Serotonin syndrome: symptoms, causes, treatment and how long it lasts

The NHS lists serotonin syndrome among serious sertraline side effects, describing fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated. Patient's article adds that tremor, restlessness (akathisia) and diarrhoea are early features, and that agitation, pressured speech and delirium may follow in more severe cases.

On examination, doctors look for raised blood pressure, fast pulse, high temperature, overactive bowel sounds, wide pupils and sweating. They also look for tremor, inducible or spontaneous clonus (rhythmic muscle jerking), stiff muscles and brisk reflexes. Skin usually looks normal, which helps separate it from some similar conditions.

Patient's article says muscle stiffness, sustained clonus and a temperature that can reach 41 degrees Celsius point to severe disease.

Serotonin is a chemical messenger. NHS information on sertraline describes it as linked to mood, and says SSRI antidepressants increase its level. Serotonin syndrome happens when medicines push serotonin activity too high, producing a combination of neuromuscular, autonomic and mental-state symptoms.

Patient's professional article explains that it can occur through normal therapeutic use, self-poisoning or drug interactions. Most cases involve either two drugs that raise serotonin in different ways or an overdose of one. The illness spans a wide spectrum, from barely noticeable tremor to a life-threatening emergency.

The same article warns that the syndrome is not widely recognised, so mild cases can be overlooked. Continuing or increasing the offending drug can then allow it to progress.

Patient's article says the most important step in all cases is to remove the offending or interacting drugs. Mild cases usually resolve within 24 hours of stopping and may need only supportive care. Drugs with long half-lives, such as fluoxetine, can take longer.

Moderate cases need heart and temperature problems corrected. Supportive measures include intravenous fluids and benzodiazepines to settle agitation. The article mentions cyproheptadine, a serotonin-blocking medicine, but notes there is no definitive evidence of efficacy. Severe cases need intensive care, which may involve sedation, muscle paralysis and ventilation.

It says antipyretics have no role, because the high temperature comes from muscle activity rather than the brain's thermostat. Patients should not stop prescribed medicines abruptly on their own. Take advice from a prescriber, pharmacist or NHS 111 first unless symptoms are severe.

Patient's professional article says mild cases usually resolve within 24 hours of stopping the offending drug, and may need supportive measures only. Drugs with long half-lives or active breakdown products, such as fluoxetine, can mean it takes longer.

It says that if people recover from an acute episode and avoid the provoking agents, the outlook is good, and that most deaths occur within the first 24 hours, which is why severe symptoms need emergency care.

There is no single confirmatory test. Patient's article says the diagnosis is clinical: a doctor links the pattern of features to starting, increasing or combining a serotonergic drug. The Hunter criteria are a set of decision rules developed from overdose cases to confirm moderate or severe toxicity.

Blood tests, such as kidney function and creatine kinase, look for complications like muscle breakdown. Toxicology screens, infection tests and sometimes a head scan or lumbar puncture are used to exclude other causes.

The differential list is long. It includes anticholinergic poisoning, neuroleptic malignant syndrome, malignant hyperthermia, meningitis, encephalitis, withdrawal syndromes and recreational drug toxicity. In the UK, hospital clinicians can get poisoning advice from the Toxbase service.

Using serotonergic drugs is the risk factor. Patient's article says the most commonly implicated are monoamine-oxidase inhibitors (MAOIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and SSRIs, and that the most common causative combinations include an MAOI. The list of drugs it gives is wider than antidepressants.

Patient's article recommends caution when prescribing serotonergic drugs, counselling people starting SSRIs about interactions including over-the-counter and herbal products, and not prescribing an SSRI with an MAOI. Extra care is advised when switching antidepressants or using more than one.

In practice, tell every prescriber and pharmacist about everything you take, including St John's wort, cough remedies and any recreational drugs. Ask before adding a new painkiller or migraine medicine. The BNF lists serotonin syndrome as rare or very rare with SSRIs, and says severe SSRI poisoning can cause it.

Patient's article says that for most people with serotonin-related side effects, sensible changes to medication manage symptoms and prevent toxicity.

The NHS says serotonin syndrome is a rare but serious condition. If you are taking sertraline and you think you are having any serious side effect, call NHS 111, and the NHS says to get help from 111 if you have taken more than your prescribed dose. Call 999 if you think you might be having anaphylaxis, with a swollen throat or tongue, a raised itchy rash and difficulty breathing.

Patient's article advises hospital referral for severe symptoms or after ingestion of an MAOI and an SSRI. A high temperature, stiff muscles, severe agitation or confusion needs emergency care rather than waiting for an appointment. If you are told to go to A&E the NHS says not to drive yourself.

Do not stop a prescribed antidepressant abruptly on your own without advice from a prescriber, pharmacist or NHS 111, unless symptoms are severe.

The article states that if a person recovers from an acute episode and avoids the provoking agents, the outlook is good. It adds that most deaths occur within the first 24 hours, which is why severe symptoms need emergency care.

After recovery, prescribers can try other drugs or restart low doses slowly, while ruling out contributing over-the-counter or illicit substances. Anyone who has had serotonin syndrome should make sure the episode is recorded in their GP notes.

Suspected serotonin syndrome is a medicines-safety problem rather than a long-term condition, so the NHS route is usually urgent: your prescriber, NHS 111 or an emergency department. Patient's article advises hospital referral for severe symptoms, or after ingestion of an MAOI and an SSRI, because the condition can worsen quickly.

A private psychiatrist or GP can review a medication list in a planned way, but anyone with high temperature, severe agitation, stiff muscles or confusion should seek emergency care rather than wait for an appointment.