What is the recommended dosing for Doxepin (tricyclic antidepressant) in a patient with insomnia?

Doxepin Dosing for Insomnia

For adults with chronic insomnia, use doxepin 3 mg or 6 mg nightly, taken 30 minutes before bedtime—these are the only evidence-based doses for insomnia treatment, NOT the higher antidepressant doses of 25-300 mg. 1, 2

Evidence-Based Dosing Recommendations

Standard Dosing

• Start with doxepin 3 mg nightly for sleep maintenance insomnia 1, 2
• May increase to 6 mg nightly if 3 mg provides insufficient benefit 1
• Take 30 minutes before bedtime 3
• These low doses work through selective H1-receptor antagonism, NOT tricyclic antidepressant mechanisms 4, 5

Clinical Efficacy Data

At 3-6 mg doses, doxepin demonstrates:

• Wake after sleep onset reduction: 22-23 minutes greater than placebo (95% CI: 14-30 minutes) 1, 2
• Total sleep time improvement: 26-32 minutes longer than placebo (95% CI: 18-40 minutes) 1, 2
• Small-to-moderate improvement in sleep quality 1
• Efficacy evident after single dose on night 1 3, 5
• Sustained benefit for up to 12 weeks without tolerance 5

Critical Dosing Distinctions

Low-Dose (3-6 mg) vs. Higher Doses

The 3-6 mg doses are fundamentally different medications than higher doses: 2

• 3-6 mg: Selective H1-receptor antagonism with minimal anticholinergic effects 4, 5
• 25-300 mg: Broad tricyclic antidepressant effects with significant anticholinergic burden, cardiac risks, and side effects 6, 7

Do NOT use 25-50 mg doses for insomnia—one study using these doses showed increased liver enzymes, leukopenia, thrombopenia, and rebound insomnia 7

Treatment Algorithm Position

When to Use Doxepin

The American Academy of Sleep Medicine recommends doxepin 3-6 mg as a first-line pharmacotherapy option specifically for sleep maintenance insomnia when: 2

• Cognitive Behavioral Therapy for Insomnia (CBT-I) has failed, is unavailable, or patient is unwilling/unable to receive it 2
• Patient has difficulty staying asleep (not primarily sleep onset problems) 1

Comparative Positioning

• Preferred over trazodone, which the American Academy of Sleep Medicine recommends against for insomnia 8
• Comparable efficacy to benzodiazepine receptor agonists but with no DEA scheduling or dependence potential 2
• Superior to zolpidem 5-10 mg for sleep maintenance parameters in head-to-head trials 2

Special Populations

Elderly Patients (≥65 years)

• Use doxepin 3 mg as the starting and often maintenance dose 2
• Minimal fall risk and cognitive impairment compared to benzodiazepines 2
• Safer than long-acting benzodiazepines, which should be avoided completely 2

Patients with Substance Use History

• Doxepin 3-6 mg is appropriate as it has no dependence potential 2
• Not a DEA-scheduled medication 2

Patients with Depression

• Low-dose doxepin (3-6 mg) does NOT treat depression—doses are subtherapeutic for antidepressant effect 9
• One retrospective study showed no improvement in insomnia in depressed patients using low-dose doxepin 9
• If comorbid depression exists, treat depression with full-dose antidepressant and consider adding low-dose doxepin separately for persistent insomnia 8

Safety Profile

Adverse Effects at 3-6 mg

• Somnolence/sedation: Primarily at 6 mg dose, generally at placebo level at 3 mg 2, 5
• Headache: Minimal, near placebo rates 2, 5
• No psychomotor impairment or residual morning sedation in clinical trials 4, 5
• No tolerance, rebound insomnia, or withdrawal symptoms in trials up to 3 months 5

Contraindications and Cautions

While the FDA label lists extensive warnings for higher antidepressant doses 6, at 3-6 mg doses:

• Minimal anticholinergic effects (dry mouth, constipation, urinary retention) 4, 5
• No significant cardiac effects at low doses 5
• Avoid in patients with angle-closure glaucoma 6

Common Pitfalls to Avoid

1. Do NOT prescribe 25 mg, 50 mg, or higher doses for insomnia—these are antidepressant doses with significantly worse side effect profiles 2, 6, 7

2. Do NOT use for sleep onset insomnia as primary indication—doxepin is specifically for sleep maintenance; one pooled analysis showed only a 6.4-minute reduction in sleep latency, which did not reach clinical significance 3

3. Do NOT assume low-dose doxepin will treat comorbid depression—it will not 9

4. Do NOT combine with other sedating medications without caution due to additive effects 8

5. Do NOT use the 150 mg capsule strength for insomnia—this is intended for maintenance antidepressant therapy only 6

Practical Prescribing

• Initial prescription: Doxepin 3 mg tablets, take 1 tablet 30 minutes before bedtime 3
• Titration if needed: Increase to 6 mg after 1-2 weeks if insufficient response 1
• Duration: Can be used for up to 12 weeks with maintained efficacy 5
• Monitoring: Assess sleep maintenance parameters (wake after sleep onset, total sleep time) at 1-2 week follow-up 2