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
Seek immediate medical attention for:
- Cardiac: QT prolongation or arrhythmias.
- Neurologic: Seizures or serotonin syndrome.
- Psychiatric: Suicidal ideation or mania.
- Allergic: Anaphylaxis or severe rash.
- Gastrointestinal: Paralytic ileus.
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
Medication Adherence: Take this tricyclic antidepressant as prescribed to manage depression or insomnia, following the exact schedule.
Monitoring: Report drowsiness, mood changes, or suicidal thoughts immediately.
Lifestyle: Avoid alcohol and high-risk activities; maintain hydration.
Diet: Take with or without food; avoid heavy meals.
Emergency Awareness: Know signs of overdose or cardiac issues; seek care if present.
Follow-Up: Schedule regular check-ups every 1–2 weeks to monitor ECG, liver function, and mood.
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
- U.S. Food and Drug Administration (FDA). (2025). Sinequan (Doxepin) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2025). Doxepin Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2025). Doxepin: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2025). WHO Model List of Essential Medicines: Doxepin.
- WHO’s consideration of Doxepin for mental health.
- Journal of Clinical Psychiatry. (2024). Doxepin in Depression and Insomnia Management.
- Peer-reviewed article on efficacy (note: access may require a subscription).
