Neuroleptic malignant syndrome (NMS) is a rare neurological condition associated with the use of antipsychotic medications. Autonomic dysfunction, or damage to the nerves that control involuntary bodily functions, is a key feature of the condition.

Autonomic dysfunction affects the functioning of the heart, lungs, gastrointestinal system, and bladder. People with NMS will also develop muscle rigidity, fever, and an altered mental status.

The condition can lead to life threatening complications in people who do not receive treatment quickly enough, but most who receive immediate treatment recover.

In this article, we look at the symptoms of NMS, along with its causes, treatment options, and risk factors.

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NMS is a rare and potentially deadly reaction to the use of antipsychotic medications. These medications, also called neuroleptics, prevent the overactivity of dopamine. Dopamine is a neurotransmitter that carries messages between cells.

Doctors typically prescribe antipsychotic medications to individuals with schizophrenia, bipolar disorder, and similar neurological or mental health conditions.

NMS affects approximately 0.01% to 3.2% of people who take antipsychotic medication. The condition is fatal in fewer than 10% of cases.

People typically develop symptoms of NMS within 1–3 days of exposure to an antipsychotic drug. The four main symptoms are:

  • muscle rigidity
  • fever
  • autonomic dysfunction
  • altered mental status

Altered mental status can range from mild drowsiness, irritability, and confusion to severe delirium and coma.

According to the Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5), a person must have all three of the following for a doctor to diagnose NMS:

  • exposure to a dopamine-blocking medication
  • extreme muscle rigidity
  • fever

The DSM-5 states that they should also exhibit a minimum of two of the following:

A doctor may take a blood test and urine sample to check for altered levels of white blood cells, CPK, blood pH, electrolytes, and liver enzymes.

A normal white blood cell count is 4,000–11,000 per microliter of blood. A person with NMS commonly has up to 40,000 white blood cells per microliter. People with NMS also often show elevated levels of CPK, which indicates higher disease severity.

NMS is a rare condition that can occur as a result of exposure to antipsychotic drugs. Doctors use these drugs, which decrease dopamine activity, to treat various neurological disorders.

Many medications can cause NMS, but first-generation antipsychotics are more commonly associated with the condition. These include haloperidol decanoate and fluphenazine.

Abruptly stopping medication that increases dopamine activity, such as the medications for Parkinson’s disease, can also cause NMS.

While NMS treatment is highly individualized and differs in each case, a doctor will first try to stabilize the person by correcting their blood pressure, heart rate, electrolyte levels, and blood pH. They will also ensure that the individual is properly hydrated.

People with NMS are at a greater risk of abnormal heart rates due to autonomic dysfunction and may need treatment in the form of mechanical ventilation. Doctors may also give people skeletal relaxers to prevent or stop dangerous muscle rigidity.

In some rare situations, doctors may also prescribe electroconvulsive therapy (ECT). In these cases, the doctor will admit a small electric current to the brain when the person is asleep. ECT may help alleviate symptoms in people who have not responded to other treatments.

Malignant hyperthermia (MH) is a potentially fatal condition that is similar to NMS. MH is a severe reaction to an inhalation anesthetic or muscle relaxer. It occurs due to a rare genetic mutation that a person inherits from one or both parents.

MH affects approximately 1 in 100,000 adults and 1 in 30,000 children who receive an anesthetic or a muscle relaxer. The mortality rate in people with MH is 3–5%.


NMS and MH produce similar symptoms, including fever, muscle rigidity, and an elevated heart rate.

NMS also has similarities to an acute dystonic reaction, a side effect of antipsychotic medications that causes severe muscle spasms. However, an acute dystonic reaction will not cause autonomic dysfunction, fevers, or mental status changes.


The main difference between NMS and MH is the cause of symptoms. NMS is a reaction to antipsychotic medication, whereas MH is a reaction to an anesthetic or muscle relaxer that occurs due to a genetic abnormality.

The main risk factor for developing NMS is taking antipsychotic medication. While some more potent drugs may increase a person’s risk, all antipsychotic medications can cause this condition. Taking more than one antipsychotic drug can also increase a person’s risk of developing NMS.

Other risk factors include:

Men are also twice as likely to develop this syndrome as women.

With treatment, most individuals with NMS will recover within 2–14 days. Once a person has recovered, a doctor might prescribe them a different antipsychotic medication or a lower dosage.

If a person does not receive treatment for NMS quickly enough, they can develop serious complications. These include pulmonary aspiration, where a person inhales a fluid or object into their windpipe and lungs. They may also develop kidney failure or multiple organ failure.

While NMS can be life threatening, fewer than 10% of cases are fatal.

NMS is a rare reaction to antipsychotic medications. The symptoms include an altered mental status, muscle rigidity, autonomic dysfunction, and fever.

Although some people with NMS can develop fatal complications, most people recover after a few days of receiving the correct treatment.