What is the recommended dosing for doxepin (Sinequan)?

Doxepin Dosing Recommendations

For most patients with insomnia, doxepin should be initiated at 3-6 mg once daily at bedtime, with a maximum dose of 6 mg for sleep maintenance insomnia. 1, 2

Dosing for Different Indications

Insomnia Treatment

• Initial dose: 3 mg at bedtime 1, 3
• Maximum dose: 6 mg at bedtime 1, 2
• Target population: Particularly effective for sleep maintenance insomnia and early morning awakening 3, 4
• Timing: Administer at bedtime 2

Depression and Anxiety Treatment

• Initial dose: 25-50 mg/day for mild symptoms 2
• Standard dose range: 75-150 mg/day for moderate severity 2
• Maximum dose: Up to 300 mg/day for severe illness 2
• Administration schedule:
  • Can be given as a divided dose or once daily
  • If once daily, maximum recommended dose is 150 mg at bedtime 2
  • The 150 mg capsule strength is intended for maintenance therapy only 2

Cyclic Vomiting Syndrome (CVS)

• Used as a TCA option for prophylactic therapy in moderate-severe CVS 1
• Dosing similar to other TCAs for this indication:
  • Starting dose: 25 mg at bedtime
  • Goal dose: 75-150 mg or 1-1.5 mg/kg at bedtime 1

Special Population Considerations

Elderly Patients

• Start at the lower end of dosing range (3 mg for insomnia, 25 mg for depression) 2, 4
• Elderly patients are more sensitive to anticholinergic effects and sedation 2
• Ultra-low doses (3-6 mg) are particularly well-suited for managing insomnia in older adults 4

Patients with Renal/Hepatic Impairment

• Use lower doses and titrate more slowly 2
• Monitor more closely for adverse effects 2

Titration and Administration

For Insomnia

• Start with 3 mg at bedtime 3, 4
• May increase to 6 mg if needed for sleep maintenance issues 3
• No significant difference in efficacy between 3 mg and 6 mg doses in many patients 4

For Depression/Anxiety

• Start with lower doses (25-75 mg/day) 2
• Increase at appropriate intervals based on individual response 2
• Titrate gradually to minimize side effects 2
• May divide doses or give once daily at bedtime 2

Efficacy Timeline and Monitoring

• Anti-anxiety effects appear before antidepressant effects 2
• Optimal antidepressant effect may take 2-3 weeks 2
• For insomnia, effects on sleep maintenance can be seen after a single dose 3
• Monitor for:
  • Anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention) 2
  • CNS effects (drowsiness, confusion, disorientation) 2
  • Cardiovascular effects (hypotension, hypertension, tachycardia) 2

Common Adverse Effects

• At low doses (3-6 mg): Somnolence and headache, generally comparable to placebo 4, 5
• At higher doses: Anticholinergic effects, sedation, cardiovascular effects 2
• Withdrawal symptoms may occur with abrupt cessation after prolonged use; taper gradually 2

Clinical Pearls

• Low-dose doxepin (3-6 mg) acts primarily as a selective histamine H1 receptor antagonist 5
• Low doses are more effective for sleep maintenance than sleep onset 4, 6
• Higher doses (≥25 mg) engage multiple receptor systems beyond histamine, increasing side effect risk 2, 5
• Doxepin may improve executive function in patients with insomnia more effectively than zolpidem 6
• No evidence of tolerance, rebound insomnia, or discontinuation symptoms with low-dose therapy for up to 3 months 5

When using doxepin for insomnia, the low doses (3-6 mg) provide targeted histamine antagonism without significant engagement of other receptor systems that cause unwanted side effects seen at higher antidepressant doses.