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Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.

Serotonin syndrome and anticholinergic toxicity

Psychiatry · UK scope · Sources checked 7 Sept 2026 · Clinical review pending

RapidFull
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Toxic agitation with hyperthermia

Rapidly rising temperature, marked rigidity or clonus, seizures, severe agitation, reduced consciousness or cardiovascular instability can signal life-threatening poisoning.

Action: Stop suspected causative drugs, call senior emergency and critical-care support, assess ABCDE and glucose, begin active supportive treatment and obtain TOXBASE or NPIS advice for the identified and possible co-ingestants.

Synopsis

Differentiate two potentially dangerous drug-induced syndromes through exposure history and examination, stop causative medicines and arrange monitored toxicological treatment with appropriate escalation.

  • Serotonin toxicity combines a serotonergic exposure with neuromuscular, autonomic and mental-state changes, often developing soon after a new drug, dose change or interaction.
  • Clonus and hyperreflexia are important examination clues; severe rigidity can obscure these signs.
  • Antimuscarinic toxicity typically causes delirium with dry skin or mucosae, dilated pupils, urinary retention and reduced bowel activity.
  • Both syndromes can cause tachycardia, hyperthermia and agitation, so pupils or mental state alone do not distinguish them.
  • Reconcile prescribed, over-the-counter and recreational substances, including interactions and mixed overdoses.
  • Stop the relevant drugs and prioritise supportive care, temperature control, monitored treatment of agitation and complication surveillance.
  • Specific antagonists or antidotes require a confirmed clinical indication and toxicology advice; no single antidote is appropriate for every agitated overdose.

Key red flags

Hyperthermia with sustained muscle activity or rigidity requires urgent cooling and airway-capable support; antipyretics alone do not correct the mechanism.

Wide-complex rhythm, syncope, seizure or hypotension after a suspected antimuscarinic overdose raises concern for additional cardiotoxic effects and needs immediate toxicological management.

Investigation priorities

01
Complete exposure timelineFirst step

Identify causative medicines, interacting agents, formulation, dose changes and possible mixed ingestion.

Management branches

Initial recognitionStop exposure and establish severity

Drug history and new neurological or autonomic findings suggest serotonin or antimuscarinic toxicity.

  1. Stop suspect medicines and assess ABCDE, glucose, core temperature, mental state, neuromuscular findings and the ECG.
  2. Identify all plausible exposures and consult the relevant TOXBASE entries, contacting NPIS when the syndrome, ingestion or treatment is uncertain.
  3. Place the patient in a suitable monitored setting and agree observation, investigations and escalation thresholds with the emergency team.

Key medicines

Cyproheptadine for serotonin toxicityNHS Lanarkshire's October 2025 adult guideline gives cyproheptadine 12 mg orally or by nasogastric tube initially, then 8 mg every six hours, with a stated maximum of 32 mg daily. This off-label regional regimen requires toxicology selection; confirm the initial 24-hour schedule including the loading dose, subsequent doses and stop point with NPIS or the treating toxicologist.Evidence for benefit is limited and treatment must be specialist-selected. This enteral medicine must not delay cooling, airway management or control of severe muscle activity. Sedation and antimuscarinic effects matter, especially with uncertain diagnosis or mixed ingestion.
Physostigmine for selected antimuscarinic deliriumUse only a toxicologist-authorised slow intravenous titration with the exact dose, administration rate, repeat interval and stopping criteria prescribed after reviewing the agent, ECG, seizure risk and clinical response. Continuous cardiac monitoring and immediate resuscitation facilities are required.Potential bradyarrhythmia and seizure risk require expert selection; avoid empirical administration where tricyclic or other cardiotoxic co-ingestion, QRS widening or an uncertain mixed syndrome is suspected.
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Sources and review status5 sources · checked 7 Sept 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 7 Sept 2026; clinical approval remains outstanding.

  • NHS Greater Glasgow and Clyde serotonin syndrome guidanceClinical features, differential diagnosis and supportive management.
  • NHS Lanarkshire adult serotonin syndrome guideline October 2025Current regional guidance, review due October 2028; enteral cyproheptadine regimen and maximum with specialist toxicology confirmation.
  • NPIS TOXBASE serviceAgent-specific treatment, antidote selection and mixed poisoning advice.
  • NHS SPS poisoning and toxicity decision resourcesChoosing authoritative UK toxicology information and expert support.
  • University of Utah Poison Control antimuscarinic antidote safetySpecialist poison-centre safety explanation for conduction abnormalities and physostigmine; used for mechanism and precautions, not a UK dosing policy.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom