What are the other Names for this Condition? (Also known as/Synonyms)

• Drug-Induced Movement Disorder
• Hyperthermia
• Neuroleptic-Induced Acute Dystonia

What is Neuroleptic Malignant Syndrome? (Definition/Background Information)

• Neuroleptic Malignant Syndrome is a potentially life-threatening condition usually triggered by certain types of neurological or psychiatric medications
• Individuals with disorders of the nervous system, as well as behavioral or mood disorders, are treated with medications that occasionally have side effects
• Certain side effects are classified as Neuroleptic Malignant Syndrome when in an individual treated with these medications develop such side effects including fever, altered mental status, and bodily rigidity
• The risk factors for Neuroleptic Malignant Syndrome include switching between medications and increasing dose. With early intervention, including stoppage of the medication, complications, such as brain and muscle damage, can be avoided
• Neuroleptic Malignant Syndrome is often suspected and treated before actual confirmation, due to historical research showing that delay in treatment leads to worse outcomes

Who gets Neuroleptic Malignant Syndrome? (Age and Sex Distribution)

• Neuroleptic Malignant Syndrome is a relatively rare condition. Also, since it is not always confirmed before treatment, numbers vary
• Nearly any age group may be affected by NMS; it has been reported in individuals from less than one year of age to 78 years of age
• It seems to be most common in young adults in their early 20s
• Males have been noted to experience the condition at twice the rate of females
• All racial and ethnic groups are at risk and no specific preference is reported

What are the Risk Factors for Neuroleptic Malignant Syndrome? (Predisposing Factors)

• One can have an increased risk of Neuroleptic Malignant Syndrome from taking any of various neurologically or psychiatrically active medications, both of the older, stronger classes, as well as newer alternatives
• Risk is increased with switching between such different neuroleptic medications
• Abruptly increasing the dose of neuroleptic medication being taken increases the risk
• Having had a previous episode of NMS is thought to increase the risk, especially if a neuroleptic drug is restarted soon and/or quickly after the previous episode is resolved
• Some evidence suggests that taking lithium at the same time as restarting a neuroleptic after an episode of Neuroleptic Malignant Syndrome increases the risk for a recurrence
• A genetic predisposition is also suspected, which could explain recurrent cases even in individuals, who are not restarted on the medication

It is important to note that having a risk factor does not mean that one will get the condition.  A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors.  Some risk factors are more important than others.  

Also, not having a risk factor does not mean that an individual will not get the condition.  It is always important to discuss the effect of risk factors with your healthcare provider.  

What are the Causes of Neuroleptic Malignant Syndrome? (Etiology)

• Neurological change in autonomic neurons (that control certain automatic functions in the body) in response to external chemicals (medications) can cause Neuroleptic Malignant Syndrome
• Decreased activity of a chemical in the brain, called dopamine, is also thought to contribute, typically because neuroleptic medications block dopamine’s activity in certain nerve cells
• A genetic basis related to cellular receptors to dopamine in the brain is also suspected in many cases

What are the Signs and Symptoms of Neuroleptic Malignant Syndrome?

The signs and symptoms of Neuroleptic Malignant Syndrome include:

• Altered mental status
• High fever
• Extreme perspiration (diaphoresis)
• Elevated heart rate (tachycardia)
• Muscle rigidity (hypertonia)
• Incontinence
• Dysautonomia: Disruption of certain automatic functions in the body, such as temperature control, heart rate, and bowel and bladder, accounting for many of the above symptoms, as well as high or low blood pressure
• Seizures

An estimated two-thirds of cases occur within the first 1-2 weeks of treatment with a neuroleptic drug. However, the onset of Neuroleptic Malignant Syndrome can be at any time while taking such drug.  

How is Neuroleptic Malignant Syndrome Diagnosed?

Neuroleptic Malignant Syndrome is typically diagnosed in the following manner:

• Medical history, measurement of an individual’s vital signs, physical examination
• Mental status examination
• Basic laboratory, such as blood and urine tests
• MRI or CT scan of the affected region
• Lumbar puncture and collection of cerebrospinal fluid for analysis
• Electroencephalogram (EEG)

Neuroleptic Malignant Syndrome is often tentatively diagnosed on clinical suspicion, when no other disease or condition explains it, and when intoxication is ruled out. And, it can be presumptively treated if suspicion is high based on available evidence, if waiting may lead to poorer outcomes.  

Many clinical conditions can have similar signs and symptoms.  Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.  

What are the possible Complications of Neuroleptic Malignant Syndrome?

Complications of Neuroleptic Malignant Syndrome include:

• Tissue hypoxia (insufficient delivery of oxygen to the tissues)
• Dehydration
• Seizures
• Hyperkalemia (elevated blood levels of potassium)
• Metabolic acidosis (accumulation of acids in blood)
• Deep vein clots
• Renal (kidney) insufficiency or failure
• Liver insufficiency or failure

Other complications of Neuroleptic Malignant Syndrome can include:

• Intolerance to future use of neuroleptic and antipsychotic medications (observed in about 13% of the individuals)
• Cardiac arrhythmias
• Complications may occur with or without treatment, and due to treatment also

How is Neuroleptic Malignant Syndrome Treated?

Initial and immediate treatment of Neuroleptic Malignant Syndrome involves discontinuation of the offending medication.  If this step in combination with other treatment measures does not begin to help, the healthcare provider might consider other diagnoses.  

Other treatments for Neuroleptic Malignant Syndrome may include:

• Maintenance of appropriate fluid and electrolyte (salt) levels through an intravenous line
• Aggressive fever control through cooling blankets or axillary ice packs and sometimes antipyretics (medications)
• Administration of muscle relaxants, dopamine-stimulating medications, and often, central nervous system depressants
• Administration of anti-arrhythmic medications (for the heart) and anticoagulants to prevent clotting
• Electroconvulsive therapy has been used in some individuals with varied results

How can Neuroleptic Malignant Syndrome be Prevented?

No confirmed methods for prevention of Neuroleptic Malignant Syndrome have been established.  

What is the Prognosis of Neuroleptic Malignant Syndrome? (Outcomes/Resolutions)

If treated promptly and properly, Neuroleptic Malignant Syndrome has a generally good prognosis. Most cases resolve completely within 2 weeks, with a mean time to recovery of 7 to 11 days.

• The majority of individuals (87% by one study’s estimation) are able to tolerate neuroleptic medicines again in the future. However, usually a less potent choice is made (often an “atypical antipsychotic”), and nearly always a different choice from what the individual was taking earlier, when he/she experienced the condition. The new medication is typically introduced slowly, that is, with gradual dose increases
• Mortality rates for Neuroleptic Malignant Syndrome are estimated at 5-20%, with disease severity and occurrence of medical complications as predictors

Additional and Relevant Useful Information for Neuroleptic Malignant Syndrome:

Elevated heart rate (tachycardia) is seen in the vast majority of cases of Neuroleptic Malignant Syndrome; blood pressure is labile and can go either way. If blood pressure is low, it must be corrected quickly to avoid anoxic brain injury, in which the blood pressure is insufficient to deliver oxygen to the vital tissues of the brain.  This correction and control of blood pressure can be accomplished in a hospital setting.

NMS is similar in presentation to malignant hyperthermia, a genetic condition which causes individuals to react severely to certain inhaled anesthetic gases.