Tricyclic Antidepressants (TCAs)

Table of Contents

Clinical Overview

FDA Indications

  • Major Depressive Disorder
  • Obsessive Compulsive Disorder
  • Off Label: Headaches, Neuropathic pain, anxiety, insomnia, Fibromyalgia

How to Dose


  • Amitriptyline or Desipramine: Start at 25mg-50mg QHS and increase by 25mg-50mg per day every 3-5 days (Max dose 300mg/day)
  • Clomipramine: Start at 25mg QHS and increase by 25mg per day every 5-7 days (Max dose 250mg/day)  
  • Nortriptyline: Start at 25mg-50mg QHS and increase by 25mg-50mg per day every 3-5 days (Max dose 150mg/day)


  • Taper by decreasing dose by 25% every 3-5 days. If withdrawal symptoms appear, increase dose and taper more slowly

Side Effects

  • Dry mouth, blurred vision, dizziness, sedation, constipation, weight gain, sexual side effects, urinary hesitancy, sweating
  • Seizures, orthostatic hypotension, arrhythmias, QT prolongation, AV block

Drug Interactions

  • Increased risk of seizures with Tramadol
  • Increase risk of serotonin syndrome with SSRIs, MAOIs and possibly with triptans
  • Bleeding risk with NSAIDs/anticoagulants
  • Avoid using with other highly anticholinergic medications due to risk of anticholinergic delirium, paralytic ileus, and urinary retention
  • Caution in patients with angle-closure glaucoma

Additional Information

  • Elimination Half Life for TCAs: 18-44 hours
  • Metabolized primarily by CYP2D6
  • Also inhibits CYP2D6
  • Food does not affect absorption
  • Imipramine derived from chlorpromazine (Thorazine) and was the first antidepressant approved in the US