doxepin doxepin doxepin is a medication belonging to the tricyclic antidepressant (tca) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. for hives it is a less preferred alternative to antihistamines. it has a mild to moderate benefit for sleeping problems. it is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus. doxepinclinical datatrade namessinequan, quitaxon, adapin, triadapin, aponal, othersother namesnsc-108160ahfs/drugs.commonographmedlineplusa682390license data us dailymed: doxepin us fda: doxepin pregnancycategory au: c routes ofadministrationby mouth, topical, intravenous, intramuscular injectiondrug classtricyclic antidepressant (tca)atc coded04ax01 (who) n06aa12 (who)legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability13–45% (mean 29%)protein binding76%metabolismhepatic (cyp2d6, cyp2c19)metabolitesnordoxepin, glucuronide conjugateselimination half-lifedoxepin: 8–24 hours (mean 17 hours)nordoxepin: 28–31 hoursexcretionurine: ~50%feces: minoridentifiers iupac name (e/z)-3-(dibenzooxepin-11(6h)-ylidene)-n,n-dimethylpropan-1-amine cas number1668-19-5 y 1229-29-4 (hydrochloride)3607-18-9 (cidoxepin)pubchem cid3158iuphar/bps1225drugbankdb01142 ychemspider3046 yunii5asj6huz7dkeggd07875 yas hcl: d00814 ychebichebi:4710 ychemblchembl1628227 ypdb ligand5eh (pdbe, rcsb pdb)chemical and physical dataformulac19h21nomolar mass279.383 g·mol−13d model (jsmol)interactive image smiles cn(c)cc/c=c1c2=c(c=cc=c2)occ3=c/1c=cc=c3 inchi inchi=1s/c19h21no/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12h,7,13-14h2,1-2h3 ykey:odqwqrrapptvag-uhfffaoysa-n y ny (what is this?) (verify) common side effects include sleepiness, dry mouth, constipation, nausea, and blurry vision. serious side effects may include increased risk of suicide in those under the age of 25, mania, and urinary retention. a withdrawal syndrome may occur if the dose is rapidly decreased. use during pregnancy and breastfeeding is not generally recommended. although how it works for treating depression remains an area of active inquiry, it may involve increasing the levels of norepinephrine, along with blocking histamine, acetylcholine, and serotonin. doxepin was approved for medical use in the united states in 1969. it is available as a generic medication. in 2020, it was the 252nd most commonly prescribed medication in the united states, with more than 1 million prescriptions. medical uses doxepin is used as a pill to treat major depressive disorder, anxiety disorders, and chronic hives, and for short-term help with trouble remaining asleep after going to bed (a form of insomnia). as a cream it is used for short-term treatment of itchiness caused by atopic dermatitis or lichen simplex chronicus. insomnia doxepin is used in the treatment of insomnia. in 2016, the american college of physicians advised that insomnia be treated first by treating comorbid conditions, then with cognitive behavioral therapy and behavioral changes, and then with drugs; doxepin was among those recommended for short-term help maintaining sleep, on the basis of weak evidence. the 2017 american academy of sleep medicine recommendations focused on treatment with drugs were similar. a 2015 agency for healthcare research and quality review of treatments for insomnia had similar findings. a major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found that doxepin had an effect size (standardized mean difference (smd)) against placebo for treatment of insomnia at 4 weeks of 0.30 (95% ci –0.05 to 0.64). the certainty of evidence was rated as very low, and no data were available for longer-term treatment (3 months). for comparison, the other sedating antihistamines assessed, trimipramine and doxylamine, had effect sizes (smd) at 4 weeks of 0.55 (95% ci –0.11 to 1.21) (very low certainty evidence) and 0.47 (95% ci 0.06 to 0.89) (moderate certainty evidence), respectively. benzodiazepines and z-drugs generally showed larger effect sizes (e.g., smds of 0.45 to 0.83) than doxepin, whereas the effect sizes of orexin receptor antagonists, such as suvorexant, were more similar (smds of 0.23 to 0.44). doses of doxepin used for sleep normally range from 3 to 6 mg, but high doses of up to 25 to 50 mg may be used as well. other uses a 2010 review found that topical doxepin is useful to treat itchiness. a 2010 review of treatments for chronic hives found that doxepin had been superseded by better drugs but was still sometimes useful as a second-line treatment. contraindications known contraindications include: hypersensitivities to doxepin, other tcas, or any of the excipients inside the product used glaucoma a predisposition to developing urinary retention such as in benign prostatic hyperplasia use of monoamine oxidase inhibitors in last 14 days pregnancy and lactation its use in pregnant and lactating women is advised against, although the available evidence suggests it is unlikely to cause negative effects on fetal development. the lack of evidence from human studies, however, means it is currently impossible to rule out any risk to the fetus and it is known to cross the placenta. doxepin is secreted in breast milk and neonatal cases of respiratory depression in association with maternal doxepin use have been reported. side effects