A Guide to Neuroleptic Malignant Syndrome

Medically Reviewed By Alyssa Peckham, PharmD, BCPP
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Neuroleptic malignant syndrome is a severe reaction to some medications. Characteristic signs include fever, stiff muscles, rapid heart rate, and altered mental condition. Although extremely uncommon, it can be life threatening and requires immediate treatment. If you believe you or someone you know is experiencing this, you should seek immediate medical care.

This article will explain what neuroleptic malignant syndrome (NMS) is. It will also describe symptoms, causes, and treatment options for the condition.

What is neuroleptic malignant syndrome?

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Alexey Kuzma/Stocksy United

NMS is a life threatening reaction to

neuroleptic medications, which are also called antipsychotic medications. Because of improved awareness, earlier diagnosis, and better treatments, the mortality rate of this condition is decreasing.

In most cases, the syndrome occurs after a dramatic increase in the dose of the medication. In some cases, stopping or switching medications quickly can also cause NMS.

Genetics could be a risk factor, although research into this subject is still ongoing.

What are the signs and symptoms?

Symptoms of NMS typically begin within hours of starting treatment with neuroleptic medications but can emerge for up to 2 weeks after.

The four classic symptoms include:

  • changing mental status, such as agitation, confusion, drowsiness, and unresponsiveness
  • stiffening muscles
  • experiencing a fever of greater than 100.4ºF (38ºC)
  • changing vital signs, such as:
    • increased heart rate
    • abnormal heartbeats
    • fast breathing
    • dramatic changes in blood pressure

When to contact a doctor

NMS is a life threatening disorder that requires treatment as early as possible. Those who have begun treatment with neuroleptic drugs should be monitored closely for any signs and symptoms.

If any symptoms are present, seek immediate medical care.

Other disorders with similar symptoms

Some disorders have similar symptoms to NMS, including:

  • Heatstroke: Symptoms of this condition include fever and altered mental status, but these symptoms usually have a much faster onset than with NMS. During a heatstroke, the muscles are limp rather than stiff.
  • Central nervous system infections: These infections present as fever and changes in mental status, however, the stiffness in the muscles tends to be from seizures rather than NMS. Typically, a prior illness causes the infection.
  • Serotonin syndrome: Symptoms of this sydrome include altered mental status, rapid heart rate, changes in blood pressure, fast breathing, and stiff muscles. Lab tests and the presence of nausea or vomiting help to distinguish it from NMS.

What causes it?

Neuroleptic medications, also called antipsychotic medications, can trigger NMS. However, this occurs very rarely. Only 0.02–3% of people who take these medications develop NMS.

Doctors use neuroleptic drugs to manage symptoms and treat many psychiatric disorders. These medications work by blocking dopamine receptors o

r partially regulating them.

Dopamine is a chemical in your nervous system that transfers messages between cells, and research suggests that manipulating it in certain areas of the brain can trigger NMS.

First generation neuroleptics

Neuroleptic drugs fall into two classes: “typical” or first generation neuroleptics, and “atypical” or second generation neuroleptics.

First generation neuroleptics, developed in the 1950s, are

FDA approved to treat and manage various conditions.

Conditions that first generation

neuroleptics can treat include acute mania, agitation, bipolar disorder, Tourette’s syndrome, and hyperactivity.

Some first generation

neuroleptics include:

  • chlorpromazine (Thorazine)
  • fluphenazine (Prolixin)
  • haloperidol (Haldol)
  • loxapine (Loxitane)
  • perphenazine (Trilafon)
  • thioridazine (Mellaril)

Second generation neuroleptics

Because of common complications with first generation neuroleptic medications, researchers have more recently developed a second generation.

Initially developed in the 1980s with ongoing development today, these medications are FDA approved to treat and manage various conditions. Conditions that these medications can treat include psychosis, treatment-resistant schizophrenia, bipolar disorder, schizoaffective disorder, and agitation.

Second generation

neuroleptics include:

  • aripiprazole (Abilify)
  • asenapine (Saphris)
  • brexpiprazole (Rexulti)
  • cariprazine (Vraylar)
  • clozapine (Clozaril)
  • iloperidone (Fanapt)
  • olanzapine (Zyprexa)
  • paliperidone (Invega)
  • quetiapine (Seroquel)
  • risperidone (Risperdal)
  • ziprasidone (Geodon)
Learn more about

neuroleptic medications here.

Dopaminergic medications

Occasionally, NMS happens when dopaminergic medications are suddenly stopped or switched. These medications are most often used to treat Parkinson’s disease, and can include:

  • levodopa
  • amantadine
  • tolcapone

Further medications that can trigger neuroleptic malignant syndrome

Other medications, such as lithium and certain antinausea medications, have also triggered NMS. Antinausea medications that can trigger NMS include metoclopramide and promethazine.

How is it diagnosed?

Usually, doctors will diagnose this condition based on the presence of symptoms, including:

  • stiff muscles
  • fever greater than 100.4ºF (38ºC)
  • change in mental status
  • rapid heartbeat
  • changes in blood pressure
  • excessive sweating
  • excessive saliva
  • a history of taking a neurleptic medication in the past 4 weeks

How is it treated?

NMS is considered a neurologic emergency and treatment must begin immediately. If taking a neuroleptic medication caused NMS, that medication must be stopped at once.

If the cause is from the withdrawal of dopaminergic medication, then a healthcare professional should administer this medication right away.

Medications

When recognized early and treated quickly, NMS is rarely fatal. Recovery is around 2–14 days.

Your doctor may administer the following medications during treatment:

  • benzodiazepines to control agitation, administered through your veins as an IV injection
  • dantrolene to relax muscles and potentially decrease fever
  • bromocriptine and amantadine to help restore dopamine activity in the body

Summary

NMS is a neurological condition that may occur after starting or changing the dose of neuroleptic medication. If left untreated, NMS can be fatal.

The symptoms of fever, stiff muscles, rapid heart rate, and altered mental status can start within hours of taking the medication. These symptoms can also progress slowly, over a few days or weeks.  

Doctors diagnose this condition by examining your symptoms and your medical history, including any recent changes in medication.

Treatment can include discontinuing the medication and managing symptoms, such as reducing fever and providing IV fluid hydration.

With fast recognition and treatment, NMS does not have to be fatal. As awareness increases, the mortality rate decreases.

If you or someone you know is experiencing symptoms of NMS, seek medical advice immediately.

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Medical Reviewer: Alyssa Peckham, PharmD, BCPP
Last Review Date: 2022 Mar 22
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THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.
  1. Ameer, M. A., et al. (2021). Neuroleptic medications. https://www.ncbi.nlm.nih.gov/books/NBK459150/
  2. Simon, L. V., et al. (2022). Neuroleptic malignant syndrome. https://www.ncbi.nlm.nih.gov/books/NBK482282/
  3. Tanen, D. (2021). Neuroleptic malignant syndrome. https://www.merckmanuals.com/professional/injuries-poisoning/heat-illness/neuroleptic-malignant-syndrome#