Recognizing and Managing Neuroleptic Malignant Syndrome

  • Neuroleptic malignant syndrome (NMS) is a rare, life-threatening condition triggered by antipsychotic medications or sudden withdrawal of dopamine agonists, requiring healthcare practitioners’ vigilance and awareness. 
  • The classic triad of NMS symptoms includes fever, muscle rigidity, and altered mental status, with potential complications such as irreversible brain injury, renal failure, and clotting in veins and arteries. 
  • Timely recognition and management of NMS, including withdrawal of neuroleptic medications, temperature reduction, electrolyte rebalance, and other supportive measures, can prevent irreversible damage and save lives.

R.E. Hengsterman


March 21, 2023
Simmons University

As nurses, it is critical to be familiar with rare and life-threatening conditions that may present as diagnostic challenges in clinical settings. One such condition is neuroleptic malignant syndrome (NMS), a potentially fatal reaction to antipsychotic medications or sudden withdrawal of dopamine agonists.

With the rise in off-label use and newer on-label indications for antipsychotics, awareness of NMS becomes even more essential.

This post aims to provide an overview of NMS, its pathophysiology, clinical presentation, differential diagnosis, a case study, and treatment options. By understanding the intricacies of this complex syndrome, you will be better equipped to recognize and manage NMS in patients, potentially preventing irreversible complications and saving lives. 


Neuroleptic Malignant Syndrome risks

An Introduction To Neuroleptic Malignant Syndrome

Idiosyncratic presentations of mental status changes, rigidity, fever, and dysautonomia can arise from potent antipsychotics (neuroleptics) including haloperidol, risperidone, olanzapine, along with metoclopramide, prochlorperazine, promethazine, or the sudden withdrawal of dopamine agonists.

New patients prescribed long-standing antipsychotics are at an increased risk for NMS. Although second-generation antipsychotics, such as olanzapine (Zyprexa) and lurasidone (Latuda) carry a lower overall risk of severe NMS, they have been associated with the syndrome along with atypical antipsychotics, and medications that affect central dopaminergic neurotransmission.

Risks of Neuroleptic Malignant Syndrome

Practitioners should pay particular attention to Haldol and the increasing use among the elderly population to treat delirium, and the use of Haldol in high doses as a prophylactic to reduce incidences of delirium in adult surgical patients. In addition, the elderly population are at risk from the abrupt cessation or reduction of dopaminergic medications such as levodopa which may precipitate NMS. 

The pathologic mechanism of neuroleptic malignant syndrome arises from impaired thermoregulation within the hypothalamus and basal ganglia because of a decrease in dopamine. Patients who experience NMS can suffer irreversible brain injury secondary to hyperthermia and renal failure from myoglobinuria and rhabdomyolysis.

A genetic defect in dopamine receptors may contribute to the disorder as dopamine transfers messages between cells. The blockage of dopamine increases muscle rigidity and within the hypothalamus, contributes to high body temperature and labile blood pressure.

Neuroleptic malignant syndrome might be a neurogenic form of malignant hyperthermia, a genetic disorder triggered by an abnormal reaction to anesthesia. Males are at greater risk for NMS and the pediatric male population, at greater risk for malignant hyperthermia.  

Signs and Symptoms of Neuroleptic Malignant Syndrome

The classic triad of neuroleptic malignant syndrome includes fever, muscle rigidity, and altered mental status (paranoia). Prolonged muscle rigidity can destroy skeletal muscle and prolonged hyperthermia, brain tissue.

Autonomic dysfunction leading to labile blood pressure, incontinence, tachycardia, tachypnea, diaphoresis, tremors, and excessive secretion of saliva (sialorrhea) characterize the scope of neuroleptic malignant syndrome. Other symptoms include liver or kidney failure, hyperkalemia, and clotting in veins and arteries. 

Neuroleptic Malignant Syndrome diagnosis

Differential Diagnosis

For practitioners, the list of potential disorders can include heat stroke, overdose, drug withdrawal, rabies, tetanus, brain abscess, sepsis, encephalitis, malignant catatonia serotonin syndrome, anticholinergic syndrome, lithium toxicity, and meningitis.

The diagnosis of neuroleptic malignant syndrome in a patient includes treatment with neuroleptic drugs within the past 72 hours or the sudden stoppage or reduction of a dopaminergic medication, severe muscle rigidity, fever and altered mental status.

In addition, the patient must have at least two of the following symptoms: diaphoresis, incontinence, trouble swallowing, incontinence, tachycardia, labile blood pressure, leukocytosis, elevated creatine phosphokinase (CPK) and hyporeflexia.  

A Neuroleptic Malignant Syndrome Case Study

A hyperalert 50-year-old professional female with a past psychiatric history of bipolar disorder arrives at your ED with disorganized speech, aggression, paranoid behavior and choreiform movements. The patient is disheveled with cuts and bruises on her torso. She expresses vivid auditory and visual hallucinations to staff. The patient complains of chest pain and shortness of breath.

Per EMS, known drug allergies include haloperidol, chlorpromazine, and fluphenazine. The patient’s home medications include quetiapine, valproic acid, zolpidem, and lithium carbonate. To control the patient’s presenting psychosis, ED staff administered a single 300 mg dose of quetiapine.

Following the antipsychotic administration, the patient became hyperthermic with a fever of 102.7 °F, diaphoretic, tachycardiac (119 beats/minute), tachypneic, blood pressure ranging from (109/82 mm Hg–168/119 mm Hg) and developed extreme muscle rigidity.

Laboratory finding reflected a clinical manifestation of NMS, as the patient’s muscle rigidity contributed to a profound creatine kinase (CK) elevation. 

Neuroleptic Malignant Syndrome Treatment

Treating the complexities of NMS focus on supportive measures in mild cases. These include withdrawal of neuroleptic medications, reduction of body temperature, electrolyte rebalance via IV fluids, and heparin for clot prevention. In severe cases of muscle rigidity, the use of dantrolene can relax skeletal muscle.

To stimulate dopamine production, the dopamine agonist medication bromocriptine, administered every 24 hours until a response or a maximum daily dose of 45 mg/d. In addition, valium to depress the central nervous activity, and electroconvulsive therapy (ECT) to treat the underlying condition. In severe cases patients may require mechanical ventilation.  

After several days, the patient’s symptoms improved. CK level returned to normal, and the physicians taped the bromocriptine dose. Recurrences of NMS can occur. For nurses and other healthcare practitioners’ awareness of the potential for NMS and the vigilance of the presenting clinical features are key.

Neuroleptic Malignant Syndrome treatment

The Bottom Line

As nurses and healthcare practitioners, it is our responsibility to recognize the early signs and symptoms of NMS and initiate prompt intervention to prevent irreversible damage and potentially save lives. Equipped with this knowledge, you can better navigate the complexities of NMS and provide optimal care for patients at risk or suffering from this rare and life-threatening condition.

Remember, vigilance and awareness are key in addressing NMS, and your attentiveness can make all the difference in a patient’s outcome.

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