Neuroleptic Malignant Syndrome

What is Neuroleptic Malignant Syndrome?

Neuroleptic malignant syndrome (NMS) is a severe, life-threatening condition that can occur when taking specific medications that affect dopamine, a chemical in your brain. It can also happen if these types of drugs are stopped too quickly. This syndrome has been linked to almost all neuroleptic drugs but is more commonly reported with typical antipsychotics like haloperidol and fluphenazine. Key symptoms of NMS include changes in mental state, fever, muscle stiffness, and instability of the autonomic nervous system, which controls body functions like heart rate and temperature.

Although NMS is not very common, it’s important to consider it as a possible diagnosis when someone has a fever and changes in mental state, as early diagnosis and treatment are crucial to prevent severe health outcomes or even death. Treatment involves immediately stopping the culprit medication, robust supportive care to handle and prevent further complications, and in severe cases, medication.

The go-to medications often used for severe NMS include bromocriptine mesylate, a drug that boosts dopamine levels, and dantrolene sodium, a muscle relaxant. If the syndrome is due to abruptly stopping dopaminergic medication, quickly resuming the medication may improve symptoms.

What Causes Neuroleptic Malignant Syndrome?

Neuroleptic Malignant Syndrome (NMS) is mostly caused by a blockage of dopamine receptors in the brain, usually because of certain types of drugs. These drugs are most commonly antipsychotic agents, but could also be various other types of drugs such as antidepressants, antiemetic drugs (used to control nausea and vomiting), or even drugs like lithium. NMS can also be triggered by the sudden stopping of certain drugs used to manage Parkinson’s disease, like levodopa and amantadine, or rapidly switching from one Parkinson’s medication to another.

Certain medications are commonly associated with causing NMS. These include:

Traditional antipsychotics: Drugs like Haloperidol, Chlorpromazine, Fluphenazine, and more.
Modern (atypical) antipsychotics: Drugs like Olanzapine, Clozapine, Risperidone, and more.
Antiemetic drugs: Drugs like Droperidol, Domperidone, and Metoclopramide, among others.
Other drugs: This can include Tetrabenazine, Reserpine, Amoxapine, Diatrizoate, and others
Drugs for Parkinson’s diseases, when suddenly stopped, like Levodopa, Amantadine, Tolcapone, and dopamine agonists (drugs that simulate the actions of dopamine in the brain) can also cause NMS.

Risk Factors and Frequency for Neuroleptic Malignant Syndrome

The chances of developing Neuroleptic Malignant Syndrome (NMS), a condition linked to certain medications, range from 0.01% to 3.2% for those taking the related drugs. These rates are going down, thanks to newer medications that are less likely to cause NMS and increased knowledge about the condition. NMS often occurs in young adults, but this is more linked with the age at which they first take these medications rather than any age-related risk. Men are twice as likely as women to develop NMS, again due to their likelihood of taking these medications. Seniors are more likely to develop NMS due to stopping the intake of certain drugs, based on their chances of getting such medications.

The risk of developing Neuroleptic Malignant Syndrome ranges from 0.01% to 3.2% for people on specific medications.
The incidence of this condition is decreasing due to the development of new, safer drugs and increased awareness.
It is most common in young adults, but this is linked to the age at which they first start taking such medications, not an age-specific risk.
Men are twice as likely to develop this condition, again because they are more likely to be on these medications.
Stopping certain medications in older people raises the chances of developing the condition.

Signs and Symptoms of Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a potentially dangerous reaction to certain medications used to treat mental disorders. The primary risk factor for NMS is starting or increasing the dosage of these medications, specifically those that are high-potency, long-lasting, or that are used in combination with other similar drugs or lithium. Additionally, suddenly stopping the use of drugs that affect dopamine in the brain can cause NMS. Symptoms of NMS, which usually appear within three days, include fever, stiff muscles, changes in mental state, and autonomic dysfunction, which can affect many bodily systems.

The diagnosis is typically made based on the following criteria, as outlined by the DSM-V:

All of the following major criteria must be met:
- Exposure to a medication that blocks dopamine
- Severe muscle rigidity
- Fever
Plus, at least two of the following additional criteria are required:
- Sweating excessively (diaphoresis)
- Difficulty swallowing (dysphagia)
- Shaking (tremor)
- Loss of bladder control (incontinence)
- Changes in consciousness
- Inability to speak (mutism)
- Fast heart rate (tachycardia)
- High or unstable blood pressure
- Unusually high white blood cell count (leukocytosis)
- Elevated creatine phosphokinase, a type of enzyme

Testing for Neuroleptic Malignant Syndrome

If your doctor suspects you have rhabdomyolysis, a condition where muscle tissue breaks down and releases into the blood, they will plan a broad set of tests. These tests include checking your electrolytes and creatinine levels, both of which show how well your kidneys are functioning. Another test, called creatine phosphokinase level, is used to measure damage or stress in the muscles. Moreover, a urinalysis test might be performed to check for the presence of myoglobin, a protein from muscle, in your urine. Finally, a blood gas test can help determine the levels of gases and pH in your blood and check for acidosis, a condition when your body fluids contain too much acid.

While your doctor can sometimes diagnose rhabdomyolysis based on your symptoms, these lab tests bolster the diagnosis. Often, these tests will indicate high levels of creatine kinase, an enzyme found in the heart, brain, and skeletal muscle, and a sudden decrease in kidney function.

The level of creatine kinase can significantly elevate and usually parallels the severity of your condition. An increase in white blood cells between 10,000 and 40,000 mm3 is common, which means your immune system is working hard against infection or disease. Additionally, you may also have slightly higher levels of liver enzymes called transaminases, a possible indicator of liver damage.

In unclear cases, your doctor may need to conduct additional tests. These can include neuroimaging to look at your brain’s structure and a lumbar puncture to test your spinal fluid. For certain patients, they might also run tests to check for drug abuse or lithium level, a medication used for certain mental health conditions.

Treatment Options for Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a serious neurological condition that requires immediate medical attention. If not diagnosed and treated quickly, this syndrome can cause severe health issues or even death. The first and most important step in treatment is to stop taking the medication that triggered the condition.

After stopping the medication, doctors next focus on helping the patient continue to function normally. They do this through supportive therapy, which involves trying to keep the patient’s body cool, replacing any fluids they lost and managing any imbalances in electrolytes – minerals in the body that help nerves and muscles function properly.

Patients with NMS are also at risk of heart rhythm problems, also known as cardiac dysrhythmias, and potentially they could have difficulty breathing due to stiffness in the chest wall. Doctors typically address these risks with heart medication or even use of a machine to help the patient breathe.

For more severe cases of NMS, additional drug treatments might be necessary. Bromocriptine, a drug that increases the activity of dopamine, a chemical used by nerve cells to communicate, can be given orally or via a gastric tube to help correct lower-than-normal dopamine levels. Dantrolene, a muscle relaxant, may also be given, either through a vein or orally in less-severe cases. Benzodiazepines, which are medications that calm agitation, may also be used to manage additional symptoms.

If NMS is caused by stopping a medication that increases dopamine levels, then restarting the same medication can sometimes ease symptoms. If NMS is very severe and not responding to other treatments, then electroconvulsive therapy, which sends controlled electric current into the brain, might also be considered a treatment option. Regardless of the specific treatments used, it is crucial to monitor patients closely, preferably in an intensive care unit, to ensure their safety.

Neuroleptic Malignant Syndrome (NMS) is a medical condition sometimes caused by a reaction to certain medications, resulting in symptoms like fever, muscle stiffness, and issues with how our bodies regulate heart rate, breathing, and other automatic functions. Conditions with similar symptoms include Serotonin Syndrome – often caused by medications used for depression, Malignant Hyperthermia – typically triggered by certain anaesthetics, and Malignant Catatonia – that also includes symptoms of altered mental status. It’s important to note a key difference between NMS and Malignant Catatonia; the latter often responds well, with a high recovery rate, to treatment with medications like benzodiazepines and electroconvulsive therapy.

There are many other conditions which can resemble NMS, making it occasionally difficult to accurately diagnose. These include:

Infections that affect the brain and spinal cord, such as meningitis or encephalitis.
Heatstroke
Mental confusion due to overstimulation (agitated delirium)
Chemically or organically caused changes in brain function (toxic encephalopathies)
Withdrawal symptoms from stopping certain drugs
Metabolic emergencies
Continuous, non-convulsive seizures (nonconvulsive status epilepticus).

When a patient has symptoms like fever and changes in mental status, it’s crucial to rule out conditions such as acute encephalitis, meningitis, or brain abscess to avoid delay in potentially life-saving treatment. Patients on antipsychotic medications have a higher risk of heat-related illnesses, which may also resemble NMS. Additionally, certain recreational drugs can cause similar symptoms. Withdrawal from certain muscle relaxants, alcohol, and sedative drugs can also mimic NMS. It’s important to be aware that certain conditions related to the thyroid and adrenaline-producing glands can also resemble NMS.

What to expect with Neuroleptic Malignant Syndrome

Previously, the mortality rate for Neuroleptic Malignant Syndrome (NMS), a serious reaction to antipsychotic drugs, was higher than 30%. However, due to increased awareness, earlier detection, and better supportive care, the mortality rate has dropped to less than 10%. When NMS is recognized early and treated aggressively, most patients generally recover fully in about 2 to 14 days.

Delayed treatment could result in severe health complications like lasting catatonia (a state of unresponsiveness), Parkinson’s disease symptoms, or damage to the kidneys or heart and lungs. Fatalities from NMS usually occur from irregular heartbeats, blood clotting throughout the body, respiratory failure, or kidney failure.

Many patients can successfully start taking antipsychotic medication again, but some may experience recurring symptoms. Guidelines suggest waiting at least two weeks after symptoms have disappeared before restarting these medications. It’s also recommended to use less potent drugs, start with low doses and gradually increase as needed, and avoid using lithium with these medications.

Patients should be advised to prevent dehydration and should be continuously monitored for any signs of NMS recurrence.

Frequently asked questions

When Neuroleptic Malignant Syndrome (NMS) is recognized early and treated aggressively, most patients generally recover fully in about 2 to 14 days. The mortality rate for NMS has dropped to less than 10% due to increased awareness, earlier detection, and better supportive care. However, delayed treatment could result in severe health complications and fatalities from NMS usually occur from irregular heartbeats, blood clotting throughout the body, respiratory failure, or kidney failure.

Neuroleptic Malignant Syndrome (NMS) is mostly caused by a blockage of dopamine receptors in the brain, usually because of certain types of drugs. These drugs are most commonly antipsychotic agents, but could also be various other types of drugs such as antidepressants, antiemetic drugs (used to control nausea and vomiting), or even drugs like lithium. NMS can also be triggered by the sudden stopping of certain drugs used to manage Parkinson's disease, like levodopa and amantadine, or rapidly switching from one Parkinson's medication to another.

The signs and symptoms of Neuroleptic Malignant Syndrome (NMS) include: - Fever - Severe muscle rigidity - Changes in mental state - Autonomic dysfunction, which can affect many bodily systems - Excessive sweating (diaphoresis) - Difficulty swallowing (dysphagia) - Shaking (tremor) - Loss of bladder control (incontinence) - Changes in consciousness - Inability to speak (mutism) - Fast heart rate (tachycardia) - High or unstable blood pressure - Unusually high white blood cell count (leukocytosis) - Elevated creatine phosphokinase, a type of enzyme These symptoms typically appear within three days of starting or increasing the dosage of medications that block dopamine or suddenly stopping the use of drugs that affect dopamine in the brain. It is important to note that NMS is a potentially dangerous reaction to certain medications used to treat mental disorders, and immediate medical attention should be sought if these symptoms occur.

The types of tests needed for Neuroleptic Malignant Syndrome include: - Neuroimaging to look at the brain's structure - Lumbar puncture to test the spinal fluid - Tests to check for drug abuse or lithium levels - Monitoring of electrolytes and creatinine levels to assess kidney function - Blood gas test to determine levels of gases and pH in the blood and check for acidosis - Creatine phosphokinase level test to measure muscle damage or stress - Urinalysis to check for the presence of myoglobin in the urine - Monitoring of white blood cell count and liver enzyme levels.

Infections that affect the brain and spinal cord, such as meningitis or encephalitis. Heatstroke Mental confusion due to overstimulation (agitated delirium) Chemically or organically caused changes in brain function (toxic encephalopathies) Withdrawal symptoms from stopping certain drugs Metabolic emergencies Continuous, non-convulsive seizures (nonconvulsive status epilepticus). Acute encephalitis, meningitis, or brain abscess Heat-related illnesses Recreational drugs Withdrawal from certain muscle relaxants, alcohol, and sedative drugs Conditions related to the thyroid and adrenaline-producing glands

When treating Neuroleptic Malignant Syndrome (NMS), there can be side effects such as heart rhythm problems (cardiac dysrhythmias) and difficulty breathing due to stiffness in the chest wall. To address these risks, doctors may use heart medication or a machine to assist with breathing. Additionally, there may be side effects from the drug treatments used for NMS, including Bromocriptine (increased dopamine activity), Dantrolene (muscle relaxant), and Benzodiazepines (calming agitation). It is important to closely monitor patients, preferably in an intensive care unit, to ensure their safety.

A neurologist or a psychiatrist.

The risk of developing Neuroleptic Malignant Syndrome ranges from 0.01% to 3.2% for people on specific medications.

Neuroleptic Malignant Syndrome (NMS) is treated by first stopping the medication that triggered the condition. After that, doctors focus on supportive therapy to help the patient function normally. This includes keeping the patient's body cool, replacing lost fluids, and managing electrolyte imbalances. Patients with NMS may also receive heart medication or assistance with breathing. In more severe cases, additional drug treatments such as bromocriptine, dantrolene, or benzodiazepines may be necessary. Restarting the same medication that caused NMS can sometimes ease symptoms. In very severe cases, electroconvulsive therapy may be considered. Close monitoring in an intensive care unit is crucial for patient safety.

Neuroleptic Malignant Syndrome (NMS) is a severe, life-threatening condition that can occur when taking certain medications that affect dopamine in the brain, or if these medications are stopped abruptly. It is characterized by changes in mental state, fever, muscle stiffness, and instability of the autonomic nervous system.