Doxepin
SINEQUAN
What it isTricyclic with very high H1 affinity; at low dose an insomnia agent, at high dose an antidepressant.
Why this oneAt 3 to 6 mg it is essentially a pure H1 antagonist, giving sleep maintenance without anticholinergic or dependence effects.
What limits itAt antidepressant doses it becomes a full tricyclic with all the anticholinergic and overdose liability. The dose determines which drug it is.
FDA-approved for
- depression/anxiety (~1969)
- insomnia (2010)
Off-label
- chronic urticaria
- insomnia
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Insomnia (sleep maintenance) | Adults | 6 mg QHS | 6 mg QHS | 6 mg/day |
| Insomnia (sleep maintenance) | Elderly ≥65 y | 3 mg QHS | 3–6 mg QHS | 6 mg/day |
Renal Undefined
Hepatic Initiate at 3 mg; monitor closely for daytime effects
Instructions
- Take within 30 minutes of bedtime.
- Do not take within 3 hours of a meal.
- Total daily dose should not exceed 6 mg.
Contraindications
- MAOIs (concurrently or within 14 days) due to risk of serious side effects and even death
- Untreated narrow-angle glaucoma or severe urinary retention
Cautions
- Reevaluate if insomnia persists after 7–10 days (possible comorbid disorder)
- Abnormal thinking/behavior, complex sleep behaviors incl. sleep-driving, hallucinations
- Worsening depression/suicidal thinking
- CNS-depressant effects; avoid alcohol and additive CNS depressants
- Not recommended in severe sleep apnea
Adverse reactions
- Somnolence/sedation
- Nausea
- Upper respiratory tract infection
Pregnancy No established increased risk of major birth defects/miscarriage; risk of poor neonatal adaptation with third-trimester TCA exposure
Lactation Doxepin/nordoxepin present in milk; reports of sedation, respiratory depression, poor feeding, hypotonia — breastfeeding not recommended
⚠ BOXED WARNING
- Suicidal thoughts and behaviors in patients under 25
Cost, est. cash$5–$150/month
Generic entry1986
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityTricyclic anticholinergic and cardiac toxicity become life-threatening in overdose.
Active metabolites
Mechanism of action: Doxepin ballicule
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