Serotonin syndrome is a potentially serious medicine reaction caused by too much serotonin activity in the body. Symptoms can include agitation, restlessness, sweating, diarrhoea, shivering, tremor, muscle twitching or stiffness, overactive reflexes, a fast heartbeat, raised body temperature and confusion. Severe cases can cause high fever, seizures, an irregular heartbeat or loss of consciousness. Symptoms often develop within hours of starting a serotonergic medicine, increasing its dose, adding another interacting medicine or taking an overdose. (Mayo Clinic)
Having one of these symptoms does not automatically mean you have serotonin syndrome. Many illnesses and medicine side effects can cause similar symptoms, and there is no single test that confirms the condition. A healthcare professional needs to consider your symptoms, examination findings and everything you have taken. (Mayo Clinic)
Seek urgent medical help if symptoms are severe, rapidly worsening, or include a high fever, seizure, marked muscle rigidity, abnormal heartbeat, fainting or loss of consciousness. Do not wait for an online symptom checker if you are seriously unwell.
For broader information about reactions to psychiatric medicines, see the Mental Health Medication Side Effects hub and our related parent guide.
How serotonin Syndrome Symptoms can be linked to medicines or supplements
Serotonin is a chemical messenger involved in functions including mood, behaviour, digestion and body-temperature regulation. Some medicines increase serotonin signalling. Serotonin syndrome can occur when this effect becomes excessive, particularly when more than one serotonin-related medicine or substance is used together. (Mayo Clinic)
Possible medicine categories
Medicines and substances associated with serotonin syndrome can include:
- SSRIs, such as sertraline, fluoxetine, citalopram and escitalopram.
- SNRIs, including venlafaxine and duloxetine.
- Certain other antidepressants, including some tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs).
- Certain pain medicines, particularly serotonergic opioids such as tramadol; other opioids may also carry interaction warnings when combined with serotonergic medicines.
- Some migraine medicines, including triptans.
- Dextromethorphan, an ingredient found in some cough medicines.
- Linezolid, an antibiotic with monoamine oxidase-inhibiting activity.
- Lithium and some other medicines used in mental healthcare.
- St John’s wort and some other supplements or recreational substances that affect serotonin.
The level of risk is not the same for every medicine or combination. Taking a medicine on this list does not mean that serotonin syndrome will occur. Risk is particularly important when serotonergic medicines are combined or treatment is changed. (Mayo Clinic)
This is one reason your doctor and pharmacist should know about all medicines and products you use, including prescription medicines, pharmacy products, cough and cold remedies, vitamins, herbal preparations and supplements. A product bought without a prescription can still interact with prescribed treatment.
Timing clues
Timing can help a healthcare professional assess whether symptoms may be medicine-related. Serotonin syndrome often begins within minutes to several hours after a relevant medicine exposure. Important changes can include:
- starting a new serotonergic medicine;
- increasing the dose of an existing medicine;
- adding another medicine, supplement or recreational substance;
- changing from one antidepressant or interacting medicine to another; or
- taking more medicine than intended.
Mayo Clinic notes that symptoms usually occur within several hours of starting a new medicine or increasing the dose, while MedlinePlus similarly describes onset within minutes to hours after medicines capable of causing the reaction are taken. (Mayo Clinic)
Tell a healthcare professional about recent medication changes even if they seem unrelated. This can be especially important when different doctors have prescribed different medicines.
For broader guidance on recognising possible medication side effects, use the symptom pattern and timing as information to discuss with a healthcare professional rather than as a way to diagnose yourself.
Medicines and product categories that may be associated with this symptom
Serotonin syndrome usually produces a combination of symptoms rather than one isolated complaint. These may affect your mental state, muscles and reflexes, digestive system, heart rate, blood pressure and temperature.
Possible symptoms include:
- agitation, anxiety or unusual restlessness;
- confusion or other changes in mental state;
- sweating that is not explained by exercise or heat;
- shivering or tremor;
- muscle twitching, jerking or stiffness;
- unusually brisk or overactive reflexes;
- poor coordination;
- dilated pupils;
- diarrhoea, nausea or vomiting;
- a fast heartbeat;
- changing or raised blood pressure; and
- an increased body temperature.
More severe toxicity may cause pronounced muscle rigidity, very high temperature, seizures, abnormal heart rhythm or unconsciousness. (Mayo Clinic)
Is this a common side effect?
Serotonin syndrome is not a routine or expected side effect for most people taking antidepressants or other serotonergic medicines. It is better thought of as a potentially serious adverse drug reaction. Risk tends to rise when serotonergic medicines are combined, a dose is increased or another interacting substance is introduced. (Mayo Clinic)
Symptoms such as sweating, nausea, diarrhoea, anxiety or tremor can also occur for many other reasons. Their presence alone cannot confirm serotonin syndrome.
Red flags: when this symptom may need urgent medical attention
Seek immediate emergency medical care if you or someone with you develops severe or rapidly worsening symptoms such as:
- a high fever;
- a seizure;
- severe muscle stiffness or uncontrolled muscle activity;
- marked confusion or extreme agitation;
- an irregular heartbeat;
- fainting or loss of consciousness; or
- a rapidly deteriorating condition after taking a medicine or combination of medicines.
Severe serotonin syndrome can be life-threatening and requires prompt medical treatment. (Mayo Clinic)
If symptoms are not severe but you suspect serotonin syndrome because they appeared soon after a medication change or interaction, contact a doctor, pharmacist or other healthcare professional urgently for advice.
See our guides to serious medication side effects and when to see a doctor for medication side effects for further safety guidance.
How long can serotonin syndrome last?
The duration varies according to the medicines involved, their doses, how long they remain in the body, the severity of the reaction and the treatment required. With appropriate treatment, symptoms may improve relatively quickly in some cases, but they can last longer when long-acting medicines or significant toxicity are involved. Mayo Clinic notes that milder forms may resolve over a day or two once the causative medicines have been medically managed, while MedlinePlus reports that many treated cases improve within about 24 hours. (Mayo Clinic)
Do not use these timeframes to decide that it is safe to manage suspected serotonin syndrome at home. A healthcare professional should assess concerning symptoms.
What to track before speaking to a doctor or pharmacist
If you are well enough to do so, having accurate information ready can make the medical assessment easier.
Write down:
- every prescription medicine you take;
- over-the-counter and pharmacy medicines;
- cough, cold, pain and migraine products;
- supplements and herbal products;
- recreational substances, if relevant;
- the dose of each product;
- when you last took each medicine;
- any recent dose increases or decreases;
- medicines that were recently started or changed;
- the time the symptoms began;
- whether symptoms are stable or becoming worse; and
- measured temperature, pulse or blood pressure, if you already have a safe way to check these.
Bring the medicine containers, packaging, patient-information leaflets or an up-to-date medication list if you need medical care.
A doctor may need to rule out other causes because infections, medicine overdose, withdrawal, metabolic problems and other serious drug reactions can sometimes produce overlapping symptoms. (MedlinePlus)
What not to do without medical advice
Should I stop the medicine?
Do not independently stop, restart, switch or alter the dose of a prescribed medicine simply because you have read that it can be associated with serotonin syndrome.
If serotonin syndrome is suspected, seek urgent professional medical advice so that a doctor or other appropriate healthcare professional can assess the symptoms and tell you what to do with your medicines. Although management of confirmed serotonin syndrome commonly involves withdrawing the medicine or medicines responsible, that decision should be made in the context of urgent clinical assessment. (MedlinePlus)
You should also avoid:
- doubling or skipping doses to try to correct the problem yourself;
- taking another medicine to treat the symptoms without checking for interactions;
- assuming a pharmacy or herbal product is harmless because it does not require a prescription; or
- deliberately trying the suspected medicine again to see whether symptoms return.
If symptoms are severe or worsening quickly, emergency medical assessment takes priority over trying to work out which medicine is responsible.
Related side-effect guides and reporting options in South Africa
If you suspect that a medicine or health product caused an adverse reaction, you can discuss it with your doctor or pharmacist and may also report side effects in South Africa.
SAHPRA states that members of the public as well as healthcare professionals can report suspected adverse drug reactions. Its Med Safety App is designed for reporting medicine-safety concerns directly to the South African regulator. Reporting a suspected reaction does not require you to prove that the medicine caused it. (Medsafety)
For other symptom-based medicine information, browse the side effect symptoms A-Z.
Medical safety note: This information is for general education and cannot diagnose serotonin syndrome. Because serotonin syndrome can become serious quickly, seek prompt professional medical advice if you develop a concerning combination of symptoms after starting, increasing or combining medicines or supplements. Severe or rapidly worsening symptoms require immediate emergency medical care.