What is the typical dosing for doxepin (tricyclic antidepressant)?

Doxepin Dosing for Depression

For depression, start doxepin at 75 mg daily and titrate to an optimal range of 75-150 mg daily, with severely ill patients potentially requiring up to 300 mg daily. 1

Standard Dosing Regimen

Initial Dosing

• Start at 75 mg daily for patients with mild to moderate depression 1
• For patients with very mild symptomatology or emotional symptoms accompanying organic disease, doses as low as 25-50 mg daily may suffice 1
• In elderly patients, start at the low end of the dosing range and observe closely for confusion and oversedation 1

Titration and Maintenance

• The optimal dose range is 75-150 mg daily for most patients 1
• More severely ill patients may require higher doses with gradual increase to 300 mg daily if necessary 1
• Additional therapeutic effect is rarely obtained by exceeding 300 mg daily 1
• Dosage may be given on a divided or once-daily schedule 1

Once-Daily Dosing Considerations

• If using once-daily dosing, the maximum recommended dose is 150 mg daily 1
• This dose may be given at bedtime 1
• The 150 mg capsule strength is intended for maintenance therapy only and not recommended for treatment initiation 1

Clinical Response Timeline

• Anti-anxiety effect appears before the antidepressant effect 1
• Optimal antidepressant effect may not be evident for 2-3 weeks 1
• Steady-state concentrations are reached within 2 weeks of beginning doxepin dosing 2

Plasma Concentration Considerations

• Traditional therapeutic ranges of 150-250 ng/mL (parent plus metabolite) are not well-supported by evidence 3
• A preliminary working range of 50-250 ng/mL is more realistic based on actual clinical practice 3
• Mean steady-state serum concentration in clinical practice is approximately 89 ng/mL at mean daily doses of 143 mg 3
• There is strong correlation between total doxepin concentration (doxepin + desmethyldoxepin) and antidepressant effect (r² = 0.76) 2

Pharmacokinetic Properties

• Mean doxepin half-life is 17.7 hours after first dose, rising to 21.8 hours after multiple doses 2
• Mean desmethyldoxepin half-life is 34-37 hours and not significantly affected by multiple dosing 2
• First-pass metabolism is approximately 69.5% 2

Special Populations

Elderly Patients

• Start at low doses due to greater frequency of decreased hepatic, renal, or cardiac function 1
• Sedating effects may cause confusion and oversedation in the elderly 1
• Close observation is required when initiating therapy 1

Patients with Renal Impairment

• Careful dose selection is warranted as elderly patients are more likely to have decreased renal function 1
• The extent of renal excretion has not been fully determined 1

Important Safety Considerations

Common Adverse Effects

• Drowsiness is the most common side effect, which tends to disappear with continued therapy 1
• Anticholinergic effects include dry mouth, blurred vision, constipation, and urinary retention 1
• If adverse effects do not subside or become severe, dosage reduction may be necessary 1

Serious Adverse Effects

• Cardiovascular effects including hypotension, hypertension, and tachycardia have been reported 1
• CNS effects including confusion, disorientation, hallucinations, seizures, and extrapyramidal symptoms may occur 1
• Hematologic effects including bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia have been reported 1

Withdrawal Considerations

• Gradual withdrawal is recommended to avoid withdrawal symptoms after prolonged administration 1
• Withdrawal symptoms are not indicative of addiction 1

Alternative Low-Dose Use for Insomnia

While not the primary focus of this question about depression dosing, doxepin has a distinct low-dose indication:

• For chronic primary insomnia, doxepin 3-6 mg once daily is effective through selective H1 receptor antagonism 4, 5
• This represents a completely different dosing paradigm from antidepressant use 4