A life-threatening and rare condition that causes a reaction to certain medicines called neuroleptic (also known as antipsychotic) medicines is called neuroleptic malignant syndrome (NMS). In most cases, it causes high fever and muscle stiffness. If any of the previous symptoms occur, immediately call 911 or go to the nearest emergency room (ER).
In other words, some people may have a reaction to antipsychotic (neuroleptic) medicines that are used to manage the symptoms of multiple psychiatric conditions. In general, this disorder is characterized by high fever (also known as hyperthermia), rigid and stiff muscles (in some cases, it may lead to muscle breakdown), altered mental status, and autonomic nervous system dysfunction (dysautonomia).
Normally, the autonomic nervous system is responsible for regulating some processes in the body. For example, blood pressure, rate of breathing, and others. If this system works improperly, it may lead to swings in blood pressure, excessive sweating (also known as secondary hyperhidrosis), and excessive secretion of saliva.
Neuroleptic Medicines
This group of medicines falls into 2 types: first-generation or “typical” antipsychotics and second-generation or “atypical” antipsychotics. Doctors often prescribe them to manage the symptoms and treat the following conditions. Examples include:
- Bipolar disorder
- Major depressive disorder
- Eating disorders
- Behavioral disturbances in people with dementia
- Generalized anxiety disorder
- Geriatric agitation
- Obsessive-compulsive disorder (OCD)
- Personality disorders
- Sleep disturbances (insomnia)
- Post-traumatic stress disorder (PTSD)
- Schizoaffective disorder
- Schizophrenia and others
What Antipsychotic Medicines are Associated with NMS?
Check some examples of typical neuroleptic (antipsychotic) medicines below:
- Bromperidol
- Chlorpromazine
- Clopenthixol
- Fluphenazine
- Loxapine
- Thiothixene
- Trifluoperazine
- Promazine
- Haloperidol and others
Check also some examples of atypical neuroleptic medicines below:
- Clozapine
- Olanzapine
- Ziprasidone
- Zotepine
- Risperidone
- Aripiprazole
- Amisulpride and others
Antiemetic Medicines
- Domperidone
- Metoclopramide
- Promethazine
- Droperidol
Dopaminergic Medicines
The following medicines are often prescribed by doctors to manage the symptoms of Parkinson’s disease. For example:
- Tolcapone
- Levodopa
- Dopamine agonists
- Amantadine
Any of the previous medications increases your risk of developing NMS. Consult with your doctor before taking any of them.
How Common is Neuroleptic Malignant Syndrome?
Generally, this condition occurs rarely, and it affects about 0.1% to 3.2% of people who administer antipsychotic medicines. Moreover, the NMS cases are decreasing because of new medicines that are less likely to cause it.
What is The Difference between Neuroleptic Malignant Syndrome and Malignant Hyperthermia?
While the symptoms of both conditions are similar, malignant hyperthermia occurs due to a severe reaction to general anesthesia drugs and muscle relaxants. Usually, people experience muscle stiffness or rigidity, decreased reflexes, and skin changes (including bluish discoloration or flushing).
Symptoms
People who develop NMS often notice the symptoms within 1-3 days. Check some examples below:
- Tachycardia (fast heart rate)
- Arrhythmia (irregular heart rhythm)
- High fever (102 to 104 degrees F)
- Fast breathing (also known as tachypnea)
- Altered mental status
- Hypertension (high blood pressure) or hypotension (low blood pressure)
- Excessive sweating
Immediately visit a doctor if any of the symptoms listed above occur.
Causes and Risk Factors
This serious condition may occur from a single dose, an increasing dose, or the same dose of neuroleptic (antipsychotic) medicine. Commonly, it is associated with first-generation antipsychotics, but it may happen with second-generation neuroleptics, antiemetics, and withdrawal of anti-Parkinson or dopaminergic medicines.
Nowadays, research is ongoing to understand what exactly causes NMS. Currently, experts know that it is caused by dopamine D2 receptor antagonism, which is a neurotransmitter that acts to convey messages from one cell to another. When you are administering neuroleptics, these messenger is blocked. Moreover, when dopamine receptors are located in the hypothalamus or spinal cord, it may lead to muscle stiffness.
While anyone who takes antipsychotics may develop NMS, there are some factors that could increase your risk of developing it. For example:
- Dehydration
- Agitation
- Exhaustion
- Prolonged heat exposure
- Some existing health conditions (including organic brain disorders, previous history of NMS, and others)
What Happens if Neuroleptic Malignant Syndrome is Left Untreated?
People who ignore the symptoms of NMS and do not get treatment may experience the following complications. These include:
- Rhabdomyolysis (this is one of the most common complications in people with NMS)
- Acute kidney failure
- Seizures
- Myocardial infarction (also known as a heart attack)
- Blood clots throughout the body (disseminated intravascular coagulation)
- Acute liver or kidney failure
- Pneumonia
- Sepsis
- Urinary tract infections (UTIs)
- Pulmonary embolism (a blood clot in the lungs)
If you notice any of the previous complications, immediately call 911 or go to the nearest emergency room. Otherwise, it may lead to permanent damage or even death. Furthermore, this article does not contain a complete list of NMS complications. In any case, you can talk with your doctor about ways to reduce the risk or even prevent them.
How to Prevent Neuroleptic Malignant Syndrome?
To reduce the risk of NMS, you should manage some risk factors. For instance, administer antipsychotics exactly as prescribed by your doctor. It means you should not lower, increase, or double the dosage without your doctor’s approval. For more details, discuss it with your physician.
Diagnosis
To confirm this condition, you must have all of the following symptoms or conditions. Examples include:
- You are administering neuroleptic medicines
- Suddenly stopped a dopaminergic medicine
- Severe muscle rigidity
- High fever
- Altered mental status
Additionally, people with NMS must have at least 2 of the following symptoms. These include:
- Swallowing problems
- Inability to speak that occurs suddenly
- Increased or frequent fluctuation of the blood pressure
- Leukocytosis (increased white blood cell count)
- Fast heart rate (tachycardia)
- Incontinence
- Excessive or abnormal sweating
- Increased creatine phosphokinase (CPK) caused by muscle breakdown
- Hyporeflexia (slow or limited reflexes)
Furthermore, doctors may also perform some tests to get more clues about the disease. Check some examples below:
- Urinalysis (blood tests)
- CPK (creatine phosphokinase) blood test
- Comprehensive metabolic panel
- Arterial or venous blood gas test
Treatment
This is a life-threatening condition that requires immediate treatment. Otherwise, it may lead to permanent damage or even death. Check below some treatment options recommended for people with NMS:
- Mechanical ventilation, antiarrhythmic medicines, or pacemakers to maintain cardiorespiratory stability
- Intravenous (IV) fluids to prevent electrolyte imbalance
- Cooling blankets and ice water or packs to reduce fever
- Medicines to regulate blood pressure
- Anticoagulants (also known as blood thinners) to treat or prevent blood clots
- Muscle and skeletal relaxants
Frequently Asked Questions
What is the prognosis for neuroleptic malignant syndrome?
While people who get immediate treatment often recover within 14 days, delayed treatment may lead to some serious complications. For example, muscle, kidney, heart, and lung problems. In general, the mortality rate ranges between 5% and 20%, especially if it is not treated quickly.
When should I go to the ER?
If you experience high fever and muscle stiffness, you should call 911 or go to the nearest emergency room (ER). Otherwise, the morality rate significantly increases.
What is the difference between neuroleptic malignant syndrome and serotonin syndrome?
While serotonin syndrome is caused by serotonergic agents (including antidepressants, antihistamines, mood stabilizers, and amphetamines), neuroleptic malignant syndrome appears due to a reaction to antipsychotic medicines. Usually, physicians can distinguish these disorders based on the symptoms and your medical history. Ask your healthcare provider if you have additional questions.
