What is the dosage and usage of Doxepin for treating depression, anxiety, and insomnia?

Doxepin Dosage and Usage

For insomnia, use low-dose doxepin 3-6 mg at bedtime specifically for sleep maintenance problems, not sleep onset difficulties. 1 This is the only indication where doxepin has guideline support for insomnia treatment.

Insomnia Treatment

Recommended Dosing

• Low-dose doxepin (3 mg or 6 mg) is recommended specifically for sleep maintenance insomnia (difficulty staying asleep, not falling asleep) 1
• These ultra-low doses work through selective H1 histamine receptor antagonism rather than traditional antidepressant mechanisms 2, 3
• The 3 mg and 6 mg doses showed efficacy in clinical trials without significant anticholinergic or cardiovascular side effects seen at higher antidepressant doses 3

Important Limitations

• Doxepin at these low doses is NOT effective for sleep onset insomnia (trouble falling asleep initially) 1
• The American Academy of Sleep Medicine gives this only a WEAK recommendation, meaning clinical judgment is required 1
• For sleep onset problems, consider alternatives like zaleplon 10 mg, ramelteon 8 mg, or triazolam 0.25 mg instead 1

Positioning in Treatment Algorithm

• Cognitive behavioral therapy for insomnia (CBT-I) should always be first-line treatment 4
• Doxepin is a second-line pharmacologic option specifically for sleep maintenance, alongside suvorexant 4
• For combined sleep onset and maintenance issues, eszopiclone 2-3 mg, zolpidem 10 mg, or temazepam 15 mg are preferred 4

Depression Treatment

Standard Antidepressant Dosing

When used as a tricyclic antidepressant (not for insomnia):

• Starting dose: 75 mg daily 5
• Usual therapeutic range: 75-150 mg daily 5
• Maximum dose: 300 mg daily for severely ill patients 5
• Doses can be divided or given once daily at bedtime (maximum 150 mg for once-daily dosing) 5

Dosing Adjustments

• Mild symptoms or elderly patients: Start with 25-50 mg daily 5
• Increase dosage gradually by increments of the initial dose every 5-7 days until therapeutic benefit or significant side effects occur 1
• Antidepressant effects may take 2-3 weeks to manifest fully, though anti-anxiety effects appear earlier 5

Special Populations

• Elderly patients should start on low doses and be monitored closely for confusion and oversedation 5
• Reduce doses in patients with renal impairment 5

Anxiety Disorders

For anxiety associated with depression or organic disease:

• Use the same antidepressant dosing range (75-150 mg daily) 5
• Do not use low-dose doxepin (3-6 mg) for anxiety disorders—these doses are inadequate for treating psychiatric conditions 4

Critical Safety Considerations

Contraindications

• Absolute contraindications: Glaucoma, urinary retention, hypersensitivity to dibenzoxepines 5
• Avoid in pregnancy and nursing 4
• Use extreme caution with compromised respiratory function, hepatic failure, or heart failure 4

Black Box Warning

• All antidepressants carry increased risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) 5
• Monitor all patients closely for clinical worsening, suicidality, or unusual behavioral changes, especially during initial treatment phases 5
• Doxepin is not approved for pediatric use 5

Common Side Effects at Antidepressant Doses

• Anticholinergic effects: Dry mouth, blurred vision, constipation, urinary retention 5
• Cardiovascular: Hypotension, hypertension, tachycardia 5
• CNS: Drowsiness (most common), confusion, disorientation 5
• At low doses (3-6 mg), side effects are minimal and comparable to placebo 3

Drug Interactions

• At doses above 150 mg daily, doxepin may block the antihypertensive effects of guanethidine 5
• Below 150 mg daily, it can be given concomitantly with guanethidine without blocking antihypertensive effects 5

Key Clinical Pitfalls

Common Mistakes to Avoid

• Do not use low-dose doxepin (3-6 mg) to treat depression—these doses are far below the therapeutic antidepressant range of 75-150 mg 4
• Do not prescribe doxepin for sleep onset insomnia—it only works for sleep maintenance 1
• Do not abruptly discontinue after prolonged use—taper over 10-14 days to avoid withdrawal symptoms 1
• Do not confuse the 150 mg capsule strength as appropriate for treatment initiation—it is for maintenance therapy only 5

Monitoring Requirements

• After 9 months of antidepressant treatment, attempt dosage reduction to reassess need for continued medication 1
• Regular follow-up is essential to assess effectiveness, side effects, and ongoing treatment necessity 4
• Monitor for tolerance, though clinical trials up to 3 months showed no signal for tolerance, rebound insomnia, or discontinuation symptoms at low doses 3