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# Neuroleptic malignant syndrome

A rare, life-threatening reaction to antipsychotics and other dopamine blockers, with high fever, rigid muscles, confusion and unstable blood pressure.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Hypothalamus](https://durgical.com/en/anatomy/hypothalamus/)
- [Substantia nigra](https://durgical.com/en/anatomy/substantia-nigra/)
- [Caudate nucleus](https://durgical.com/en/anatomy/caudate-nucleus/)
- [Putamen](https://durgical.com/en/anatomy/putamen/)
- [Globus pallidus](https://durgical.com/en/anatomy/globus-pallidus/)

## Why it happens

- [Thermal injury: burns, hyperthermia and hypothermia](https://durgical.com/en/general-pathology/thermal-injury-burns-hyperthermia-and-hypothermia/)
- [Body temperature regulation](https://durgical.com/en/physiology/body-temperature-regulation/)
- [Basal ganglia and movement control](https://durgical.com/en/physiology/basal-ganglia-and-movement-control/)

## What it is

A medical emergency caused by dopamine D2 receptor blockade (or abrupt withdrawal of dopaminergic drugs), defined by the tetrad of hyperthermia, 'lead-pipe' muscle rigidity, altered mental status and autonomic instability. It typically develops over days.

## Who gets it

Rare: estimated in roughly 0.01–0.02% of people treated with antipsychotics today, lower than in the past. Most cases occur in the first two weeks after starting or raising an antipsychotic. Because antipsychotics are widely used in psychiatric and general wards, every clinician and nurse is expected to recognise it.

## Causes

- High-potency first-generation antipsychotics (e.g. haloperidol), also second-generation ones
- Antiemetic dopamine blockers (metoclopramide, prochlorperazine, promethazine)
- Abrupt withdrawal of levodopa or dopamine agonists in Parkinson disease

## Risk factors

- Rapid dose increase, high doses or intramuscular (parenteral) depot or rapid-acting forms
- Dehydration, agitation, exhaustion and hot environment
- Combination with lithium
- Previous episode of NMS
- Organic brain disease, catatonia and iron deficiency

## Pathophysiology

Sudden dopamine blockade in the [hypothalamus](https://durgical.com/en/anatomy/hypothalamus/) disturbs temperature regulation and autonomic control, while blockade in the nigrostriatal pathway ([substantia nigra](https://durgical.com/en/anatomy/substantia-nigra/) to caudate and [putamen](https://durgical.com/en/anatomy/putamen/)) causes severe extrapyramidal rigidity. Sustained muscle contraction generates heat and breaks down muscle (rhabdomyolysis), raising creatine kinase and releasing myoglobin that can injure the kidneys.

## Symptoms and signs

- High fever, often above 38 °C and sometimes above 40 °C
- Generalised 'lead-pipe' rigidity, tremor, dysarthria and dysphagia
- Confusion, agitation, stupor or mutism, often the first sign
- Tachycardia, labile blood pressure, profuse sweating and incontinence
- Slow onset over 1–3 days; reflexes normal or reduced (no clonus)

## Red flags

- Temperature above 40 °C
- Dark urine or falling urine output (myoglobinuria, kidney injury)
- Breathing difficulty or aspiration from rigidity and dysphagia
- Seizures, arrhythmia or coma

## Diagnosis

**Clinical**
Clinical diagnosis in a person exposed to a dopamine antagonist (or withdrawn from a dopamine agonist) within the previous days to weeks who develops fever, rigidity, altered consciousness and autonomic instability, after excluding infection and other causes. International consensus criteria support the diagnosis.

**Tests**
Markedly raised creatine kinase (CK) is typical; leucocytosis, low serum iron, raised transaminases and LDH, electrolyte disturbances, metabolic acidosis, [kidney](https://durgical.com/en/anatomy/kidney/) function and urine myoglobin. Blood cultures and lumbar puncture to exclude infection; toxicology screen.

**Imaging**
Brain CT or MRI to exclude structural causes when the picture is unclear; often normal.

## Differential diagnosis

- Serotonin syndrome (rapid onset, clonus and hyperreflexia, dilated pupils, diarrhoea)
- Malignant hyperthermia (during anaesthesia with volatile agents or succinylcholine)
- Meningitis, encephalitis and sepsis
- Anticholinergic toxicity (dry hot [skin](https://durgical.com/en/anatomy/skin/), no rigidity)
- Heat stroke, malignant catatonia and sympathomimetic intoxication

## Goal of treatment

Stop the causative drug at once, cool the patient and support vital functions to prevent rhabdomyolysis, kidney failure and death; reintroduce antipsychotics only after full recovery and with caution.

## Treatment

**Acute**
Stop all dopamine antagonists (or restart the withdrawn dopaminergic drug); intensive care with intravenous fluids, external cooling, correction of electrolytes and airway protection.

**Medical**
Benzodiazepines for agitation and mild cases; in moderate to severe cases, dantrolene (a muscle relaxant) and/or bromocriptine or amantadine (dopamine agonists).

**Procedure**
Electroconvulsive therapy when the syndrome does not respond to drug treatment or when catatonia persists.

**Follow-up**
Nursing: temperature, vital signs, level of consciousness, fluid balance and urine output, urine colour, serial CK and kidney function; aspiration and pressure-injury prevention.

## Drugs for this condition

- [Bromocriptine](https://durgical.com/en/pharmacology/bromocriptine/)

## Complications

- Rhabdomyolysis and acute kidney injury
- Aspiration pneumonia and respiratory failure
- Disseminated intravascular coagulation and deep vein thrombosis
- Arrhythmias, seizures and death

## Prognosis

With early recognition most patients recover in one to two weeks (longer with depot antipsychotics). Mortality has fallen to roughly 5–10% with modern intensive care. Recurrence is possible when antipsychotics are restarted, so a wait of at least two weeks and a low-potency agent at a low dose are usual.

## Prevention

- Gradual dose increases and avoiding unnecessary parenteral antipsychotics
- Keeping agitated patients hydrated
- Not stopping antiparkinsonian drugs abruptly

## Test yourself

Think of the answer, then tap the question to see it.

## What is the classic tetrad of neuroleptic malignant syndrome?

Hyperthermia, lead-pipe rigidity, altered mental status and autonomic instability.

## Which laboratory finding is typically markedly elevated in NMS?

Creatine kinase (CK), from muscle breakdown.

## How do onset and reflexes distinguish NMS from serotonin syndrome?

NMS develops over days with rigidity and slow or normal reflexes; serotonin syndrome develops within hours with hyperreflexia and clonus.

## Which two specific drugs are used in severe NMS besides supportive care?

Dantrolene (muscle relaxant) and bromocriptine (dopamine agonist).

## Which non-psychiatric drug class can also trigger NMS?

Antiemetic dopamine blockers such as metoclopramide; withdrawal of levodopa can also cause it.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/neuroleptic-malignant-syndrome/)

## Related conditions

- [Serotonin syndrome](https://durgical.com/en/conditions/serotonin-syndrome/)
- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)
- [Acute kidney injury](https://durgical.com/en/conditions/acute-kidney-injury/)
- [Bacterial meningitis](https://durgical.com/en/conditions/bacterial-meningitis/)
- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Neuroleptic Malignant Syndrome](https://rarediseases.org/rare-diseases/neuroleptic-malignant-syndrome/) (National Organization for Rare Disorders (NORD), 2008).

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Source: https://durgical.com/en/conditions/neuroleptic-malignant-syndrome/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/neuroleptic-malignant-syndrome/