Neuroleptic Malignant Syndrome (NMS): Care Staff Guide to an Antipsychotic Emergency

Neuroleptic malignant syndrome, usually shortened to NMS, is rare, but it is one of the most serious reactions a person taking antipsychotic medicines can have. It can develop over hours to days, and it can look like infection, dehydration, heatstroke or worsening mental illness. Care staff who know the warning signs, and who act quickly, can make the difference between early treatment and a life-threatening emergency. This guide, based on NHS Scotland mental health clinical guidance, explains NMS, who is at risk and what to do.

What is neuroleptic malignant syndrome?

The NHS Scotland guideline describes NMS as a rare, acute and potentially fatal disorder of temperature regulation and movement control. It is caused by blockage of dopamine in the brain following exposure to antipsychotic medicines, and it ranges from mild to a severe medical emergency. Antipsychotics were once called neuroleptics, which is where the name comes from. They are used for psychosis, bipolar disorder and sometimes for distress in dementia, so staff in many settings will support someone who takes them. Our guide to STOMP and antipsychotic medication review in dementia care explains why these medicines need regular review.

Who is at risk?

The guideline distinguishes between stronger and weaker risk factors.

• Stronger risk factors: high-potency first-generation antipsychotics, a recent or rapid increase in dose, taking more than one antipsychotic at once, injections into muscle, abrupt withdrawal of medicines that act on dopamine, and structural brain abnormality.
• Weaker risk factors: older age, existing agitation, male gender, dehydration, other dopamine-blocking medicines such as metoclopramide and lithium, and catatonia.
• Other factors: abrupt withdrawal of anticholinergic medicines, organic brain disease, alcohol use disorder, Parkinson's disease or Wilson's disease, and an overactive thyroid.

Dehydration is the risk factor that care teams can most directly influence. Make sure people on antipsychotics are drinking enough, especially in hot weather or when they are unwell, and report poor intake.

Warning signs

The classic picture, according to the guideline, is a combination of four things:

1. Altered mental state, such as confusion, drowsiness, agitation or reduced responsiveness
2. Fever, with the guideline giving temperatures above 38.5°C as a typical finding
3. Extrapyramidal symptoms, meaning muscle rigidity (stiffness), tremor or other abnormal movement
4. Autonomic instability, including fast heart rate, unstable blood pressure, heavy sweating and fast breathing

Laboratory tests typically show a markedly raised creatine kinase, a marker of muscle damage. The guideline also notes that NMS caused by second-generation antipsychotics may be atypical, with slower or absent fever and rigidity, so staff and clinicians should not rule it out just because the classic signs are missing. A temperature above 40°C or kidney failure caused by muscle breakdown indicates severe NMS and a poorer outlook.

The guideline says NMS generally develops within the first two weeks of starting an antipsychotic or after a dose change, so the days after a new prescription or increase are a time for extra vigilance.

Why it is easy to miss

NMS shares features with other conditions. It can be mistaken for infection, sepsis, heatstroke, catatonia, serotonin syndrome and drug toxicity, and the guideline states it is a diagnosis of exclusion, meaning clinicians must rule out these other causes. This is not a reason to wait. A person with fever, stiffness and confusion needs urgent assessment whatever the eventual diagnosis, and our guide to catatonia explains one of the conditions it can resemble, and sepsis is another. Notably, serotonin syndrome tends to start rapidly after a serotonin-raising medicine and features overactive reflexes and clonus, whereas NMS develops more slowly with slowed movement and rigidity.

What to do if you suspect NMS

1. Treat it as an emergency. If a person on antipsychotics develops fever, stiffness, confusion or an unstable pulse and blood pressure, call 999 or the urgent medical route in your service's procedure, and tell the call handler which medicines the person takes.
2. Do not give the next dose of antipsychotic until a clinician has assessed the person. The first management step in the guideline is to withdraw all potentially causative medicines, which is a decision for the clinician, but staff must not give another dose in the meantime.
3. Monitor temperature, pulse, blood pressure, breathing and level of consciousness, and keep a written record.
4. Encourage or provide fluids if the person is able to drink safely, and cool them if their temperature is very high, following your service's procedures.
5. Hand over the full medicines list, including recent changes, as-required doses and injections, to the clinician or paramedic.
6. Report the incident to your manager and the prescriber.

Hospital treatment

The guideline sets out management that includes withdrawing causative medicines, correcting dehydration and high temperature, monitoring temperature, pulse and blood pressure, and using benzodiazepines for sedation where needed. Blood tests, including white cell count, kidney function, liver function and creatine kinase, are taken. Specialists may treat acute symptoms with medicines such as dantrolene or bromocriptine, and some people need breathing support. Complications can include seizures, abnormal blood clotting, respiratory failure and aspiration pneumonia.

Afterwards: restarting antipsychotics

Recovery needs time, and later decisions about psychiatric treatment are made by senior clinicians. The guideline says the risk of NMS recurring can be as high as 30%. It recommends allowing symptoms to settle completely, waiting at least two weeks, and avoiding the medicine that caused the reaction. If an antipsychotic is restarted, it should be one that is structurally unrelated to the causative agent or has low dopamine affinity, started at a low dose, increased slowly and monitored closely for temperature, blood pressure, pulse, muscle tone and creatine kinase. Depot injections and high-potency first-generation antipsychotics should be avoided. Reintroduction should be started only by senior medical staff.

The guideline also asks that NMS and the medicine that caused it are recorded in the person's notes as an adverse drug reaction. Care staff can help by making sure that this information is on medicines charts, care plans, hospital passports and handover documents, so that it follows the person across services. Our guide to clozapine monitoring is relevant to those who take clozapine, which is among the lower-risk options sometimes used after NMS under specialist supervision.

Reducing the risk

• make sure the person drinks well, especially during illness or heat
• report any new stiffness, tremor, fever or confusion early, particularly after a new antipsychotic or dose increase
• question prescriptions that combine several antipsychotics
• make sure that medicine changes are handed over clearly
• support regular medicines reviews

Frequently asked questions

How common is NMS?

The NHS Scotland guideline describes it as rare. Most people on antipsychotics never develop it, but because it can be fatal, staff should know the signs.

When does it usually happen?

According to the guideline, generally within the first two weeks of starting an antipsychotic or after a dose change, though staff should remain alert at any time.

Is it the same as serotonin syndrome?

No, though some features overlap. The two conditions have different causes and patterns of onset, and both need emergency assessment.

Keep building your knowledge

Recognising rare but serious medicines reactions protects the people in your care. Explore the health and social care learning available through Learnsignal CPD to keep your knowledge up to date.

This article is general information for care staff, based on published NHS and clinical guidance, and does not replace the advice of a person's own prescriber or clinicians. Never stop, start or change a medicine without clinical advice.