What is the recommended initial dosage and monitoring plan for a patient starting Doxepin for depression?

Doxepin for Depression: Initial Dosing and Monitoring

For depression, start doxepin at 25 mg at bedtime, then titrate slowly by 10-25 mg increments every 2 weeks to reach a target dose of 75-150 mg daily, with most patients requiring 75-150 mg/day for optimal antidepressant effect. 1

Initial Dosing Strategy

• Begin with 25 mg at bedtime as the standard starting dose 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/day may suffice 1
• In elderly patients, start at the low end of the dosing range (25 mg or less) due to increased risk of confusion, oversedation, and anticholinergic effects 1

Titration Schedule

• Increase by 10-25 mg increments every 2 weeks until reaching the therapeutic target, as slow titration is generally better tolerated 2
• The usual optimum dose range is 75-150 mg/day for most patients with mild to moderate illness 1
• In more severely ill patients, higher doses may be required with subsequent gradual increase to 300 mg/day if necessary, though additional therapeutic effect is rarely obtained by exceeding 300 mg/day 1
• Dose at night to minimize daytime sedation, as drowsiness is the most commonly noticed side effect 1

Dosing Schedule Options

• Total daily dosage may be given on a divided or once-daily schedule 1
• If using once-daily dosing, the maximum recommended dose is 150 mg/day given at bedtime 1
• The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment 1

Critical Monitoring Parameters

Baseline Assessment

• Obtain baseline ECG before initiating therapy, as tricyclic antidepressants can cause QTc prolongation and cardiac dysrhythmias 1
• Assess for contraindications including recent myocardial infarction, cardiac conduction abnormalities, and angle-closure glaucoma 1

Ongoing Monitoring During Titration

• Monitor weekly for the first 2-3 weeks for anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention) 1
• Assess for orthostatic hypotension and cardiovascular effects including tachycardia, particularly in elderly patients 1
• Evaluate for CNS effects including drowsiness, confusion, disorientation, and extrapyramidal symptoms 1
• Watch for emergence of psychotic symptoms or shift to manic symptomatology, which may require dose reduction or addition of an antipsychotic 1

Timeline for Therapeutic Response

• Anti-anxiety effect appears before antidepressant effect 1
• Optimal antidepressant effect may not be evident for 2-3 weeks, so avoid premature dose escalation 1
• Continue monitoring at regular intervals (every 2-4 weeks) during dose titration and stabilization 1

Important Clinical Considerations

Therapeutic Drug Monitoring

• While some sources suggest a therapeutic range of 150-250 ng/mL (parent plus metabolite), 88% of patients in clinical practice have levels below this range with mean concentrations of 89±75 ng/mL at therapeutic doses 3
• A more realistic working range of 50-250 ng/mL is proposed based on reassessment of published data, though there is insufficient evidence for a definitive therapeutic range 3
• Plasma level monitoring should not routinely guide management but may be useful in cases of suspected non-adherence or toxicity 3

Special Populations

• Elderly patients require cautious dosing starting at 25 mg or less, with slower titration due to greater frequency of decreased hepatic, renal, or cardiac function 1
• Sedating effects may cause confusion and oversedation in the elderly, necessitating close observation 1
• In patients with hepatic or renal impairment, start with lower doses and titrate more gradually 1

Common Pitfalls to Avoid

• Never start at high doses (>50 mg) in treatment-naive patients, as this dramatically increases anticholinergic side effects and sedation 1
• Do not expect immediate antidepressant response—allow 2-3 weeks at therapeutic doses before concluding treatment failure 1
• Avoid abrupt discontinuation after prolonged administration; taper gradually over 10-14 days to prevent withdrawal symptoms 1
• Do not confuse drowsiness (which tends to disappear with continued therapy) with treatment failure—this is the most common side effect and typically resolves 1
• Never exceed 300 mg/day, as additional therapeutic effect is rarely obtained and toxicity risk increases substantially 1
• Be aware that if anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention) do not subside with continued therapy or become severe, dose reduction is necessary 1