Tricyclic Antidepressants

Tricyclic Antidepressants is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

  • Multiple TCAs are on the market, including amitriptyline, clomipramine, doxepin, imipramine, trimipramine, desipramine, nortriptyline, and amoxapine.
  • TCAs interact with a wide variety of receptors with many consequent effects in the setting of an overdose. The primary antidepressant effect is due to the inhibition of serotonin and norepinephrine reuptake. Additionally, TCAs modulate the function of central sympathetic and serotonergic receptors, which is thought to contribute to their antidepressant effects.
  • TCAs have antimuscarinic effects, resulting in tachycardia, dry mucous membranes and skin, urinary retention, and decreased GI motility. Patients will also have dilated pupils.1 Sedation is likely due to antihistamine effects. Furthermore, these agents are potent α1-antagonists, leading to the development of hypotension and a reflex tachycardia. Cardiac toxicity is due to sodium channel blockade, resulting in a wide complex rhythm on the ECG.2 TCAs also exhibit a complex interaction with the GABA receptor, which in overdose likely contributes to seizure activity.3

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