doxepin

Adjunctive therapy • Brands: Sinequan, Silenor

Last reviewed: 2025-12-29

General information

Class: Adjunctive therapy
Common US brands: Sinequan, Silenor
Typical dose range: Depression/anxiety: typical start is 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). Max 300 mg/day inpatient with ECG monitoring.
Therapeutic drug monitoring recommended; reference range 150–250 ng/mL.
Last reviewed: 2025-12-29

Dosing & forms

Forms/strengths: Capsules: 10–150 mg; oral solution 10 mg/mL; low-dose tablets (3 mg, 6 mg) for insomnia.
Frequency: Depression/anxiety: typical start is 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). Max 300 mg/day inpatient with ECG monitoring.
Food: Take on an empty stomach.
Typical range: Depression/anxiety: typical start is 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). Max 300 mg/day inpatient with ECG monitoring.
Therapeutic range: 150–250 ng/mL

Mechanism (brief)

Tricyclic antidepressant; strong antihistamine with serotonin and norepinephrine reuptake inhibition.

Metabolism & Half‑life

Metabolism: CYP2D6, CYP2C19
Half‑life: Single-dose mean 28 h; Steady-state mean 31 h

Therapeutic Drug Monitoring (TDM)

Recommended: Yes

Reference range: 150–250 ng/mL

View labelExact

Monitoring highlights

Sedation, next-day impairment, and falls risk (especially in older adults); driving and occupational safety are often reassessed after dose changes.
Orthostatic vitals during titration and when combined with other hypotensive medications; hydration and slow position changes are commonly emphasized.
Anticholinergic burden (constipation, urinary retention, confusion); bowel regimen planning and avoiding additive anticholinergic polypharmacy are common considerations when feasible.
ECG monitoring for patients with cardiac disease, electrolyte abnormalities, or higher antidepressant doses; repeat ECGs are often considered when adding other QT-active agents.
Therapeutic drug monitoring can be helpful in higher-dose depression regimens, drug interactions (CYP2D6/2C19 inhibitors), unexpected nonresponse, or suspected toxicity.
Mood activation (mania/hypomania) in bipolar-spectrum illness and suicidal thinking during initiation; coordination via the bipolar disorder hub can support planning.

Sources

Doxepin prescribing information — DailyMed (2025)
Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 — Pharmacopsychiatry (2018)
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)
CANMAT 2024 Clinical Guidelines for the Management of Major Depressive Disorder — Canadian Journal of Psychiatry (2024)

General information

Class: Adjunctive therapy

Common US brands: Sinequan, Silenor

Typical dose range: Depression/anxiety: typical start is 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). Max 300 mg/day inpatient with ECG monitoring.

Therapeutic drug monitoring recommended; reference range 150–250 ng/mL.

Last reviewed: 2025-12-29

Dosing & forms

Forms/strengths: Capsules: 10–150 mg; oral solution 10 mg/mL; low-dose tablets (3 mg, 6 mg) for insomnia.

Frequency: Depression/anxiety: typical start is 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). Max 300 mg/day inpatient with ECG monitoring.

Food: Take on an empty stomach.

Typical range: Depression/anxiety: typical start is 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). Max 300 mg/day inpatient with ECG monitoring.

Therapeutic range: 150–250 ng/mL

Monitoring highlights

Sedation, next-day impairment, and falls risk (especially in older adults); driving and occupational safety are often reassessed after dose changes.

Orthostatic vitals during titration and when combined with other hypotensive medications; hydration and slow position changes are commonly emphasized.

Anticholinergic burden (constipation, urinary retention, confusion); bowel regimen planning and avoiding additive anticholinergic polypharmacy are common considerations when feasible.

ECG monitoring for patients with cardiac disease, electrolyte abnormalities, or higher antidepressant doses; repeat ECGs are often considered when adding other QT-active agents.

Therapeutic drug monitoring can be helpful in higher-dose depression regimens, drug interactions (CYP2D6/2C19 inhibitors), unexpected nonresponse, or suspected toxicity.

Mood activation (mania/hypomania) in bipolar-spectrum illness and suicidal thinking during initiation; coordination via the bipolar disorder hub can support planning.