Synopsis
Recognise clonus-based serotonin toxicity, reconstruct interacting exposures, stop serotonergic drugs, and control agitation, hyperthermia and organ injury without confusing it with neuroleptic malignant syndrome.
- Serotonin syndrome is a predictable toxicity from excessive serotonergic activity, most often after combination, overdose, dose escalation or a pharmacokinetic interaction rather than an idiosyncratic allergy.
- Symptoms usually begin within hours of a new exposure and combine mental-state change, autonomic activation and neuromuscular hyperactivity.
- Spontaneous, inducible or ocular clonus is the most discriminating bedside sign; hyperreflexia and tremor are often more prominent in the legs.
- Agitation, diaphoresis, mydriasis, tachycardia, hypertension, diarrhoea and increased bowel sounds accompany the motor findings, while severe cases become hyperthermic and acidotic.
- Common contributors include SSRIs or SNRIs with MAO inhibitors, tramadol, linezolid, lithium, dextromethorphan, MDMA, certain opioids and interacting herbal or illicit products.
- A careful timeline must include medicines recently stopped because long half-lives, especially fluoxetine, maintain interaction risk after cessation.
- Hunter criteria use exposure plus clonus, agitation, diaphoresis, tremor, hyperreflexia, hypertonia and temperature, but diagnosis remains clinical and mimics still require assessment.
- Stop serotonergic medicines, reduce stimulation, give intravenous fluids as appropriate, titrate benzodiazepines and use active external cooling; avoid physical struggle.
- Severe temperature is produced by muscle activity rather than a hypothalamic fever set point, so paralysis and ventilation may be life saving whereas antipyretics are ineffective.
- Cyproheptadine is an oral or enteral serotonin antagonist sometimes used for persistent moderate or severe toxicity under toxicology advice; supportive care remains the foundation.
Key red flags
Temperature above 40 degrees, sustained rigidity, seizure, acidosis or rapidly rising CK indicates life-threatening toxicity requiring intubation and paralysis.
Investigation priorities
Identify serotonergic combinations, overdose, long half-life and metabolic interaction.
Management branches
Agitation, sweating and abnormal movements follow a medicine change or overdose.
- Stop all serotonergic and non-essential psychoactive medicines, secure an accurate exposure history and contact the National Poisons Information Service.
- Examine pupils, skin, bowel sounds, reflexes and spontaneous, ocular and inducible clonus while measuring core temperature and cardiorespiratory stability.
- Consider Hunter criteria but investigate infection, NMS, anticholinergic or sympathomimetic toxicity and malignant hyperthermia where discordant findings remain.
Key medicines
Lorazepam or diazepamTitrate intravenous or oral benzodiazepine in small repeated doses using current BNF and toxicology advice, with continuous respiratory observation in severe illness.Respiratory depression, aspiration, delirium and prolonged sedation can occur, especially with co-ingested depressants; airway readiness must match dose escalation.
CyproheptadineToxicology may recommend an initial enteral dose followed by repeat and maintenance doses from current TOXBASE guidance; it cannot be given intravenously.Evidence is limited and anticholinergic sedation and hypotension can complicate assessment; never delay airway control, paralysis or cooling to obtain it.