See also

Serotonin syndrome

Resuscitation: hospital management of cardiopulmonary arrest

Resuscitation: care of the seriously unwell child

Key points

1. Deliberate or accidental self-poisoning with Serotonin and Noradrenaline Re-uptake Inhibitors [SNRIs] is potentially life-threatening  
2. Overdoses frequently causes seizures and in large ingestions can cause cardiovascular toxicity   
3. Children who have large ingestions or develop severe serotonin syndrome should be managed in Paediatric ICU  

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

Background 

• Serotonin and Noradrenaline Re-uptake Inhibitors (SNRIs) include atomoxetine, desvenlafaxine, duloxetine, reboxetine and venlafaxine. Desvenlafaxine and venlafaxine are only available as extended-release (ER) preparations
• SNRI poisoning usually causes mild toxicity
• Clinical features are dose-dependent. The toxic dose varies by drug with Venlafaxine having the highest risk of toxicity in overdose:
  • ingestion of >2 g is associated with seizures and serotonergic toxidrome
  • ingestion of >5 g is associated with a 50% risk of seizures
  • ingestion of >8 g is associated with cardiotoxicity
    
• The toxic doses of other SNRIs are not known, however ingestions of less than 800 mg of venlafaxine are unlikely to cause significant toxicity
• Symptoms usually begin within 4 hours of consumption, but may be delayed up to 16 hours (with ER preparations) and usually resolve within 24 hours
• There is a high risk of serotonin syndrome if other serotonergic agents are co-ingested (NB Tramadol and tapentadol have weak SNRI effect)

The risk of seizures following overdose with SNRIs is dose dependent. Seizures may be delayed up to 16 hours following overdose, particularly following overdose with extended release preparations

There is a risk of hypotension, prolonged QRS duration and QT interval, and cardiac dysrhythmias with large ingestions.

Also, there is a high risk of serotonin syndrome if other serotonergic agents are co-ingested.    

Children Requiring Assessment

• All children with deliberate self-poisoning
• Any symptomatic child
• Acute ingestion of unknown quantity
• Children who have ingested doses greater than threshold for assessment (see below)

Dose requiring medical assessment in paediatric accidental ingestions:

*Note these values do not apply to adolescents or adults (please discuss with toxicologist)

Risk Assessment

Red flag features in Red

History

• Intentional overdose or accidental
• Co-ingestants eg paracetamol
• Dose:
  • Stated or likely dose taken
  • If possible, determine the exact name and tablet size
  • Calculate the maximum possible dose per kg

Physical Examination

• May reveal dysphoria, anxiety, mydriasis, tremor, tachycardia and hypertension
• Seizures may be delayed up to 16 hours following overdose, particularly with ingestions of ER preparations 
• Coma or significantly reduced conscious state is not common in SNRI overdose – this suggests co-ingestion or an alternative cause
• Hypotension and cardiac dysrhythmias only occur following large ingestions of Venlafaxine. Atomoxetine can cause QT prolongation
• Evaluate for serotonin syndrome. Hyperthermia is a sign of severe serotonin syndrome which only occurs if there is co-ingestion of other serotonergically active drugs (eg SSRI, MAOIs some TCAs)
• Always check for Medicalert bracelet in any unconscious patient, or any other signs of underlying medical condition (fingerprick marks etc)

Investigations

• ECG on presentation and ECG 6 hourly until discharge
• If large ingestion or prolonged QRS or QTc ongoing cardiac monitoring and 2 hourly ECG is recommended
• blood glucose and paracetamol level in deliberate self-poisoning   

Acute Management

1. Resuscitation

• Standard procedures and supportive care
• Early intubation and ventilation is indicated if large ingestion (Discuss with toxicologist)

2. Decontamination 

• Activated charcoal should only be administered following discussion with toxicologist but should be considered in alert, co-operative patients who have large ingestions
• Whole bowel irrigation may be considered for venlafaxine ingestions >5 g within 4 hours of the estimated ingestion time. Discuss with clinical toxicology

3.  Seizures

• Treat seizures with benzodiazepines
• Avoid phenytoin and fentanyl 

4.  Serotonin Syndrome

• Hyperthermia is a sign of severe serotonin syndrome and should be immediately treated.  Serotonin syndrome can also be treated with titrated intravenous benzodiazepines (Discuss with toxicologist)   

Ongoing care and monitoring

• Because of the risk of seizures, all children with deliberate self-poisoning or accidental ingestion requiring assessment should be observed for a minimum of 16 hours and/or until symptom free
• Children who ingest >5 g of venlafaxine are at increased risk of delayed seizures. Observe them for at least 24 hours after ingestion
• Children with large ingestions, cardiotoxicity or QT-interval prolongation following SNRI poisoning require continuous ECG monitoring and serial 12-lead ECGs for:
  • at least 6 hours after ingestion of an immediate-release preparation
  • at least 16 hours after ingestion of extended-release preparation
  • at least 24 hours after ingestion of >5 g of venlafaxine
• Children with accidental ingestion can be observed at home if asymptomatic and dose is below that requiring medical assessment
  

Consider consultation with local paediatric team when

Admission should be considered for all children and young people with an intentional overdose.

Consult Contact Victorian Poisons Information Centre 13 11 26 for advice

When to consider transfer

Children who have large ingestions or develop severe serotonin syndrome should be managed in a paediatric ICU. 

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

Consider discharge when

• GCS is normal
• ECG is normal
• For most SNRI poisonings, children can be discharged if they remain asymptomatic for:
  • at least 6 hours after ingestion of an immediate-release SNRI preparation
  • at least 16 hours after ingestion of an extended-release SNRI preparation
  • at least 24 hours after ingestion of >5 g of venlafaxine
    

Discharge information and follow-up 

Parent Information: Poisoning prevention for children

Prevention of poisoning (Victorian Poisons Information Centre)

Poisons Information Centre: phone 13 11 26

Victoria

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 e.g. local doctor, dentist, counselling services, drug and alcohol services.

Last updated December 2020