What are the guidelines for using Doxepin?

Guidelines for Using Doxepin

Doxepin is indicated for the treatment of psychoneurotic patients with depression and/or anxiety, depression associated with alcoholism, depression associated with organic disease, and psychotic depressive disorders with associated anxiety, with dosing typically starting at lower doses (10-25mg) and titrating up as needed. 1

Indications and Dosing

Depression and Anxiety

• Initial dose: 10-25mg orally at bedtime
• Maintenance dose: 75-150mg daily
• Maximum dose: Up to 300mg daily in severe cases
• Therapeutic plasma concentration range: 130-150 ng/mL 2

Sleep Maintenance Insomnia

• Low-dose doxepin (3-6mg) is effective for sleep maintenance insomnia 3
• Lower doses are particularly effective for elderly patients

Administration Considerations

• Administer as a single dose at bedtime to minimize daytime sedation
• For higher doses (>150mg), consider divided dosing
• Titrate slowly to minimize side effects, particularly in elderly patients
• Steady-state plasma concentrations at 250mg daily: 130±113 ng/mL (parent compound) and 132±94 ng/mL (metabolite) 2

Contraindications

• Hypersensitivity to doxepin or other dibenzoxepines
• Glaucoma
• Urinary retention or tendency toward urinary retention
• Concurrent use with MAO inhibitors 1

Special Populations

Elderly Patients

• Start with lower doses (10-25mg)
• Titrate more slowly
• Monitor closely for anticholinergic side effects and orthostatic hypotension

Renal Impairment

• Reduce dose by 50% in moderate renal impairment (creatinine clearance 10-20 mL/min)
• Avoid in severe renal impairment (creatinine clearance <10 mL/min) 2

Hepatic Impairment

• Use with caution; dose reduction may be necessary
• Monitor plasma levels if available

Pregnancy

• Best to avoid during pregnancy, especially in the first trimester
• No specific teratogenic effects have been demonstrated, but caution is advised 2

Drug Interactions

• Avoid concurrent use with drugs that inhibit hepatic metabolism via cytochrome P450
• Caution with macrolide antibiotics and imidazole antifungals
• Avoid combination with drugs having arrhythmogenic properties (e.g., tricyclic antidepressants) 2
• At doses above 150mg daily, may block the antihypertensive effect of guanethidine and related compounds 1

Side Effects and Monitoring

Common Side Effects

• Dry mouth
• Drowsiness
• Constipation
• Blurred vision
• Orthostatic hypotension (less common than with other tricyclics) 4

Cardiovascular Effects

• Monitor for QT prolongation
• Use with caution in patients with preexisting cardiovascular disease
• Despite common belief, doxepin does not appear to have a better cardiovascular safety profile than other tricyclics in patients with heart disease 5
• ECG monitoring recommended for patients with cardiac disease

Neurological Effects

• Monitor for confusion, ataxia, and seizures, especially with high doses or in patients with reduced drug metabolism 6

Clinical Pearls

• The sedative properties of doxepin make it particularly useful for depressed patients with sleep disturbances 4
• Low-dose doxepin (3-6mg) has selective H1 antagonism and is effective for insomnia with minimal effects on sleep architecture 7
• Consider pharmacogenomic testing for CYP2D6 and CYP2C19 in cases of unexpected toxicity or poor response 6
• In patients with detrusor overactivity, doxepin may help reduce nighttime micturition frequency and incontinence episodes 8

Monitoring Parameters

• Baseline and periodic:
  • Mental status evaluation
  • Blood pressure (sitting and standing)
  • ECG in patients with cardiovascular disease or over 40 years old
  • Liver and renal function tests

Discontinuation

• Taper gradually to avoid withdrawal symptoms
• Monitor for emergence or worsening of depression during discontinuation
• Watch for suicidal ideation, especially in younger patients 1

Doxepin combines antidepressant activity with sedative effects, making it particularly useful for patients with depression accompanied by anxiety or sleep disturbances. While it may cause fewer cardiovascular side effects at therapeutic doses compared to other tricyclics, it still requires careful monitoring, especially in patients with heart disease.