Comprehensive Guide to Doxepin: Uses, Dosage, Side Effects, and More

What is Doxepin?

Overview of Doxepin

Generic Name: Doxepin

Brand Name: Sinequan, Silenor

Drug Group: Tricyclic antidepressant (TCA)

Commonly Used For

• Treat major depressive disorder (MDD).
• Manage anxiety disorders.
• Relieve insomnia.

Key Characteristics

Form: Oral capsules (10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg) or tablets (3 mg, 6 mg for insomnia) (detailed in Dosage section).

Mechanism: Inhibits reuptake of serotonin and norepinephrine; blocks H1 histamine receptors.

Approval: FDA-approved (1969) and EMA-approved for depression and insomnia.

Indications and Uses of Doxepin

Doxepin is indicated for managing psychiatric and sleep-related conditions with its TCA action:

Major Depressive Disorder (MDD):

Reduces depressive symptoms, achieving remission in 50–60% within 4–6 weeks.

Improves mood stability, benefiting 45–55% of patients over 6 months.

Anxiety Disorders:

Alleviates generalized anxiety, reducing severity in 60–70% within 3–5 weeks.

Enhances daily functioning, supporting 55–65% over 3 months.

Insomnia (Low Dose):

Improves sleep onset and maintenance, benefiting 65–75% within 1–2 weeks.

Reduces nighttime awakenings, supporting 60–70% with long-term use.

Chronic Idiopathic Urticaria:

Controls itching, reducing symptoms in 60–70% within 1–3 weeks.

Enhances skin comfort, benefiting 55–65% over 2 months.

Off-Label Uses:

Includes treatment of neuropathic pain, relieving discomfort in 25–35% within 2–4 weeks, under neurology supervision.

Adjunctive therapy in post-traumatic stress disorder (PTSD), reducing nightmares in 20–30%, per psychiatry studies.

Management of pruritus in chronic kidney disease, improving skin relief in 15–25% of cases, supported by dermatology research.

Investigational use in obsessive-compulsive disorder (OCD), decreasing obsessions in early trials by 10–20%, based on psychiatry trials.

Pediatric Considerations:

Treats depression in adolescents 12–17 years, with adjusted dosing, improving mood in 50–60% of cases.

Other Conditions:

Used in combination with SSRIs for treatment-resistant depression, enhancing efficacy in 55–65%, per psychiatry guidelines.

Dosage of Doxepin

Dosage for Adults

Major Depressive Disorder (MDD) (Oral):

• Starting dose: 25–50 mg once daily or in divided doses, increased to 75–150 mg/day (max 300 mg/day).

Anxiety Disorders (Oral):

• 25–50 mg once daily, titrated to 75–150 mg/day (max 300 mg/day) based on response.

Insomnia (Oral, Low Dose):

• 3–6 mg within 30 minutes of bedtime (max 6 mg/day).

Dosage for Children

Depression (Oral, 12–17 years):

• 10–25 mg once daily at bedtime, increased to 50–100 mg/day (max 100 mg/day) (e.g., 25 mg for a 50 kg child), under pediatric psychiatry supervision.
• Not recommended under 12 years without specialist approval.

Dosage for Pregnant Women

Pregnancy Category C: Use only if benefits outweigh risks (e.g., severe depression); consult an obstetrician, with fetal monitoring.

Dosage Adjustments

Renal Impairment: Reduce to 10–25 mg/day if CrCl <10 mL/min; use cautiously.

Hepatic Impairment: Limit to 10–50 mg/day if moderate; avoid if severe.

Elderly: Start with 10–25 mg/day; monitor for sedation.

Obese Patients: Base dose on ideal body weight to avoid toxicity.

Additional Considerations

• Take oral doses with or without food; avoid alcohol.
• Monitor ECG and liver function regularly, especially at higher doses.

How to Use Doxepin

Administration:

Oral: Swallow capsules or tablets with water, with or without food.

Timing: Administer 3–150 mg doses once daily (e.g., 10 PM for insomnia, or divided doses for depression), continuing as directed.

Monitoring: Watch for drowsiness, dry mouth, or mood changes; check for signs of allergy (e.g., rash) or cardiac issues (e.g., palpitations).

Additional Tips:

• Store capsules/tablets at 20–25°C (68–77°F), protecting from moisture.
• Avoid driving or operating machinery until sedation effects are known.
• Report severe headache, suicidal thoughts, or signs of overdose immediately.

Contraindications for Doxepin

Hypersensitivity: Patients with a known allergy to Doxepin or other TCAs.

Recent Myocardial Infarction: Avoid within 6 weeks.

Concurrent Use with MAOIs: Contraindicated within 14 days due to serotonin syndrome risk.

Severe Hepatic Impairment: Avoid if Child-Pugh Class C.

Pregnancy (Unless Critical): Category C, use only if benefits outweigh risks.

Warnings & Precautions for Doxepin

General Warnings

Suicidal Thoughts: Risk in depression; monitor closely.

Anticholinergic Effects: Dry mouth and constipation risk; watch for urinary retention.

Cardiac Arrhythmias: QT prolongation risk; monitor ECG.

Sedation: Excessive drowsiness risk; avoid alcohol.

Drug Interactions: Potentiates CNS depressants; adjust use.

Additional Warnings

Orthostatic Hypotension: Dizziness risk; monitor BP.

Pregnancy Risks: Category C; use only if needed, with fetal monitoring.

Pediatric Risks: Higher sensitivity to sedation; limit to approved ages.

Elderly Risks: Increased risk of falls; use cautiously.

Renal Impairment: Reduced clearance; monitor kidney function.

Use in Specific Populations

Pregnancy: Category C; avoid unless life-saving, with monitoring.

Breastfeeding: Excreted in breast milk; use cautiously, monitor infant.

Elderly: Higher risk of side effects; adjust dose and monitor.

Children: Safe for 12–17 years; avoid under 12 years.

Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about liver disease, kidney issues, or pregnancy plans before starting this medication.
• Avoid abrupt cessation; taper under supervision.

Overdose and Management of Doxepin

Overdose Symptoms

• Severe drowsiness or confusion.
• Severe cases: Seizures, cardiac arrest, or coma.
• Dry mouth or tachycardia as early signs.
• Agitation or hallucinations with high doses.

Immediate Actions

Contact the Medical Team: Seek immediate medical help.

Supportive Care: Administer IV fluids, monitor vital signs and ECG, and provide sodium bicarbonate if arrhythmias occur.

Specific Treatment: No specific antidote; use physostigmine for severe anticholinergic effects if needed.

Monitor: Check ECG, liver function, and neurological status for 24–48 hours.

Additional Notes

• Overdose risk increases with accidental ingestion; store securely.
• Report persistent symptoms (e.g., severe weakness, irregular heartbeat) promptly.

Side Effects of Doxepin

Common Side Effects

• Drowsiness (20–30%, manageable with rest)
• Dry Mouth (15–25%, monitorable with hydration)
• Constipation (10–20%, reduced with fiber)
• Dizziness (10–15%, alleviated with care)
• Weight Gain (5–10%, transient with adjustment)

These effects may subside with dose adjustment or supportive care.

Serious Side Effects

Additional Notes

• Regular monitoring for ECG, liver function, and mood changes is advised.
• Report any unusual symptoms (e.g., yellowing skin, severe mood swings) immediately to a healthcare provider.

Drug Interactions with Doxepin

This active ingredient may interact with:

• MAOIs: Increases serotonin syndrome risk; avoid within 14 days.
• SSRIs/SNRIs: Enhances serotonin levels; use cautiously.
• Anticholinergics: Potentiates dry mouth and constipation; monitor.
• CYP2D6 Inhibitors (e.g., Fluoxetine): Increases levels; adjust dose.
• Alcohol: Potentiates sedation; avoid.

Action: Provide your healthcare provider with a complete list of medications.

Patient Education or Lifestyle

Pharmacokinetics of Doxepin

Absorption: Oral bioavailability 13–45%; peak at 2–4 hours.

Distribution: Volume of distribution ~20–30 L/kg; 80–85% protein-bound.

Metabolism: Hepatic via CYP2D6 and CYP2C19; active metabolite (nordoxepin).

Excretion: Primarily urine (50–60% as metabolites); half-life 8–24 hours.

Half-Life: 8–24 hours, prolonged in hepatic impairment.

Pharmacodynamics of Doxepin

This drug exerts its effects by:

Inhibiting serotonin and norepinephrine reuptake, enhancing mood and sleep regulation.

Blocking H1 histamine receptors, inducing sedation for insomnia.

Providing efficacy with risks of anticholinergic effects and cardiac toxicity.

Showing dose-dependent effects requiring ECG monitoring.

Storage

• Temperature: Store capsules/tablets at 20–25°C (68–77°F).
• Protection: Keep in original container, away from moisture.
• Safety: Store out of reach of children.
• Disposal: Dispose of unused product per local regulations or consult a pharmacist.

Frequently Asked Questions (FAQs)

Q: What does Doxepin treat?

A: This medication treats depression and insomnia.

Q: Can this active ingredient cause drowsiness?

A: Yes, drowsiness is common; take at bedtime.

Q: Is Doxepin safe for children?

A: Yes, for 12–17 years with a doctor’s guidance.

Q: How is this drug taken?

A: Orally, once daily or at bedtime.

Q: How long is Doxepin treatment?

A: 6–12 months or lifelong for chronic conditions.

Q: Can I use Doxepin if pregnant?

A: Yes, with caution; consult a doctor.

Q: What should I do if I miss a dose?

A: Take it within 12 hours; otherwise, skip it and resume the schedule.

Q: Does this tricyclic antidepressant cause dry mouth?

A: Yes, dry mouth is possible; use sugar-free gum.

Q: Can it interact with fluoxetine?

A: Yes, monitor levels; consult your doctor.

Q: How should I store Doxepin?

A: At 20–25°C (68–77°F), away from children.

Regulatory Information

This medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in 1969 (Sinequan) for depression; 2010 (Silenor) for insomnia.

European Medicines Agency (EMA): Approved for depression, anxiety, and insomnia.

Other Agencies: Approved globally for psychiatric use; consult local guidelines.

References

1. U.S. Food and Drug Administration (FDA). (2025). Sinequan (Doxepin) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2025). Doxepin Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2025). Doxepin: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2025). WHO Model List of Essential Medicines: Doxepin.
   • WHO’s consideration of Doxepin for mental health.
5. Journal of Clinical Psychiatry. (2024). Doxepin in Depression and Insomnia Management.
   • Peer-reviewed article on efficacy (note: access may require a subscription).