Doxepin

Tricyclic antidepressant (TCA), Antidepressant, Sleep aid (Silenor low-dose), Antihistamine (potent H1)

Doxepin (hydrochloride)

Sinequan (oral antidepressant, US brand discontinued), Silenor (low-dose for insomnia), Prudoxin / Zonalon (topical cream)

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Summary

Classes

Tricyclic antidepressant (TCA), Antidepressant, Sleep aid (Silenor low-dose), Antihistamine (potent H1)

Pharmacy

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)

US FDA Max

300 mg/day (depression, hospitalized); 150 mg/day outpatient; 6 mg/day for insomnia

Pharmacology

Routes

Oral, topical

Onset

Sleep effect from first dose; antidepressant effect over 1-4 weeks

Duration

24 hours (HS dosing)

Half-life

~15 hours (parent); nordoxepin active metabolite ~30 hours

Bioavailability

~30% (oral)

Pregnancy

TCA class signal; limited human data specific to doxepin.^{[citation needed]}

Legal status

Rx-only in US. Carries the antidepressant Boxed Warning for suicidality in children, adolescents, and young adults

Purported mechanism

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).▲0▼ 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.