What is the normal dose of doxepin (tricyclic antidepressant) for treating depression in adults?

Normal Dose of Doxepin for Depression

For treating depression in adults, the standard starting dose of doxepin is 75 mg daily, with a usual therapeutic range of 75-150 mg/day, and doses may be increased up to 300 mg/day in more severely ill patients. 1

Standard Dosing Algorithm

Initial dosing:

• Start with 75 mg/day for patients with mild to moderate depression 1
• For very mild symptomatology or emotional symptoms accompanying organic disease, doses as low as 25-50 mg/day may suffice 1
• In more severely ill patients, higher initial doses may be required with subsequent gradual increase to 300 mg/day if necessary 1

Dose titration:

• The usual optimum therapeutic range is 75-150 mg/day 1
• Additional therapeutic effect is rarely obtained by exceeding 300 mg/day 1
• Dosage may be increased or decreased at appropriate intervals according to individual response 1

Dosing Schedule Options

Once-daily versus divided dosing:

• Total daily dosage may be given on a divided schedule or once daily 1
• If once-daily dosing is employed, the maximum recommended dose is 150 mg/day, which may be given at bedtime 1
• Research supports that once-daily bedtime dosing produces equivalent plasma concentrations and clinical efficacy compared to three-times-daily dosing, though patients may experience more morning sedation with the single bedtime dose 2
• The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment 1

Clinical Evidence for Dosing

Therapeutic plasma concentrations:

• Despite widely cited therapeutic ranges of 150-250 ng/mL (parent plus metabolite), real-world data shows that 88% of patients fall below this range with mean concentrations of 89±75 ng/mL at a mean daily dose of 143±30 mg 3
• A more realistic working range of 50-250 ng/mL has been proposed based on critical reassessment of published data 3
• There is no clear correlation between plasma concentrations and clinical improvement within the commonly cited ranges 3

Comparative dosing studies:

• In controlled trials, mean effective doses ranged from 137.5 mg/day (in comparison with alprazolam) to 25-100 mg/day (in comparison with trazodone) 4, 5
• Both lower doses (25-100 mg once daily) and standard doses (50-225 mg/day) demonstrated antidepressant efficacy in clinical trials 5, 4

Time to Therapeutic Effect

Expected response timeline:

• Anti-anxiety effects appear before antidepressant effects 1
• Optimal antidepressant effect may not be evident for 2-3 weeks 1
• This delayed onset should be considered when evaluating dose adequacy—allow sufficient time at each dose level before escalating

Special Population Considerations

Elderly patients:

• Start at the low end of the dosing range (25-50 mg/day) 1
• Sedating effects may cause confusion and oversedation in elderly patients, requiring close observation 1
• Dose selection should be cautious due to greater frequency of decreased hepatic, renal, or cardiac function 1

Important Clinical Caveats

Critical distinction from low-dose formulations:

• The 3-6 mg doses referenced in sleep medicine guidelines are specifically for insomnia treatment, NOT depression 6, 7
• These ultra-low doses work through selective histamine H1 receptor antagonism and have no antidepressant effect 8
• Do not confuse insomnia dosing (3-6 mg) with antidepressant dosing (75-300 mg)—they are entirely different therapeutic applications 6, 1

Monitoring for adverse effects:

• Most common side effect is drowsiness, which tends to disappear with continued therapy 1
• Anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention) may require dose reduction if severe 1
• Cardiovascular effects including hypotension and tachycardia have been reported occasionally 1