Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a rare and life-threatening reaction to the use of almost any kind of neuroleptic (antipsychotic) medication. It causes a high fever and muscle stiffness. Call 911 or go to the nearest hospital if you’re experiencing symptoms of NMS.


What is neuroleptic malignant syndrome?

Neuroleptic malignant syndrome (NMS) is a rare and life-threatening reaction to the use of any neuroleptic medication. Neuroleptics, also known as antipsychotic medications, treat and manage symptoms of many psychiatric conditions.

NMS is characterized by the following:

  • High fever (hyperthermia).
  • Stiff, rigid muscles that can lead to eventual muscle breakdown.
  • Altered mental status.
  • Autonomic nervous system dysfunction (dysautonomia).

Your autonomic nervous system regulates certain body processes, such as blood pressure and your rate of breathing. Autonomic dysfunction leads to wide swings in blood pressure, excessive sweating (secondary hyperhidrosis) and excessive secretion of saliva (spit).

NMS is potentially life-threatening and requires immediate medical attention in a hospital setting.


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What are neuroleptic medications?

Neuroleptics, also known as antipsychotic medications, fall into two classes: first-generation or “typical” antipsychotics and second-generation or “atypical” antipsychotics.

Healthcare providers prescribe first- and second-generation antipsychotics for various neuropsychiatric conditions, including:

Which drugs cause neuroleptic malignant syndrome?

The following medications are associated with NMS:

Typical neuroleptic (antipsychotic) medications:

Atypical neuroleptic (antipsychotic) medications:

Antiemetic medications:

Dopaminergic (antiparkinson) medications (from withdrawal):


What is the difference between neuroleptic malignant syndrome and malignant hyperthermia?

Malignant hyperthermia is a rare and severe reaction to general anesthesia drugs and muscle relaxants.

Common symptoms include muscle rigidity, slow/decreased reflexes (hyporeflexia) and changes in skin, including bluish discoloration or flushing.

These symptoms may look similar to NMS. However, in most cases, healthcare providers can tell the two conditions apart based on the medical history of the affected person — whether they recently had exposure to an anesthetic or a neuroleptic medication.

What is the difference between neuroleptic malignant syndrome and serotonin syndrome?

Serotonin syndrome is caused by serotonergic agents such as antidepressants, amphetamines, antihistamines and mood stabilizers. Serotonin syndrome happens when there’s too much serotonin in your body.

Symptoms of serotonin syndrome include muscle rigidity, increased/faster reflexes (hyperreflexia), diarrhea, sweating, muscle jerks (myoclonus) and altered mental state. High fever (hyperthermia) and muscle rigidity are usually less severe with serotonin syndrome than with NMS.

Your healthcare provider can distinguish between serotonin syndrome and NMS by both your history and your symptoms.


Who does neuroleptic malignant syndrome affect?

Neuroleptic malignant syndrome (NMS) can affect anyone taking neuroleptic (antipsychotic) medications.

Although two-thirds of NMS cases are thought to occur within the first week of starting neuroleptic medications, the syndrome may happen at any time during treatment.

How common is neuroleptic malignant syndrome?

Neuroleptic malignant syndrome (NMS) is rare. Approximately 0.01% to 3.2% of people taking neuroleptic (antipsychotic) medications develop NMS.

Cases have been decreasing due to newer medications that are less likely to cause NMS and increased awareness of the syndrome.

Symptoms and Causes

What are the symptoms of neuroleptic malignant syndrome?

Symptoms of neuroleptic malignant syndrome typically develop over one to three days and include:

If you’re experiencing these symptoms, it’s important to call 911 and get medical treatment as soon as possible.

How do neuroleptics cause NMS?

Neuroleptic malignant syndrome (NMS) can happen from a single dose, increasing dose or the same dose of neuroleptic (antipsychotic) medication. NMS is primarily associated with first-generation antipsychotics but can occur, to a lesser degree, with second-generation antipsychotics, antiemetics, and the withdrawal of anti-Parkinson, or dopaminergic, medication.

Scientists are still learning about the exact cause of neuroleptic malignant syndrome (NMS), but it’s currently hypothesized that it’s caused by dopamine D2 receptor antagonism. Dopamine is a neurotransmitter (chemical substance) that acts to convey messages from one cell to another. Neuroleptics block this messenger from entering cells at a specific receptor.

When the dopamine receptors in your hypothalamus and/or your spinal cord are blocked, it causes increased muscle stiffness. The interference with the dopamine receptors in your hypothalamus is also responsible for high fever as well as significant changes in blood pressure, as seen in NMS.

Diagnosis and Tests

How is neuroleptic malignant syndrome diagnosed?

In order for healthcare providers to diagnose NMS, you must have all of the following symptoms or conditions:

  • You’re taking a neuroleptic medication or have suddenly stopped a dopaminergic medication.
  • You have severe muscle rigidity (stiffness), which is causing muscle breakdown.
  • You have a high fever.
  • You have altered mental status.

In addition, you must have at least two of the following symptoms:

  • Excessive or abnormal sweating.
  • Difficulty swallowing.
  • Incontinence (loss of bladder or bowel control).
  • Rapid heart rate (tachycardia).
  • Sudden inability to speak.
  • Elevated or frequently fluctuating blood pressure.
  • Leukocytosis (increased white blood cell count).
  • Elevated creatine phosphokinase (CPK) due to muscle breakdown.
  • Slow or limited reflexes (hyporeflexia).

What tests will be done to diagnose neuroleptic malignant syndrome?

Your healthcare provider may order the following tests if they suspect you have neuroleptic malignant syndrome (NMS):

Management and Treatment

How is neuroleptic malignant syndrome treated?

Neuroleptic malignant syndrome (NMS) is a medical emergency, so quick diagnosis and treatment are essential. If you have NMS, you’ll need to receive care in a hospital setting — most likely an intensive care unit (ICU).

In all cases of NMS, healthcare providers discontinue the use of the neuroleptic (antipsychotic) medication that caused NMS. Treatment also involves treating the symptoms of NMS and preventing complications. Treatments could include:

  • Maintaining cardiorespiratory stability through mechanical ventilation, antiarrhythmic medications and/or pacemakers.
  • Maintaining your electrolyte balance through IV fluids.
  • Lowering your fever using cooling blankets, ice water and/or ice packs.
  • Lowering your blood pressure, if it’s elevated, through medication.
  • Treating or preventing blood clots through heparin (blot clot medication).
  • Providing medications that can reverse your low dopamine state.
  • Providing muscle or skeletal relaxants.


What are the risk factors for developing neuroleptic malignant syndrome?

Risk factors for developing neuroleptic malignant syndrome (NMS) include the initiation (starting) or increase in the dosage of neuroleptic (antipsychotic) medication. The use of more than one neuroleptic medication or lithium also increases the risk. Finally, abrupt cessation (stopping) of a dopaminergic medication (such as a Parkinson’s medication) may cause NMS.

Outlook / Prognosis

What is the prognosis (outlook) for neuroleptic malignant syndrome?

If neuroleptic malignant syndrome (NMS) is diagnosed quickly and treated aggressively and appropriately, most people recover within two to 14 days.

Delayed treatment can result in significant complications, such as muscle, kidney, heart and/or lung issues.

NMS can result in death if it’s not treated quickly enough. The mortality (death) rates for NMS range from 5% to 20%. However, the mortality rate has improved over the past few decades due to awareness of NMS and the use of new antipsychotic medications.

Many people can successfully restart neuroleptic (antipsychotic) medications under guidance from their healthcare provider.

What are the complications of neuroleptic malignant syndrome?

Unfortunately, complications of neuroleptic malignant are common and severe. While some complications result from the characteristic symptoms of NMS and autonomic dysfunction, others, especially infections, may occur from a prolonged stay in an intensive care unit (ICU).

Complications of NMS include:

Because the complications are severe and life-threatening, it’s important to call 911 and seek medical care as soon as possible if you’re experiencing symptoms of NMS. Again, NMS is a life-threatening emergency and may require ICU (intensive care unit) admission.

When should I see my healthcare provider?

If you take one or more neuroleptic (antipsychotic), antiemetic and/or dopaminergic (antiparkinson) medications, it’s important to see your healthcare provider regularly to make sure the medication is working for you. It’s also important to ask your healthcare provider about the side effects of the medications you’re taking and what symptoms to look out for.

When should I go to ER for neuroleptic malignant syndrome?

If you’re experiencing symptoms of neuroleptic malignant syndrome (NMS), such as a very high fever and stiff muscles, it’s absolutely critical to call 911 or get to the nearest hospital as soon as possible. NMS requires immediate medical treatment and can result in death if it’s not treated quickly and properly.

A note from Cleveland Clinic

Neuroleptic malignant syndrome (NMS) is a serious and life-threatening condition, so if you’re experiencing symptoms, getting medical care as soon as possible is crucial. It’s much easier to treat NMS in its early phase. Even though NMS is rare, it’s important to talk to your healthcare provider or pharmacist about side effects and symptoms to look out for if you take neuroleptic (antipsychotic) medications. They’re there to help you.

Medically Reviewed

Last reviewed by a Cleveland Clinic medical professional on 04/12/2022.

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