doxepin

Adjunctive therapy

Brands: Sinequan, Silenor

Last reviewed 2025-12-29

Reviewed by PsychMed Editorial Team.

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Quick answers

What is doxepin?
Doxepin is a tertiary amine tricyclic antidepressant (TCA) with pronounced antihistaminic and anticholinergic properties used for depression, anxiety, and low-dose insomnia adjuncts.
What is Sinequan?
Sinequan is a brand name for doxepin (other brands: Silenor).
What is Sinequan (doxepin) used for?
Label indications include: Depression and anxiety; low-dose formulation approved for insomnia.
What drug class is Sinequan (doxepin)?
Tricyclic antidepressant; strong antihistamine with serotonin and norepinephrine reuptake inhibition.
What strengths does Sinequan (doxepin) come in?
Capsules: 10–150 mg; oral solution 10 mg/mL; low-dose tablets (3 mg, 6 mg) for insomnia.

Snapshot

Class: Adjunctive therapy
Common US brands: Sinequan, Silenor
Therapeutic drug monitoring recommended; reference range 150–250 ng/mL.
Last reviewed: 2025-12-29

Label indications

Depression and anxiety; low-dose formulation approved for insomnia.

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Clinical Highlights

Doxepin is a tertiary amine tricyclic antidepressant (TCA) with pronounced antihistaminic and anticholinergic properties used for depression, anxiety, and low-dose insomnia adjuncts. Potent H1 antagonism drives sedation and weight gain, while anticholinergic effects limit use in older adults and those with glaucoma or urinary retention.

Lower doses (≤6 mg) primarily treat insomnia (Silenor®); higher doses are reserved for resistant depression/anxiety and warrant therapeutic drug monitoring (target combined doxepin + nordoxepin 150–250 ng/mL) to balance efficacy and toxicity.
The compare view and doxepin evidence feed can help contextualize sedation, anticholinergic burden, and cardiac monitoring; the bipolar disorder hub supports mania-prevention planning when treating mood disorders.
Depression/anxiety (FDA 1969)
Insomnia (low-dose tablets) (FDA 2010)
Generic: Capsules and solution available generically; low-dose tablets also generic.

Dosing & Formulations

Capsules: 10–150 mg; oral solution 10 mg/mL; low-dose tablets (3 mg, 6 mg) for insomnia. Depression/anxiety: typical start 25–50 mg at bedtime; titrate by 25–50 mg every 3–4 days to 75–150 mg/day (single HS dose or divided BID). Inpatient maximum 300 mg/day with ECG monitoring.

Insomnia (label): 3–6 mg once nightly on an empty stomach ~30 minutes before bed; label maximum is 6 mg/day, and taking it within 3 hours of a meal can delay absorption.
Lower initial doses (10–25 mg) in elderly, hepatic impairment, or concomitant CYP2D6 inhibitors. Gradual tapering (often ≥4 weeks) is common when discontinuing to reduce cholinergic rebound.

Monitoring & Risks

Boxed warning: Antidepressants increase suicidality in young adults; closer monitoring is common. Sedation: Profound due to H1 antagonism—can cause daytime impairment and increase fall risk.

Anticholinergic effects: Dry mouth, constipation, urinary retention, blurred vision; bowel regimens and hydration can help.
Orthostatic hypotension: Fall precautions are often used, especially in older adults.
Weight gain/increased appetite: Weight, BMI, and metabolic labs are commonly monitored.
QT prolongation and conduction slowing—baseline ECG is often obtained if cardiac history or doses >100 mg/day.

Drug Interactions

Contraindicated with MAOIs; allow a ≥14-day washout is typically used to reduce serotonin syndrome risk. Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine, terbinafine) raise serum levels—dose reductions and toxicity monitoring are often needed.

Enzyme-inducing anticonvulsants (carbamazepine, phenytoin) reduce concentrations—clinical response is monitored and alternatives may be considered.
Additive sedation with alcohol, benzodiazepines, opioids, antihistamines, or other CNS depressants can impair alertness; safety counseling often covers impaired alertness.
Combined anticholinergic burden with low-potency antipsychotics or bladder antimuscarinics increases urinary retention and delirium risk.

Practice Notes

Glaucoma, urinary retention, and constipation risk are commonly screened for; Beers Criteria guidance often informs use in older adults. Baseline ECG and metabolic labs are typically obtained when using higher doses; repeated periodically during long-term therapy.

Counseling covers signs of anticholinergic toxicity and when to seek care for palpitations, syncope, or vision changes.
Coordination with mood-stabiliser teams and the bipolar disorder hub can support mania/hypomania risk mitigation in bipolar-spectrum disorders.
For insomnia dosing, sleep-hygiene counseling is common; taking the dose on an empty stomach can preserve efficacy.

References

Doxepin prescribing information — DailyMed (2025)
Silenor (doxepin) insomnia label — DailyMed (2023)
Roth2011 Doxepin Insomnia
Roth2012 Doxepin Elderly
Maudsley2021 Psych Guidelines
CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)