Doxepin
Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
Doxepin is a tricyclic antidepressant used at higher doses for depression and anxiety and at very low doses for sleep-maintenance insomnia. Its pharmacology includes norepinephrine and serotonin reuptake inhibition plus strong histamine H1 antagonism, explaining sedation and anticholinergic adverse effects. Antidepressant-dose labeling carries the boxed warning for suicidal thoughts and behaviors in younger patients.
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What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
Doxepin is a tricyclic antidepressant used at higher doses for depression and anxiety and at very low doses for sleep-maintenance insomnia. NutriStack rates the supporting evidence as strong. Common adult dosing is Depression or anxiety: common target 75-150 mg/day orally, with individualized range up to 300 mg/day in selected patients. Insomnia: 3-6 mg orally within 30 minutes of bedtime, not within 3 hours of a meal., though a prescriber sets the actual dose. This profile indexes 3 sources.
The bottom line
Evidence rating strong. Most-documented uses: treatment of major depressive disorder or anxiety at antidepressant doses, treatment of sleep-maintenance insomnia at low doses, reduction in nocturnal awakenings. 3 sources indexed (2013–2025), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
At antidepressant doses, doxepin inhibits norepinephrine and serotonin reuptake and blocks muscarinic, histamine H1, and alpha-1 adrenergic receptors. At low insomnia doses, clinically relevant activity is primarily histamine H1 receptor antagonism, which promotes sleep maintenance. Tricyclic sodium-channel and anticholinergic effects are most concerning at higher doses, in overdose, and in patients with glaucoma, urinary retention, cardiac conduction disease, or interacting sedatives.1,2
Dosing & protocol.
For insomnia dosing, avoid taking within 3 hours of a meal because food can delay absorption and increase next-day effects. Antidepressant doses may be taken with food if needed for tolerability.1,3
Full safety detail.
Side effects
- Sedation
- Somnolence
- Dry mouth
- Constipation
- Blurred vision
- Urinary retention
- Weight gain
- Orthostatic hypotension
- QT prolongation or conduction effects in susceptible patients
- Complex sleep behaviors with hypnotic use
- Activation of mania or hypomania
- Withdrawal symptoms if stopped abruptly
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Reviews & position papers
1- 1Doxepin for insomniaKrystal AD et al. · Sleep Medicine Reviews · 2013
Review summarizes low-dose doxepin efficacy for sleep maintenance and its histamine-mediated mechanism.
Reference material
2- 2DOXEPIN HYDROCHLORIDE capsules, US Prescribing InformationURLU.S. National Library of Medicine · DailyMed · 2025
Labeling describes 75-150 mg/day target dosing, boxed warning, MAOI washout, and tricyclic safety concerns.
- 3DOXEPIN tablets, US Prescribing InformationURLU.S. National Library of Medicine · DailyMed · 2025
Low-dose insomnia labeling specifies 3-6 mg bedtime dosing, food timing, and contraindications including narrow-angle glaucoma and urinary retention.
Common questions.
Quick answers about Doxepin, drawn from the data on this page.
What is Doxepin?
Doxepin is a tricyclic antidepressant used at higher doses for depression and anxiety and at very low doses for sleep-maintenance insomnia. Its pharmacology includes norepinephrine and serotonin reuptake inhibition plus strong histamine H1 antagonism, explaining sedation and anticholinergic adverse effects. Antidepressant-dose labeling carries the boxed warning for suicidal thoughts and behaviors in younger patients.
What is Doxepin used for?
Commonly cited benefits of Doxepin include: Treatment of major depressive disorder or anxiety at antidepressant doses; Treatment of sleep-maintenance insomnia at low doses; Reduction in nocturnal awakenings. NutriStack rates the overall evidence as strong.
What is a typical dose of Doxepin?
A typical adult dose of Doxepin is Depression or anxiety: common target 75-150 mg/day orally, with individualized range up to 300 mg/day in selected patients. Insomnia: 3-6 mg orally within 30 minutes of bedtime, not within 3 hours of a meal.. The commonly recommended form is Oral capsule or solution for depression/anxiety; low-dose tablet for insomnia. These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Doxepin?
Reported side effects include sedation, somnolence, dry mouth, constipation, blurred vision, urinary retention. This is educational information; check with a healthcare professional before use.
How strong is the evidence for Doxepin?
NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
Doxepin in NutriStack.
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