Is doxepin (tricyclic antidepressant) effective for treating insomnia?

Doxepin for Insomnia Treatment

Low-dose doxepin (3-6 mg) is effective for treating sleep maintenance insomnia and is recommended when cognitive behavioral therapy for insomnia (CBT-I) is unavailable or insufficient. 1

Efficacy and Indications

Low-dose doxepin has demonstrated significant benefits for sleep maintenance parameters:

• Sleep maintenance improvements:

  • Increases total sleep time by 26-32 minutes compared to placebo 2
  • Reduces wake after sleep onset by 22-23 minutes compared to placebo 2
  • Improves sleep efficiency, particularly in the final third of the night 3

• Specific indication: Doxepin is particularly effective for sleep maintenance insomnia rather than sleep onset difficulties 1, 4

Treatment Algorithm

1. First-line treatment: CBT-I should be considered first-line therapy for chronic insomnia due to superior long-term outcomes and fewer adverse effects 2, 1

2. When to use doxepin:

   • When patients are unable or unwilling to receive CBT-I 2
   • For patients with predominant sleep maintenance difficulties 1
   • As a safer alternative to benzodiazepines, especially in elderly patients or those with substance use history 1

3. Dosing recommendations:

   • Standard adult dose: 3-6 mg 1
   • Elderly patients: Start with 3 mg due to increased sensitivity 1
   • Take once daily before bedtime

Mechanism of Action

At low doses (1-6 mg), doxepin acts as a selective histamine H1 receptor antagonist 5, 4:

• This selective H1 antagonism promotes both initiation and maintenance of sleep 5
• At these low doses, doxepin lacks the significant anticholinergic and antinoradrenergic effects seen with higher antidepressant doses 4

Efficacy Evidence

• Effects are evident after a single administration 5
• Symptom control is maintained for up to 12 weeks 5
• Improves both objective (polysomnographic) and subjective sleep measures 3
• Particularly effective in improving sleep efficiency in the final third of the night 3

Safety Considerations

• Advantages of low-dose doxepin:

  • No significant differences in adverse event rates compared to placebo at low doses 2
  • Sleep architecture is generally preserved 3
  • No significant next-day residual sedation 3
  • No evidence of physical dependence 5

• Important precautions:

  • Suicidal ideation risk is unknown at low doses and cannot be excluded 2
  • Adverse events may increase with longer treatment duration 2
  • Some patients may experience rebound insomnia upon discontinuation 6
  • Use lowest effective dose for shortest possible duration 2

Clinical Pearls

• Low-dose doxepin (3-6 mg) is much lower than doses used for depression (75-150 mg)
• Assess improvement in sleep parameters within 2-4 weeks of starting treatment 1
• Monitor for side effects, particularly daytime sedation, falls, and cognitive changes 1
• Long-term use is generally not recommended; reassess every few weeks until insomnia stabilizes 1
• Consider periodic medication-free intervals to assess continued need 1

Comparison to Other Sleep Medications

The American Academy of Sleep Medicine recommends doxepin as one of several FDA-approved medications for insomnia when CBT-I is insufficient, alongside zolpidem, eszopiclone, temazepam, and suvorexant 1. However, benzodiazepines and trazodone are not recommended for chronic insomnia treatment due to unfavorable risk-benefit profiles 2.