NSTK · 01.2026Independent supplement reference
NutriStack
Edition 1.0Updated July 13, 2026

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.

Publication status

Exploratory record, not a reviewed medical publication.

See the editorial and medical-review policies for the publication gate.

This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.

In short

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.

What it's good for
  • Treatment of major depressive disorder or anxiety at antidepressant doses2
  • Treatment of sleep-maintenance insomnia at low doses1,3
  • Reduction in nocturnal awakenings
What to watch for
  • Sedation
  • Somnolence
  • Dry mouth
  • Hypersensitivity to doxepin or other dibenzoxepines1,2
  • Concurrent use with an MAOI, linezolid, or intravenous methylene blue2

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.

The science

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

Class
Tricyclic antidepressant and histamine H1 antagonist
Absorption
Best on an empty stomach
Dosing

Dosing & protocol.

Common range
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.
Recommended form
Oral capsule or solution for depression/anxiety; low-dose tablet for insomnia

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

Safety

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

Contraindications

  • Hypersensitivity to doxepin or other dibenzoxepines1,2
  • Concurrent use with an MAOI, linezolid, or intravenous methylene blue2
  • Untreated narrow-angle glaucoma3
  • Severe urinary retention3
  • Avoid alcohol and other sedative-hypnotics with low-dose doxepin unless supervised
Sources

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
FAQ

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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NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.