In short: serotonin syndrome (also called serotonin toxicity) happens when medicines or substances that raise serotonin build up to excessive levels. Symptoms usually start within hours of starting a new medicine, increasing a dose or combining two serotonin-boosting products. Mild cases settle once the cause is stopped, but severe cases are a medical emergency. If you develop a high temperature, confusion, shaking or muscle jerks after a medicine change, seek medical help straight away.

What is serotonin syndrome?

Serotonin is a chemical messenger that helps regulate mood, sleep, body temperature, muscle activity and digestion. Many common medicines – including antidepressants, some painkillers and some migraine treatments – work by increasing serotonin activity. Taken correctly, most people never have a problem. But if serotonin levels climb too high, usually because two or more serotonin-affecting products are taken together or a dose is raised, the nervous system becomes over-stimulated. This reaction is serotonin syndrome.

It is uncommon, but because it can worsen quickly, it’s worth knowing the warning signs if you take any of the medicines listed below.

Symptoms of serotonin syndrome

Symptoms tend to fall into three groups. You don’t need to have all of them.

Changes in thinking and behaviour

feeling agitated, anxious or restless
confusion or disorientation

Changes in body functions

sweating, shivering or a high temperature
a fast heartbeat or raised blood pressure
diarrhoea, nausea or vomiting
dilated (large) pupils

Changes in muscles and movement

shaking or tremor
muscle twitching or jerking, especially in the legs
overactive reflexes or muscle stiffness

In severe cases there may be a very high temperature (above 38.5°C), seizures (fits), an irregular heartbeat or collapse.

How quickly does it start? Most cases begin within 24 hours of a medicine change, and over half within the first 6 hours. Mild symptoms can be mistaken for flu, anxiety, a stomach bug or antidepressant withdrawal, so tell any clinician you see which medicines you take and what has recently changed.

Which medicines and substances can cause it?

The risk is highest when two or more of these are combined, when a dose is increased, or after taking too much:

SSRI antidepressants – citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
SNRI antidepressants – venlafaxine, duloxetine
Other antidepressants – tricyclics (e.g. amitriptyline, clomipramine), trazodone, mirtazapine, vortioxetine
MAOI antidepressants – phenelzine, tranylcypromine, isocarboxazid, moclobemide. Combining an MAOI with another serotonin-boosting medicine carries the highest risk.
Opioid painkillers – especially tramadol, as well as pethidine, fentanyl, methadone and oxycodone
Migraine medicines – triptans (e.g. sumatriptan); the risk with antidepressants is low but possible
Other medicines – lithium, linezolid (an antibiotic), methylthioninium chloride (methylene blue), ondansetron, and ADHD stimulants such as lisdexamfetamine and dexamfetamine when combined with other serotonergic medicines
Herbal and recreational products – St John’s wort, MDMA (ecstasy), cocaine and amphetamines

Good to know: fluoxetine stays in the body for several weeks after the last dose, so it can still interact with a new medicine for up to around 5 weeks after stopping. Always tell your prescriber if you have recently stopped an antidepressant.

What should I do if I think I have serotonin syndrome?

Severe symptoms – very high temperature, severe confusion, seizures, collapse or a racing, irregular heartbeat: call 999 or go to A&E.
Milder symptoms after a medicine change: contact your prescriber, GP or pharmacist the same day, or call NHS 111.
Don’t take any further doses of the new or increased medicine until you have been assessed, unless a clinician tells you otherwise.
Take your medicines, or a list of them, with you – including any herbal remedies and anything bought over the counter.

How is serotonin syndrome treated?

Treatment depends on severity:

Mild: stopping the medicine responsible is often enough, and symptoms usually settle within about 24 hours.
Moderate: hospital monitoring, fluids, cooling and medicines to calm agitation and muscle overactivity, such as a benzodiazepine (e.g. lorazepam or diazepam).
Severe: intensive care may be needed. An antiserotonin medicine called cyproheptadine is sometimes used.

Once you have recovered, your prescriber will review your medicines before restarting anything. Make sure the episode is recorded in your notes so that future prescribers know about it.

How can I reduce my risk?

Keep an up-to-date list of everything you take, including supplements and herbal remedies.
Check with a pharmacist before buying cold, cough or pain remedies, or St John’s wort, if you take an antidepressant.
Don’t increase your dose or restart an old medicine without advice.
Tell every prescriber – including dentists and hospital teams – about your current and recently stopped medicines.
Avoid recreational drugs, particularly ecstasy (MDMA), cocaine and amphetamines.

Frequently asked questions

How common is serotonin syndrome?

Serious cases are uncommon. Most people taking a single antidepressant at a normal dose never experience it. The risk rises with combinations, dose increases and overdose.

Can I take sertraline with tramadol?

This combination can raise the risk of serotonin syndrome, as well as seizures. It is sometimes prescribed with caution, but you should only take them together if your prescriber knows about both and has advised you to.

Can ADHD medication cause serotonin syndrome?

Stimulants such as lisdexamfetamine, dexamfetamine and methylphenidate have mild serotonergic effects. On their own the risk is very low, but it increases if they are combined with antidepressants or other serotonergic medicines. If you take both, your prescriber should know and you should be aware of the warning signs.

Is serotonin syndrome the same as antidepressant withdrawal?

No. Withdrawal happens after reducing or stopping an antidepressant and causes symptoms such as dizziness, “brain zaps”, low mood and flu-like feelings. Serotonin syndrome happens when serotonin levels are too high, usually after starting, increasing or combining medicines. Both should be discussed with your prescriber.

How long does serotonin syndrome last?

Mild cases usually improve within 24 hours of stopping the cause. It can take longer with medicines that stay in the body for a long time, such as fluoxetine.

Key takeaways

Serotonin syndrome is caused by too much serotonin activity, usually after starting, increasing or combining medicines.
Watch for agitation or confusion, sweating or fever, and shaking or muscle jerks – usually within hours of a change.
Severe symptoms need 999 or A&E; milder symptoms need same-day advice.
Always tell prescribers and pharmacists about every medicine, supplement and herbal product you take.

Sources and further reading

Last reviewed: October 2026 by Shamir Patel, Independent Prescribing Pharmacist, Ready Health. This article is general information and does not replace advice from your own prescriber or pharmacist. In an emergency, call 999.

Worried about your medicines? Ready Health’s pharmacists and clinicians offer private medication reviews and ADHD care in Standish, Wigan.

Serotonin Syndrome: Symptoms, Causes, Medicines Involved and When to Get Help