See also:

SSRI Poisoning
SNRI Poisoning
Poisoning – Acute Guidelines for Initial Management
Resuscitation

Key points

1. Be aware of the possibility of serotonin toxicity diagnosis when patients have been exposed to any of the agents implicated
2. Serotonin toxicity encompasses a wide spectrum of clinical signs and symptoms
3. Severe serotonin toxicity is a medical emergency. Untreated, serotonin toxicity can progress to multi-organ failure and death. Severe cases should be managed in a Paediatric ICU

For 24 hour advice, contact the Poisons Information Centre 13 11 26

Background

The term Serotonin Syndrome has been replaced by Serotonin Toxicity to reflect the varied presentation and severity of serotonin poisoning rather than a single clinical entity (syndrome)

• Serotonin toxicity is the clinical manifestation of excessive central and peripheral serotonergic neurotransmission
• It manifests as a wide variety of signs reflecting the triad of CNS, autonomic and neuromuscular dysfunction
• There is a spectrum of severity ranging from mild symptoms to a severe life-threating condition

If serotonin toxicity is suspected please seek senior advice and discuss with toxicologist

Serotonin toxicity can occur in the following clinical settings:

• Drug interaction between two serotonergic agents (most common)
• On introduction or increase in dose of a single serotonergic drug
• Change in therapy from one serotonergic drug to another without adequate washout period
• Interaction between a serotonergic agent and an illicit drug or herbal preparation
• Deliberate self-poisoning with serotonergic agents
• Accidental ingestion of serotonergic agents

Risk assessment

Patients requiring assessment

• Any symptomatic patients
• All patients with deliberate self-poisoning or significant accidental ingestion of serotonergic agents

Patients who have co-ingested a number of serotonergic agents are at significantly greater risk of serotonin toxicity

History and Physical Examination

Diagnosis of serotonin toxicity is based on:

1. A history of ingestion of one or more serotonergic agents
• Clarify the drugs recently prescribed and if any illicit drugs or herbal preparations ingested
• Ascertain the amounts ingested and when the ingestion occurred
2. The presence of characteristic symptoms and physical signs (see table)

Hunter Serotonin Toxicity Criteria

Reference: Austin Clinical Toxicology Service Guidelines: Serotonin (5HT) toxicity

Differential Diagnosis

Serotonin toxicity may mimic other serious conditions which should be considered and excluded such as:

• Neuroleptic malignant syndrome
• Withdrawal syndromes
• Malignant hyperthermia
  • Non-convulsive seizures
• CNS infection

Always check for Medicalert bracelet in any unconscious patient, or any other signs of underlying medical condition (fingerprick marks etc)

Management

Investigations

• 12 lead ECG, blood glucose and paracetamol concentration in deliberate self-poisoning
• Depending on severity further investigations may be necessary to exclude significant complications including urea, creatinine, electrolytes, creatinine kinase, troponin
• Depending on the drug/agent ingested further investigations may be needed (Discuss with toxicologist)  

Treatment

Cease any causative agents
Supportive care and monitoring of temperature, muscle tone and mental status
Serotonin toxicity can be treated with titrated intravenous benzodiazepines in discussion with toxicologist
If symptoms are refractory a serotonin antagonist such as cyproheptadine or chlorpromazine may be considered in discussion with a toxicologist

Cyproheptadine
Oral

<7 years: 2 mg
≥7 years: 4 mg

If continuing treatment for prolonged symptoms use the same dose 3 times a day until symptoms are resolved - usually within 24 hours

Chlorpromazine
Intravenous

Chlorpromazine 0.5 mg/kg (max 25 mg) in sodium chloride 0.9% 10 mL/kg (max 500 mL) IV, over 30 to 60 minutes.
Repeat the dose every 6 to 8 hours until symptoms resolve, provided the patient is not hypotensive

Depending on the drug/agent ingested further treatment may be needed, discuss with toxicologist  

Resuscitation

Standard procedures and supportive care

Consider consultation with local paediatric team when

• Child is symptomatic: requires admission for monitoring and treatment if necessary
• Children at risk of serotonin toxicity with deliberate self-poisoning or significant accidental ingestion should be observed for symptoms for a minimum of 12 hours
• Any child or adolescent presenting with intentional overdose as admission should be considered

Consult Victorian Poisons Information Centre 13 11 26 for advice

Consider transfer when

• Children require care beyond the comfort level of the current hospital  
• Patients who develop severe serotonin toxicity should be managed in PICU

For emergency advice and paediatric or neonatal ICU transfers, see  Retrieval Services.

Consider discharge when

Normal GCS
Normal ECG
Period of observation as above

• Resolution of symptoms with complete recovery can be expected in 24-48 hours

Assessing risk and connecting to community services

• Prior to discharge, adolescents who present with deliberate ingestions need a risk assessment regarding the likelihood of further ingestions or other attempts to self-harm
• Assessment of other drug and alcohol use should also be undertaken
• If, after risk assessment, it is deemed safe to discharge the child or adolescent from hospital, but ongoing mental health or drug and alcohol needs are identified, they should be linked with appropriate services (see links below for services in the State of Victoria)

Discharge information and follow-up:

Parent Information Sheet: Poisoning prevention for children

Poisons Information Centre: phone 13 11 26

Victoria

• Austin Health Toxicology
• Poisons Information Centre
• Child & Adolescent Mental Health Services (CAMHS): Victorian government mental health services are region-based
• Orygen Youth Health: Specialist mental health services for people aged 15 – 25 years, residing in the western and north-western regions of metropolitan Melbourne. Triage/intake - 1800 888 320.
• Headspace: National Youth Mental Health Foundation with local headspace centres
• YSAS (Youth Support and Advocacy Service): Outreach teams across Melbourne and regional Victoria for young people experiencing significant problems with alcohol and/or drug use
• YoDAA: Victoria’s Youth Drug and Alcohol Advice service - provides information and support for youth AOD needs or anyone concerned about a young person
  Infoxchange Service Seeker: Search for local community support services eg local doctor, dentist, counselling services, drug and alcohol services.

Last Updated July 2021