method, which assigns point values to different symptoms, can be particularly useful in atypical cases.

Given the potential for severe outcomes, treatment should be initiated promptly upon suspicion of NMS. This includes discontinuing the offending medication(s), providing supportive care (hydration, fever management), and considering specific treatments like dantrolene and bromocriptine. Individualized treatment plans, guided by Woodbury staging, should be based on the severity of symptoms.

Resuming antipsychotic therapy after NMS requires careful planning. Clinicians should consider using lower-potency agents, titrating slowly, and avoiding concurrent lithium use. Educating patients and caregivers about the signs and symptoms of NMS is essential for early detection and prevention of recurrence. This case serves as a reminder of the importance of vigilance, especially when managing patients with complex psychiatric conditions and medication regimens.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.9740/mhc.2017.05.137, Alternate LINK

Title: Early Detection Of An Atypical Presentation Of Neuroleptic Malignant Syndrome: A Case Report

Subject: Pharmacology (medical)

Journal: Mental Health Clinician

Publisher: College of Psychiatric and Neurologic Pharmacists (CPNP)

Authors: P. Brittany Vickery, Lindsy Meadowcraft, Stephen B. Vickery

Published: 2017-05-01

Everything You Need To Know

1

What is Neuroleptic Malignant Syndrome (NMS)?

Neuroleptic Malignant Syndrome (NMS) is a severe neurological emergency. It is often triggered by the use of dopamine antagonists or the withdrawal of dopamine agonists. In this particular case, a rapid medication change, specifically a switch from intramuscular ziprasidone to oral risperidone, raised concerns. The article highlights the importance of recognizing subtle signs and initiating prompt treatment, even when the presentation doesn't fully align with standard diagnostic criteria. This involves understanding the diagnostic criteria, treatment approaches, and potential challenges related to it.

2

What are the primary symptoms of NMS to look out for?

The key indicators to monitor for NMS include changes in mental status, muscle rigidity, and autonomic function, even without the presence of a fever. In the case described, the patient displayed muscular rigidity and autonomic instability, specifically hypertension and tachycardia. It's important to remember that classic symptoms may not always be present, so a high index of suspicion is crucial for diagnosis.

3

Why is medication review important concerning NMS?

Rapid changes in antipsychotic medications can increase the risk of NMS. The article emphasizes the need to be vigilant about this risk when making such changes. In the presented case, a switch from intramuscular ziprasidone to oral risperidone without proper titration was a concern. The key takeaway is to proceed cautiously and be aware of the potential for NMS when adjusting medications.

4

What actions should be taken if NMS is suspected?

Promptly discontinuing suspected medications and initiating supportive care are crucial steps in managing NMS. In the described scenario, the care team discontinued risperidone and started treatment with dantrolene and bromocriptine. Early intervention can significantly improve patient outcomes and reduce the risk of severe complications. It's essential to have a high index of suspicion for NMS, even in atypical presentations, to ensure timely treatment.

5

How is NMS diagnosed, particularly in atypical presentations?

Diagnosing NMS, especially in its atypical form, necessitates a comprehensive approach. This includes carefully considering the clinical presentation, thoroughly reviewing the patient's medication history, and ruling out other potential causes. While diagnostic criteria such as DSM-5, Levenson, or Nierenberg are helpful, they may not fully capture the spectrum of NMS presentations. The Delphi method, which assigns point values to different symptoms, can be particularly useful in atypical cases to assist in the diagnosis process.

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