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Neuroleptic Malignant Syndrome

By

David Tanen

, MD, David Geffen School of Medicine at UCLA

Last full review/revision Jul 2019| Content last modified Jul 2019

Neuroleptic malignant syndrome is confusion or unresponsiveness, muscle rigidity, high body temperature, and other symptoms that occur when certain antipsychotic (neuroleptic) drugs or anti-vomiting (antiemetic) drugs are used.

  • Neuroleptic malignant syndrome develops in a very small number of people who are given certain types of drugs.
  • Symptoms include a dangerously high body temperature, muscle rigidity, and agitation.
  • Doctors base the diagnosis on the person's symptoms and on what they find during a physical examination.
  • Treatment involves stopping the drug, reducing body temperature, and providing support in an intensive care unit.

(See also Overview of Heat Disorders.)

Neuroleptic malignant syndrome develops in a small number of people who are treated with antipsychotic or antiemetic drugs (see table Drugs That Can Cause Neuroleptic Malignant Syndrome), usually within the first few weeks of treatment. The risk of developing the syndrome varies between 0.02% and 3% depending on many factors. The syndrome is most common among men who, because they are agitated, are given rapidly increased doses of antipsychotics or high doses initially. Doctors are not sure why the syndrome develops.

Drugs That Can Cause Neuroleptic Malignant Syndrome

Class

Drugs

Antipsychotics, traditional

Chlorpromazine

Fluphenazine

Haloperidol

Loxapine

Mesoridazine

Molindone

Perphenazine

Pimozide

Thioridazine

Thiothixene

Trifluoperazine

Antipsychotics, newer

Aripiprazole

Clozapine

Olanzapine

Paliperidone

Quetiapine

Risperidone

Ziprasidone

Antiemetics (anti-vomiting drugs)

Domperidone

Droperidol

Metoclopramide

Prochlorperazine

Promethazine

Symptoms

Symptoms usually develop over a few days and include

  • Confusion, agitation, or coma
  • Muscle rigidity
  • A high temperature, often over 104° F (40° C)
  • A fast heart rate
  • A fast breathing rate
  • High or variable (labile) blood pressure

Damaged muscles release the protein myoglobin, which is excreted in the urine and turns the urine brown. This condition (myoglobinuria) can cause acute kidney injury or even kidney failure. About 10 to 20% of people die, even with rapid treatment.

Diagnosis

  • Typical symptoms developing in a person who is taking a drug known to cause neuroleptic malignant syndrome

Doctors suspect the diagnosis when people taking a drug known to cause neuroleptic malignant syndrome develop characteristic symptoms and physical examination findings, particularly severe muscle rigidity. There are no tests that confirm the diagnosis. However, because other disorders (for example, meningitis and sepsis) can cause similar symptoms, doctors often do tests for those disorders. Doctors also do blood and urine tests to look for muscle protein breakdown and kidney injury.

Treatment

  • Stopping the drug
  • Controlling the fever
  • Providing intensive supportive care

People with this syndrome are usually treated in an intensive care unit. The drug is stopped and fever is controlled, usually by wetting (misting) and blowing air over the skin or by using special cooling blankets. People who are very agitated are given sedatives by vein. Other treatments of possible but unproven benefit are often used because of the severity of this condition. These include dantrolene (a muscle relaxant, to reduce fever and muscle damage) and bromocriptine (to improve nerve function).

Drugs Mentioned In This Article

Generic Name Select Brand Names
Prochlorperazine COMPRO
Chlorpromazine No US brand name
Metoclopramide REGLAN
bromocriptine PARLODEL
Paliperidone INVEGA
Fluphenazine No US brand names
Aripiprazole ABILIFY
Promethazine PROMETHEGAN
Haloperidol HALDOL
Thiothixene NAVANE
Ziprasidone GEODON
Risperidone RISPERDAL
dantrolene DANTRIUM
Droperidol INAPSINE
Quetiapine SEROQUEL
Olanzapine ZYPREXA
Clozapine CLOZARIL
Pimozide ORAP
Loxapine ADASUVE

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