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Tricyclic Antidepressants (TCA’s) are typically prescribed for managing neuropsychiatric disorders and chronic pain. TCA overdose can rapidly deteriorate and can be potentially lethal.

Generic names Brand name
Amitriptyline Endep; Entrip
Clomipramine Anafranil; placil
Dosulepin (dothiepin) Dothep
Doxepin Deptran; Sinequan
Imipramine Tofranil
Nortriptaline Allegron; Nortritabs
 Clinical Presentation


Therapeutically, TCA’s inhibit reuptake of norepinephrine and serotonin in the CNS. In toxicity they exhibit effects at multiple additional receptors including:

In cases of toxicity TCAs block numerous receptors:

  • Cardiotoxicity (QRS prolongation / impaired cardiac contractility) due to sodium channel blockade
  • Seizures due to sodium channel and GABA receptor blockade
  • Vasodilatation / hypotension due to peripheral alpha-adrenergic blockade
  • CNS depression due to histamine blockade
  • Anticholinergic delirium / dry mouth / dry skin / urinary retention due to muscarinic blockade
  • Drowsiness/confusion
  • Tachycardia
  • Slurred speech
  • Hyperreflexia
  • Ataxia
  • Respiratory depression

Mild to moderate overdose

  • Drowsiness/confusion
  • Tachycardia
  • Slurred speech
  • Hyperreflexia
  • Ataxia
  • Respiratory depression

Severe overdose toxicity

  • Coma
  • Respiratory depression
  • Prolonged QRS interval
  • Hypotension
  • Seizures
Anticholinergic effect Cardiotoxicity Neurotoxicity
Agitation Hypotension Sedation/Coma
Dilated pupils Prolonged PR and QRS interval Seizures
Warm, dry, flushed skin Prominent terminal R wave in aVR  
Hyperthermia VT  
Urinary retention   


 Exclusion Criteria
Exclusion Criteria
 Risk Assessment
  • Large overdoses may result in rapid deterioration with coma, seizures and cardiac dysrhythmias
  • Toxicity usually manifests within 2 hours, but any reported overdose requires at least 6 hours of observation
  • >10mg/kg in adults and 5mg/kg in paediatrics is potentially life threatening
  • All TCA overdoses require emergency department review
Primary Care
    Intermediate Care
    • As per Primary Care guidelines
    Advanced Care
    • Cardiac monitoring and 12-lead ECG
    • Establish vascular access
    • Consider obtaining prehospital blood sample
    • Monitor patient persistently, recording full observations every 10 minutes (or 5 minutes if time critical)
    • Manage cardiac dysrhythmia as required
    • Manage seizures as required
    • Consider fluid therapy as required
    • Consider advanced airway management as required
    • Transport Priority 1 if patient time critical, pre-notifying receiving facility
    • in the event of a cardiac arrest, prolonged effective CPR in transit prehospital may still result in a good outcome
    Critical & Extended Care
    • As per Advanced Care guidelines
     Additional Information
    • Prehospital, good supportive care is the mainstay of treatment; particularly focusing on seizure control, optimising ventilation and maintaining circulation. Targeted therapies (eg IV sodium bicarbonate boluses and controlled hyperventilation) are instituted in hospital as indicated
    • Efforts should be made to calculate the ingested dose
    • Patients can deteriorate rapidly and TCA overdoses be fatal, consider peri-arrest if signs of instability. Cardiac arrest following a seizure is not uncommon in large overdoses
    • Significant risk of arrhythmias - It is unlikely that defibrillation will be effective
    • Urgent transport to hospital, where advanced treatments can be provided as indicated
    Key Terms & Links
    Extended Care:
    Colour assist:


    B. P, Tricyclic Antidepressant Toxicity [Online]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK430931/ (Accessed: 1 May 2023).

    R. Buttner, (2020). Pharm 101: Tricyclic Antidepressants [Online]. Available at: https://litfl.com/pharm-101-tricyclic-antidepressants/ (Accessed: 2 May 2023).

    E. Burns, (2018). Tricyclic Overdose [Online]. Available at: https://litfl.com/tricyclic-overdose-sodium-channel-blocker-toxicity/ (Accessed: 2 May 2023).

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    Head of Clinical Services


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