Doxepin: Difference between revisions
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{{MedTemplate | {{MedTemplate | ||
| generic | | generic = Doxepin (hydrochloride) | ||
| brand | | brand = Sinequan (oral antidepressant, US brand discontinued), Silenor (low-dose for insomnia), Prudoxin / Zonalon (topical cream) | ||
| structure | | structure = | ||
| classes | | classes = [[:Category:Tricyclic antidepressants|Tricyclic antidepressant (TCA)]], [[:Category:Antidepressants|Antidepressant]], [[:Category:Sleep aids|Sleep aid (Silenor low-dose)]], [[:Category:Antihistamines|Antihistamine (potent H1)]] | ||
| | | uses = <vote slug="major-depressive-disorder-use">Major depressive disorder (FDA, oral antidepressant dose)</vote>, <vote slug="anxiety-doxepin-use">Anxiety disorders (FDA)</vote>, <vote slug="insomnia-sleep-maintenance-use">Insomnia, sleep maintenance type (Silenor 3-6 mg, FDA)</vote>, <vote slug="chronic-urticaria-pruritus-use">Chronic urticaria and pruritus (off-label, leveraging H1 antihistamine activity)</vote>, <vote slug="topical-pruritus-use">Topical treatment of localized pruritus (Prudoxin 5% cream, FDA)</vote> | ||
| | | starting_dose = Depression: 25-75 mg/day to start, titrate to 75-150 mg/day at bedtime. Insomnia (Silenor): 3 mg PO 30 minutes before bedtime, max 6 mg. Topical (Prudoxin): apply to affected area every 3-4 hours | ||
| | | preparations = Capsules 10, 25, 50, 75, 100, 150 mg; oral concentrate 10 mg/mL; Silenor tablets 3, 6 mg; topical cream 5% (Prudoxin, Zonalon) | ||
| | | fda_max = 300 mg/day (depression, hospitalized); 150 mg/day outpatient; 6 mg/day for insomnia | ||
| | | pill_id = | ||
| routes | | routes = Oral, topical | ||
| onset | | onset = Sleep effect from first dose; antidepressant effect over 1-4 weeks | ||
| duration | | duration = 24 hours (HS dosing) | ||
| halflife | | halflife = ~15 hours (parent); nordoxepin active metabolite ~30 hours<ref name="silenor-label">FDA Prescribing Information, Silenor (doxepin tablets), Pernix/Currax, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022036lbl.pdf</ref> | ||
| bioavailability = ~30% (oral)<ref name="silenor-label" /> | |||
| pregnancy = TCA class signal; limited human data specific to doxepin.{{citation needed}} | |||
| legal = [[USLegal:Prescription only|Rx-only]] in US. Carries the antidepressant '''Boxed Warning''' for suicidality in children, adolescents, and young adults<ref name="silenor-label" /> | |||
| | | mechanism = <vote slug="doxepin-mech-claim">Tricyclic antidepressant with the '''strongest H1 antihistamine activity of any TCA''', actually the most potent H1 antihistamine in clinical use, exceeding diphenhydramine on a molar basis. This is why '''low-dose doxepin (Silenor 3-6 mg) is uniquely sedating without anticholinergic burden''' at low doses: the H1 effect saturates at very low concentrations, while the muscarinic and α-adrenergic effects do not contribute meaningfully until higher antidepressant doses (75-300 mg).</vote> At antidepressant doses, the standard TCA mechanisms apply: serotonin and norepinephrine reuptake inhibition, anticholinergic, antihistaminergic, and α1-adrenergic antagonism. CYP2D6 and CYP2C19 substrate; CPIC TCA dosing guidance applies<ref name="cpic-tca">CPIC Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants, 2016. https://cpicpgx.org/guidelines/guideline-for-tricyclic-antidepressants-and-cyp2d6-and-cyp2c19/</ref>. | ||
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== References == | |||
<references /> | |||
[[Category:Tricyclic antidepressants]] | |||
[[Category:Antidepressants]] | [[Category:Antidepressants]] | ||
[[Category:Sleep aids]] | |||
[[Category:Antihistamines]] | |||