Table of ContentsView AllTable of ContentsSymptomsCausesDiagnosisTreatment
Table of ContentsView All
View All
Table of Contents
Symptoms
Causes
Diagnosis
Treatment
Neuroleptic malignant syndrome (NMS) is a rare and life-threatening condition that can occur after changes in specific medications, most commonly after increases in psychiatric drugs.
NMS was first characterized during the 1960s, soon after the introduction of the first antipsychotic drugs. Fortunately, NMS is less common than it used to be. This is partly due to the introduction of newer “second-generation” antipsychotic drugs, which are less likely to cause the syndrome.NMS can occur in people of all ages, and it seems to be more common in males than in females.
This article discusses the symptoms and causes of NMS, as well as how it is diagnosed and treated.
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What Are the Symptoms of Neuroleptic Malignant Syndrome?
The symptoms of NMS may start out gradually and worsen over a few days. Two of the classic symptoms of NMS are muscular rigidity and high fever. Other potential symptoms include:
Other symptoms may include liver or kidney failure, abnormally high potassium levels (hyperkalemia), major destruction of skeletal muscle tissue (rhabdo-myolysis), or blood clots in veins and arteries.
Not everyone with NMS will have all of these symptoms. For example, muscle rigidity and elevated body temperature may not occur in someone with NMS from an “atypical” antipsychotic drug. NMS may be more difficult to diagnose in someone without these classic symptoms.
Unfortunately, if not diagnosed and treated promptly, NMS can cause death (from respiratory failure, heart rhythm abnormalities, or other problems).
What Causes Neuroleptic Malignant Syndrome?
Dopamine System
Conditions such asParkinson’s diseasehave other problems with dopamine production and stimulation.
Drugs Affecting Dopamine and NMS
Both schizophrenia and Parkinson’s disease are sometimes treated with drugs that affect the dopamine system. In rare circumstances, sudden changes in medications that either block or stimulate dopamine receptors can lead to the symptoms of NMS. Researchers still aren’t sure why only a small percentage of people taking these drugs develop NMS.
Most commonly, NMS occurs after a person is given a drug that blocks dopamine receptors. An example is the drug haloperidol, used to help treat schizophrenia and some other psychiatric conditions.Drugs like haloperidol can have positive effects, such as reducinghallucinations. However, in NMS, something triggers a side effect from the drug.
NMS is more likely to occur after sudden changes in these drugs, such as:
Less commonly, NMS can occur when a person is on a long-term stable dose of a drug such as haloperidol.
NMS is more common with older “typical” antipsychotics like haloperidol. However, more recently developed antipsychotic drugs (sometimes called “atypical” antipsychotics) may also trigger NMS in certain situations.
Other types of drugs that affect dopamine receptors can also cause NMS. For example, certain drugs to prevent vomiting (such asmetoclopramide) also block certain dopamine receptors. Sometimes increasing these drugs can lead to NMS.
In other cases, NMS can occur after a drug is stopped or dramatically decreased. Drugs such as levodopa can be given to helpincreasedopamineproduction. For example, levodopa can be used to treat someone with Parkinson’s disease. If a person stops, steps down, or switches these types of medications, NMS might occur.
NMS has its greatest potential risk whenincreasingthe dose of a dopamine-blocking drug (like haloperidol) ordecreasingthe dose of a dopamine-stimulating drug. In both cases, a person is receiving less dopamine stimulation than before.
Exactly why this can trigger NMS is still unclear. It probably involves a complex series of physiological events. The abrupt change in stimulation to dopamine receptors seems to dysregulate theautonomic nervous system(part of your body that regulates many unconscious bodily functions). This is what leads to problems such as increased pulse and breathing rate. Changes in dopamine may also lead to unexpected effects on muscle cells, triggering muscular rigidity.
These are some of the other drugs that can cause NMS whenincreased:
Other drugs that stimulate dopamine (like amantadine) may trigger NMS whendecreasedor removed.
How Is NMS Diagnosed?
The diagnosis of NMS is sometimes difficult, as it can resemble other conditions. For example, healthcare providers must rule out medical problems that may have some similar symptoms, like heat stroke, central nervous system infection, or drug intoxication.
The clinical exam and medical history provide important starting points. Critically, NMS is only a possibility if the individual is taking one of the medications that can lead to NMS.
Fortunately, due to greater awareness of the condition, people tend to be diagnosed sooner than they were in the past. This has reduced long-term effects and death rates from the syndrome.
Treatment for Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome is a medical emergency and it must be treated as quickly as possible. Affected individuals need close monitoring in an intensive care unit.
In the majority of cases, NMS can be managed successfully and the affected person will recover within a couple of weeks with no long-term consequences. However, sometimes there are permanent problems related to NMS, such as kidney failure.
NMS is fatal in roughly 10% of cases (with higher rates in the elderly and in people with other significant medical conditions, like congestive heart failure).
Monitoring for NMS
Unfortunately, there isn’t a way to predict which people who start these types of drugs will experience NMS. Genetic factors may play a role, but these are not yet known.
It is important to be aware of the condition if you or someone you care about is taking a medication with a risk of triggering NMS. It is important to monitor people who have recently started dopamine-blocking drugs for early symptoms. This is especially important for people who have started injectable, long-acting medications.
It is also important to monitor people with Parkinson’s disease who are stopping medication or changing their treatment regimen. This careful monitoring can lead to early diagnosis and treatment.
After Neuroleptic Malignant Syndrome
Although most people who experience NMS never have another episode, some people may, especially if proper precautions are not followed.
If a person experiences NMS, it is important not to restart a similar drug too soon. Generally speaking, one needs to wait at least a couple of weeks before resuming treatment. Then your healthcare provider can slowly reintroduce a drug with careful monitoring. Typically, people are started on a related drug that is not the same one originally associated with triggering NMS.
What to DoIf you are concerned about NMS or a recurrence of NMS, talk to your healthcare provider. Don’t stop taking medications without first consulting your treatment team—that might lead to other major problems.However, you may be able to use another medication with a lower risk of NMS. For example, you might be able to switch from an older drug to a newer “atypical” antipsychotic drug. Or you might be able to use a lower dose of the drug you are taking, lowering the risk of NMS. Be sure to discuss any concerns with your healthcare team.
What to Do
If you are concerned about NMS or a recurrence of NMS, talk to your healthcare provider. Don’t stop taking medications without first consulting your treatment team—that might lead to other major problems.However, you may be able to use another medication with a lower risk of NMS. For example, you might be able to switch from an older drug to a newer “atypical” antipsychotic drug. Or you might be able to use a lower dose of the drug you are taking, lowering the risk of NMS. Be sure to discuss any concerns with your healthcare team.
If you are concerned about NMS or a recurrence of NMS, talk to your healthcare provider. Don’t stop taking medications without first consulting your treatment team—that might lead to other major problems.
However, you may be able to use another medication with a lower risk of NMS. For example, you might be able to switch from an older drug to a newer “atypical” antipsychotic drug. Or you might be able to use a lower dose of the drug you are taking, lowering the risk of NMS. Be sure to discuss any concerns with your healthcare team.
Summary
6 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Berman BD.Neuroleptic malignant syndrome: a review for neurohospitalists.The Neurohospitalist. 2011;1(1):41-47. doi:10.1177/1941875210386491Simon LV, Hashmi MF, Callahan AL.Neuroleptic Malignant Syndrome. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.Brisch R, Saniotis A, Wolf R, et al.The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue.Front Psychiatry. 2014;5:47. doi:10.3389/fpsyt.2014.00047Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatric Disease and Treatment. 2017;13:161-175. doi:10.2147/NDT.S118438Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatr Dis Treat. 2017;13:161-175. doi:10.2147/NDT.S118438Tormoehlen LM, Rusyniak DE.Neuroleptic malignant syndrome and serotonin syndrome.Handb Clin Neurol. 2018;157:663-675. doi:10.1016/B978-0-444-64074-1.00039-2
6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Berman BD.Neuroleptic malignant syndrome: a review for neurohospitalists.The Neurohospitalist. 2011;1(1):41-47. doi:10.1177/1941875210386491Simon LV, Hashmi MF, Callahan AL.Neuroleptic Malignant Syndrome. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.Brisch R, Saniotis A, Wolf R, et al.The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue.Front Psychiatry. 2014;5:47. doi:10.3389/fpsyt.2014.00047Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatric Disease and Treatment. 2017;13:161-175. doi:10.2147/NDT.S118438Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatr Dis Treat. 2017;13:161-175. doi:10.2147/NDT.S118438Tormoehlen LM, Rusyniak DE.Neuroleptic malignant syndrome and serotonin syndrome.Handb Clin Neurol. 2018;157:663-675. doi:10.1016/B978-0-444-64074-1.00039-2
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Berman BD.Neuroleptic malignant syndrome: a review for neurohospitalists.The Neurohospitalist. 2011;1(1):41-47. doi:10.1177/1941875210386491Simon LV, Hashmi MF, Callahan AL.Neuroleptic Malignant Syndrome. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.Brisch R, Saniotis A, Wolf R, et al.The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue.Front Psychiatry. 2014;5:47. doi:10.3389/fpsyt.2014.00047Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatric Disease and Treatment. 2017;13:161-175. doi:10.2147/NDT.S118438Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatr Dis Treat. 2017;13:161-175. doi:10.2147/NDT.S118438Tormoehlen LM, Rusyniak DE.Neuroleptic malignant syndrome and serotonin syndrome.Handb Clin Neurol. 2018;157:663-675. doi:10.1016/B978-0-444-64074-1.00039-2
Berman BD.Neuroleptic malignant syndrome: a review for neurohospitalists.The Neurohospitalist. 2011;1(1):41-47. doi:10.1177/1941875210386491
Simon LV, Hashmi MF, Callahan AL.Neuroleptic Malignant Syndrome. [Updated 2023 Apr 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
Brisch R, Saniotis A, Wolf R, et al.The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue.Front Psychiatry. 2014;5:47. doi:10.3389/fpsyt.2014.00047
Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatric Disease and Treatment. 2017;13:161-175. doi:10.2147/NDT.S118438
Oruch R, Pryme IF, Engelsen BA, Lund A.Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.Neuropsychiatr Dis Treat. 2017;13:161-175. doi:10.2147/NDT.S118438
Tormoehlen LM, Rusyniak DE.Neuroleptic malignant syndrome and serotonin syndrome.Handb Clin Neurol. 2018;157:663-675. doi:10.1016/B978-0-444-64074-1.00039-2
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