TCA (Cat. C)

Doxepin 

  • Start with 25mg qHS
  • ↑ by 10-25 mg per week, up to 75-100 mg (higher doses needed for depression)
  • Dosing variation & SE due to patients’ variation in Doxepin metabolism
  • To discontinue 🡪 taper slowly

  • TCA with both antidepressant & antipruritic effect (strong H1 & H2 antihistamine)

  • Antipruritic effects (immediate)
  • ↓ insomnia (immediate) 
  • Antidepressant (takes ~ 2-4 weeks)

  • Narrow angle glaucoma
  • Urinary retention
  • MAOI within last 14 days
  • Caution with comorbidities

  • Sedation (#1), specially in patient with ↓ Doxepin metabolism
  • QT interval prolongation 🡪baseline ECG recommended specially with history of cardiac abnormality
  • ↓ seizure threshold
  • ↑ Weight
  • Anticholinergic SE (urinary retention, dry mouth, blurry vision, constipation, orthostatic hypotension)
  • Psychiatric SE: suicide & manic episode

  • Metabolism via CYP2D6 (can have significant polymorphism. may ↑ or ↓ levels)
  • ↑ toxicity with CYP3A4 inhibitors
  • Any treatment that ↑ QT interval, causes sedation or has anticholinergic SE

  • Amitriptyline (TCA) better for neuropathic pain or itch, same dosage, similar SE profile 

Doxepin discontinuation symptoms 

  • Taper slowly over several weeks, should not be stopped abruptly
  • If stopped abruptly 🡪 nausea, headache, diaphoresis, transient dizziness, insomnia, malaise, & vivid dreams