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The neuroleptic malignant syndrome is a rare neurological disorder that occurs due to the side effects of neurological agents such as sedatives, hypnotics, anti-depressant drugs and anti-psychotic drugs. These agents alter the brain functions and the response to certain brain impulses, thus causing altered neurological action.

The neuroleptic malignant syndrome is usually characterized by high fever, muscle stiffness, and altered mental status. It may also prove to be life-threatening when this condition is not diagnosed or treated at an early stage.

A major number of neuroleptic malignant syndrome cases are reported in the first week of use of neuroleptic agents with a higher number of cases reported in men when compared to women population.


The symptoms of neuroleptic malignant syndrome include:


  • High fever
  • Muscle stiffness
  • Altered heart rate
  • Increased heart rate
  • Increased breathing
  • Increased sweating
  • Unusual pale appearance of the skin
  • Difficulty in swallowing food
  • Urinary incontinence
  • Tremors
  • Altered blood pressure


In severe conditions, the neuroleptic malignant syndrome may also produce symptoms such as:


  • Liver and kidney impairment
  • Increased risk of clot formation in the blood vessels
  • Increased blood potassium levels
  • Increased risk of destruction of the skeletal muscles
  • Altered autonomic system functions



The neuroleptic malignant syndrome occurs due to the change in the neurotransmitter levels in the brain majorly due to dopamine D2 receptor antagonism. The dopamine D2 receptor is found in abundance in the central nervous system that helps in the effective cell to cell communication.

A decrease in the dopamine levels in the brain causes increased muscle rigidity and also increases the body temperature and alters mood swings when they come in contact with the hypothalamus.

Certain studies also prove neuroleptic malignant syndrome to occur due to a genetically related disorder called malignant hyperthermia that causes adverse reactions due to anesthetic drugs.

Risk factors

The risk of developing neuroleptic malignant syndrome increases with the following factors:


  • High dose of neuroleptic agents
  • Use of highly potent neuroleptic agents
  • Long-term use of neuroleptic agents
  • A sudden increase in the dose of neuroleptic agents
  • Long half-life of certain neuroleptic agents
  • A previous history of neuroleptic malignant syndrome
  • Irregular use of neuroleptic agents


The other possible risk factors include:


  • Dehydration
  • Lithium use
  • Malnutrition
  • Non-schizophrenic mental disorders
  • Organic brain syndrome
  • Post-partum period
  • Sudden increase in humid or warm environment


The possible complications that arise due to neuroleptic malignant syndrome include:


  • Cardiac arrhythmias
  • Deep vein thrombosis
  • Heart failure
  • Hepatic failure
  • Pneumonia
  • Psychiatric disorders
  • Renal failure
  • Respiratory failure
  • Rhabdomyolysis


The diagnosis of neuroleptic malignant syndrome is based on the physical finding, previous family history, laboratory parameters and image scans.

The physical findings help in determining the cause of neuroleptic malignant syndrome causes such as muscle rigidity, high fever, cognitive impairment and other vital signs.


  • Image scan: Imaging scan such as magnetic resonance imaging (MRI) scan and computed tomography (CT) scan helps in diagnosing the affected area of the brain and the underlying cause of the condition such as head injury, stroke or tumor formation.
  • Lumbar puncture: The test involves the collection of cerebrospinal fluid (CSF) by injecting a needle into the spinal cord. The occurrence of neuroleptic malignant syndrome can be detected by a change in the consistency of cerebrospinal fluid.
  • Laboratory parameters: Blood, urine samples, liver function test, creatine kinase and serum electrolytes are collected that helps in assessing the severity of the condition.
  • Electroencephalogram: This test studies the electrical activity of the brain by placing electrodes over the scalp. The brain’s impulses produced are recorded that helps in determining the severity of neuroleptic malignant syndrome.



The initial treatment followed to treat neuroleptic malignant syndrome includes discontinuing the use of dopaminergic agonist drugs. This is followed by use of nutrient and fluid replenishment that helps in faster recovery from the condition.

The use of anti-pyretic agents and muscle relaxants are used to treat hyperthermia and muscle rigidity respectively. Other medication may also include drugs to increase the dopamine levels in the brain, antidepressant and anticonvulsive agents.

The treatment of neuroleptic malignant syndrome should include supportive care to prevent the risk of liver and kidney impairment.


Neuroleptic malignant syndrome can be managed by the effective use of medications. A large group of people showed better tolerance to neuroleptic agents post-treatment. It was also effectively managed by using less potent neuroleptic agents.



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