Neuroleptic Malignant Syndrome

Written by Pliro
Mar 12, 2018 Last updated: Apr 1, 2019

What is Neuroleptic Malignant Syndrome?

Neuroleptic Malignant Syndrome or NMS is a rare idiosyncratic neurological reaction caused by antipsychotic drugs. It presents as a neurological emergency in most of the cases. NMS affects 2 out of 10,000 people taking anti-psychotics, and can be fatal if not managed appropriately. Although the condition is quite serious yet once treated properly the patient is expected to have full recovery.

Causes & Risk Factors

NMS is caused by the use of almost all of the antipsychotic drugs. Some of the commonly used antipsychotic drugs leading to Neuroleptic Malignant Syndrome are: Chlorpromazine, Fluphenazine, Haloperidol, Loxapine, Perphenazine, Thioridazine, Risperidone etc.
NMS is more common in men under 40 years of age. The risk factors include:

  • Taking heavy doses of antipsychotic drugs.
  • Quickly increasing the dose of the antipsychotic drug.
  • Quickly switching from one drug to another.
  • Other risk factors include dehydration, iron deficiency, malnutrition, trauma, alcohol etc.


Although the complete pathophysiology leading to this reaction is unknown, yet according to researches, anti-psychotics drugs leading to NMS affects 3 major systems:

  • Sympathetic nervous system: causing to tachypnea, tachycardia, flushing
  • Central Dopamine system: leading to rigidity similar to that seen in patients with Parkinson’s disease.
  • Muscle Member system: causing to hyperthermia (>38C)

Signs and Symptoms

NMS can occur within hours to days after starting the causative anti-psychotic drug. Most of the symptoms appear within 2 weeks of the exposure while all of the symptoms are present after a month. The classic symptom triad of NMS includes “fever, rigidity and altered mental status” yet other symptoms may also be present showing the involvement of aforementioned systems in NMS. Involvement of the sympathetic system leads to flushing, tachycardia (increased heart rate), tachypnea (increases respiratory rate, diaphoresis (excessive sweating) etc.

Muscle rigidity similar to Parkinson’s disease is also a prominent feature of NMS. Moreover seizures, mutism (unable to speak), Dysphagia (unable to swallow), dyspnea (difficulty in breathing) may also be seen. Body temperature (>38C) may also raise leading to hyperthermia.

Once symptoms develop, the disease progresses rapidly within 72hours.Some cases are mild and clear up without any particular management. Others need quick diagnosis and aggressive management for complete recovery. There is an overall 5%-10% mortality rate of NMS.


Diagnosis is made on the basis of both clinical signs and symptoms and biochemical test results. The best test to diagnose in this regard is CPK (creatinine phospho kinase) levels. In most cases there will be a marked elevation of CPK levels. Other than that iron deficiency and metabolic acidosis is also evident in the biochemical studies. Electro encephalogram (EEG) may show non-generalizing slowing.


NMS is considered to be a neurological emergency as a delay in treatment and may lead to permanent morbidity and death. The first and foremost step is to stop the causative agent. This will surely help in further damage and re-occurrences. The management is mostly symptomatic and includes:

  • Heavy hydration especially if there is a spike of CPK levels that may lead to kidney failure.
  • Use of cooling blankets, ice packs and spirit swabs in armpits and groin to treat hyperthermia.
  • Correction of metabolic or biochemical abnormalities e.g. Bicarb infusion etc.
  • Use of medications like Bromocriptine (dopamine agonist) and Dantrolene sodium (muscle relaxant) that sure reduces rigidity.

Previously mortality rate due to NMS was 30% but within the last few years it has dropped to 10% because of the awareness and timely treatment of this rare yet fatal disease. More researches are being made on this untouched disease and it is expected the mortality rate will further reduce with strong and aggressive conservative management only. In order to manage the health issue in a better way it is advised to book an appointment with a neurologist.