PharmaceuticalHypnoticTricyclic antidepressantH1 antihistamine

Doxepin (low-dose)

Also known as Silenor (low-dose) · Sinequan (antidepressant)

Written by enwyReviewed 5 Aug 20262 sources0 comments

Tricyclic antidepressant used at very low doses (3-6 mg) as a selective histamine H1 antagonist for sleep-maintenance insomnia. Non-scheduled and non-habit-forming, targeting early-morning awakenings with minimal anticholinergic burden at hypnotic doses.

01 Overview

Doxepin is an old tricyclic antidepressant that, at antidepressant doses (75-300 mg), has broad and often troublesome anticholinergic and adrenergic effects. At the very low doses of 3-6 mg (brand Silenor), however, it acts almost purely as a potent selective histamine H1 receptor antagonist and is FDA-approved (2010) specifically for insomnia with difficulty in sleep maintenance.

At these doses it improves wake after sleep onset and sleep efficiency, particularly in the last third of the night, without the dependence, tolerance, or complex sleep behaviours associated with GABAergic hypnotics. It is not a controlled substance. Anticholinergic side effects are minimal at hypnotic doses but become relevant if higher (antidepressant) doses are used off-label for sleep.

02 Mechanism

At 3-6 mg, highly selective antagonism of the histamine H1 receptor suppresses the wake-promoting histaminergic system; higher doses recruit anticholinergic, antiadrenergic, and serotonergic effects.

03 Dosing

Tier	Dose	Route	Notes
Sleep (adult)	3–6 mg/day	Oral	3-6 mg within 30 min of bed; avoid within 3 h of a meal. 3 mg in elderly.

04 Effects

Effect	Magnitude	Evidence
Improved sleep maintenanceDecreases wake after sleep onset and improves sleep in the final hours of the night.	reduced WASO, better late-night sleep	Clinical
No dependence or toleranceNon-scheduled; no meaningful abuse liability or withdrawal at hypnotic doses.		Clinical

05 Side effects

Effect	Severity	Frequency	Evidence	Countermeasures
Residual sedation / somnolenceNext-day drowsiness, driven by the long half-life.	Mild	Common	Clinical
Anticholinergic effects (at higher doses)Dry mouth, constipation, urinary retention, and confusion emerge if antidepressant-range doses are used for sleep.	Moderate	Uncommon at 3-6 mg	Clinical

06 Legal status

United Kingdom

POM

Doxepin is prescription-only. · as of Jan 2026

United States

Rx, non-controlled

Low-dose Silenor FDA-approved 2010; not scheduled. · as of Jan 2026

07 References

Efficacy and safety of doxepin 1 mg, 3 mg, and 6 mg in adults with primary insomniaSleep, 2010

Silenor (doxepin) FDA prescribing informationUS FDA

08 Discussion0 comments

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This page is reference information, not medical advice. Doses and protocols are documented as they appear in the clinical literature and in practice — describing them is not a recommendation to use them. Countermeasures listed here are not a substitute for a physician. Legal status varies by jurisdiction and changes.