Serotonin Syndrome: Care Staff Guide to Recognising a Medicines Emergency

Serotonin syndrome is an uncommon but potentially dangerous reaction to medicines that raise serotonin levels in the nervous system. It can begin quickly, within hours of a new medicine or a dose change, and because the early signs such as restlessness, tremor and sweating look like many everyday problems, it is easy to miss. Care staff are often the first to notice that a person has suddenly become agitated, shaky and unwell after a medicines change. This guide, based on NHS Scotland clinical guidance, explains what serotonin syndrome is, which medicines are involved and what to do.

What is serotonin syndrome?

The NHS Scotland Medicines Companion for mental health clinicians describes serotonin syndrome as a spectrum of serotonin toxicity, ranging from mild features to severe, life-threatening toxicity. It says severe toxicity is a medical emergency. It occurs after exposure to a medicine that increases serotonin in the central nervous system. It is usually seen with overdose or interactions between drugs, and occasionally with a single serotonergic medicine in a susceptible person.

Which medicines are involved?

The guidance lists several groups of medicines that can increase serotonin:

• antidepressants, including SSRIs such as fluoxetine and sertraline, SNRIs such as venlafaxine and duloxetine, and tricyclics such as amitriptyline and clomipramine
• St John's Wort, a herbal remedy that many people buy without realising it can interact with prescribed medicines
• opioids, including tramadol, fentanyl and pethidine
• monoamine oxidase inhibitors and related drugs, including phenelzine, moclobemide, linezolid, selegiline and methylene blue
• serotonin-releasing agents, including amphetamines, methylphenidate and ecstasy
• others, including lithium, tryptophan, buspirone and vortioxetine

The most important message for care settings is that the risk usually arises from combinations and changes. Someone who has been stable on an antidepressant for years may be at risk if a new painkiller, antibiotic or herbal remedy is added. This is a core reason for medicines reviews, as explained in our guide to polypharmacy and deprescribing. Lithium also appears on the list, so anyone prescribed it needs particular care with new medicines. Always check with a pharmacist before adding any medicine, supplement or herbal product for someone taking antidepressants.

Symptoms to recognise

The NHS Scotland guidance groups symptoms into three areas:

• Mental state: agitation, anxiety, disorientation, restlessness and excitement
• Neuromuscular signs: tremor, clonus (rhythmic involuntary muscle jerks), overactive reflexes and muscle rigidity
• Autonomic overactivity: high blood pressure, fast heart rate, fast breathing, raised temperature, dilated pupils, heavy sweating, vomiting, diarrhoea and irregular heart rhythm

The guidance states that symptoms usually begin within a few hours of starting a medicine or changing a dose. Diagnosis is clinical, and it requires exposure to a serotonin-raising agent. A mild picture may include restlessness, shivering, sweating and diarrhoea, while severe toxicity includes very high temperature, rigid muscles and a reduced level of consciousness.

Why care staff matter

Staff see people over time and know what is normal for them. A sudden change after a medicines change, particularly in someone who cannot describe their symptoms, may be the only clue. In people with dementia, new agitation and confusion can easily be put down to the dementia, so always ask: has anything changed with their medicines in the last day or two? Use a structured tool such as the 4AT delirium screening tool to document acute changes, then escalate. Do not assume that confusion is delirium alone, but also do not delay medicines checks while exploring other causes.

What to do if you suspect serotonin syndrome

1. Treat it as urgent. If the person has a high temperature, stiff or twitching muscles, severe agitation, very fast heart rate, reduced consciousness or seizures, call 999.
2. Do not give further doses of the suspected medicines until a clinician has advised. Pass the medicines list to the clinician or ambulance crew, including recent changes, over-the-counter products and herbal remedies.
3. Stay with the person, keep them safe and comfortable, and monitor temperature, pulse and breathing. Cool them gently if they are very hot, in line with your service's procedures.
4. Record what you saw, when symptoms started, and what medicines were given and when.
5. Report it as a medicines incident and ask the prescriber or pharmacist to review.

Treatment

The NHS Scotland guidance explains that management involves stopping the serotonergic medicines, assessing severity and providing supportive care. Mild cases usually settle within 24 to 48 hours after the medicine is stopped, although longer-acting agents such as fluoxetine take longer to clear. Moderate to severe cases need acute medical care, which may include support for airway, breathing and circulation, rapid cooling for very high temperature and medicines such as benzodiazepines and cyproheptadine. Once symptoms resolve, a serotonergic medicine may be restarted at a lower dose with close monitoring, or a less serotonergic alternative may be chosen. These are specialist decisions.

How it differs from neuroleptic malignant syndrome

Serotonin syndrome and neuroleptic malignant syndrome share some features, such as fever and rigidity, but the guidance explains important differences. Serotonin syndrome shows neuromuscular excitation, with overactive reflexes and clonus, and tends to appear rapidly after a serotonergic medicine. Neuroleptic malignant syndrome is linked to antipsychotics and typically involves slowed movement, lead-pipe rigidity and a slower onset. Our guide to neuroleptic malignant syndrome explains the second condition. Care staff do not need to tell the two apart. Both are emergencies and both need urgent medical assessment.

Preventing serotonin syndrome

• keep an up-to-date list of every medicine, including as-required, over-the-counter and herbal products
• check with a pharmacist before any new medicine, and report any recent changes at handover
• make sure staff know which of the person's medicines affect serotonin
• be especially careful around dose increases, new prescriptions and overdoses
• never allow medicines to be stopped abruptly without advice, since stopping some antidepressants can cause its own problems, as explained in our guide to safe withdrawal of antidepressants under NICE NG215

Frequently asked questions

How quickly does serotonin syndrome start?

The NHS Scotland guidance says it usually starts within a few hours of starting a medicine or changing the dose.

Is it only caused by antidepressants?

No. Opioids such as tramadol, St John's Wort, lithium, some antibiotics such as linezolid and recreational drugs such as ecstasy can also be involved, especially in combination.

Can a person recover fully?

The guidance says mild cases usually resolve within 24 to 48 hours of stopping the medicine, while severe toxicity needs acute hospital care.

Keep building your knowledge

Medicines safety is everyone's responsibility. Explore the health and social care learning available through Learnsignal CPD to keep your knowledge current.

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.