Tricyclic Antidepressant Poisoning



  • Class of medications sharing a similar tricyclic structure
  • Mechanism of action in therapeutic dosing:
    • Inhibition of serotonin reuptake
    • Inhibition of norepinephrine reuptake
  • Primarily developed as antidepressants
    • Decreased use as antidepressant given alternative medications with safer profiles in overdose
  • Increasingly used for chronic and neuropathic pain
  • Also used for OCD, enuresis, and ADHD


  • Primary mechanism of tricyclic antidepressant (TCA) toxicity:
    • Sodium channel blocking effect (quinidine-like effect)
    • Inhibition of norepinephrine reuptake
    • Peripheral α-blockade
    • Anticholinergic effect
  • TCAs:
    • Amitriptyline
    • Nortriptyline
    • Imipramine
    • Doxepin
  • Newer-generation antidepressants (nontricyclic) have different toxic profile than TCAs:
    • Selective serotonin reuptake inhibitors (SSRIs):
      • Wider margin of safety than TCA
      • Less CNS/cardiovascular toxicity
    • Nonselective serotonin reuptake inhibitors:
      • Serotonin and norepinephrine reuptake inhibitors TCA (SNRIs)
      • Less CNS/cardiovascular toxicity
      • Can cause cardiac dysrhythmias or seizures
      • Venlafaxine (Effexor)
    • See Antidepressants, Poisoning

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