Usage
Doxepin is prescribed for the treatment of:
- Major depressive disorder
- Anxiety disorders
- Insomnia (specifically for sleep maintenance)
- Itching associated with atopic dermatitis or lichen simplex chronicus (topical formulation)
Pharmacological classification: Tricyclic antidepressant (TCA)
Mechanism of action (brief): Doxepin primarily acts by antagonizing histamine H1 receptors in the brain, promoting sleep. It also inhibits the reuptake of serotonin and norepinephrine, contributing to its antidepressant and anxiolytic effects. For topical use, doxepin acts as a potent antihistamine, relieving itching.
Alternate Names
While “doxepin” is the generic name, Silenor is a brand name specifically for the low-dose formulation used to treat insomnia. Other brand names exist internationally.
How It Works
Pharmacodynamics: Doxepin blocks histamine H1 receptors, serotonin transporters (SERT), and norepinephrine transporters (NET). The H1 antagonism is responsible for its sedative effects at low doses. Higher doses, by affecting SERT and NET, yield antidepressant and anxiolytic action. Topical doxepin exerts its antipruritic effect through peripheral H1 receptor blockade.
Pharmacokinetics:
- Absorption: Doxepin is well-absorbed orally. Food can delay absorption but does not significantly affect bioavailability. Topical doxepin has minimal systemic absorption.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6 and CYP2C19.
- Elimination: Excreted mainly in urine, some in feces.
Mode of action: Binds to and blocks H1 receptors, SERT, and NET, preventing the binding of respective neurotransmitters/ligands.
Elimination pathways: Hepatic metabolism (CYP2D6, CYP2C19, CYP3A4, CYP1A2), followed by renal excretion.
Dosage
Standard Dosage
Adults:
- Depression/Anxiety: Initial dose 25 mg/day, gradually titrated up every 5-7 days as needed. Usual range: 75-150 mg/day (up to 300 mg/day in divided doses for severe cases). Single bedtime dose up to 150 mg.
- Insomnia (Silenor): 3-6 mg once daily, 30 minutes before bedtime.
Children:
Not generally recommended for children under 12 years of age for depression or anxiety. For atopic dermatitis (topical), children over 12 can use the adult dose.
Special Cases:
- Elderly Patients: Start with lower doses (e.g., 3 mg for insomnia, 10-25 mg for depression/anxiety at bedtime) and titrate cautiously.
- Patients with Renal Impairment: Dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Start with lower doses and monitor closely.
- Patients with Comorbid Conditions: Exercise caution, especially with cardiovascular disease, as doxepin can cause orthostatic hypotension and other cardiac effects.
Clinical Use Cases
Doxepin does not have a direct indication for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Adjustments based on individual patient response, age, renal/hepatic function, and concomitant medications. Therapeutic drug monitoring can be helpful, particularly for patients with CYP2D6 or CYP2C19 polymorphisms.
Side Effects
Common Side Effects:
Drowsiness, dry mouth, dizziness, constipation, blurred vision, weight gain, urinary retention.
Rare but Serious Side Effects:
Cardiac arrhythmias, seizures, severe hypotension, serotonin syndrome (with interacting drugs), angle-closure glaucoma, neuroleptic malignant syndrome.
Long-Term Effects:
Tardive dyskinesia (rare), sexual dysfunction.
Adverse Drug Reactions (ADR):
Allergic reactions, agranulocytosis, cholestatic jaundice.
Contraindications
- Hypersensitivity to doxepin
- Recent myocardial infarction
- Angle-closure glaucoma
- Urinary retention
- Concomitant use of MAOIs
Drug Interactions
- MAOIs (contraindicated)
- CNS depressants (additive effects)
- Anticholinergic drugs (additive effects)
- CYP2D6 and CYP2C19 inhibitors/inducers (alter doxepin levels)
- Cimetidine (requires dose reduction of doxepin)
- Alcohol (additive CNS depression)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (consider risks and benefits).
- Breastfeeding: Doxepin is excreted in breast milk; potential for adverse effects in infants. Consider the risks and benefits or alternative safer options.
Drug Profile Summary
- Mechanism of Action: H1 receptor antagonist (at low doses for insomnia), SERT and NET inhibitor (at higher doses for depression/anxiety).
- Side Effects: Drowsiness, dry mouth, dizziness, constipation, blurred vision, orthostatic hypotension.
- Contraindications: Hypersensitivity, recent MI, angle-closure glaucoma, urinary retention, MAOI use.
- Drug Interactions: MAOIs, CNS depressants, anticholinergics, CYP2D6/CYP2C19 inhibitors/inducers, cimetidine, alcohol.
- Pregnancy & Breastfeeding: Category C; excreted in breast milk, exercise caution.
- Dosage: Varies depending on indication and patient. See Dosage section above.
- Monitoring Parameters: Cardiac function (ECG if needed), mental status, adverse effects.
Popular Combinations
Generally, doxepin is not combined with other antidepressants. However, it may be used in conjunction with other psychotropic medications like mood stabilizers or antipsychotics as part of a comprehensive treatment plan. For topical use, it is sometimes combined with corticosteroids.
Precautions
- Monitor for suicidal ideation, especially early in treatment.
- Pre-screening for cardiac, hepatic, and renal dysfunction is advisable.
- Caution in elderly patients and those with comorbid conditions.
- Avoid alcohol.
- May impair driving ability.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxepin?
A: The dosage varies depending on the indication. See Dosage section above for details.
Q2: What are the common side effects of Doxepin?
A: Common side effects include drowsiness, dry mouth, dizziness, constipation, blurred vision, and weight gain.
Q3: Can Doxepin be used during pregnancy?
A: Doxepin is Pregnancy Category C. Weigh the potential benefits against the risks. Consult with a specialist.
Q4: Does Doxepin interact with other medications?
A: Yes, see the Drug Interactions section for a detailed list. MAOIs are contraindicated.
Q5: How long does it take for Doxepin to work for depression?
A: The antidepressant effects of doxepin may take 2-3 weeks to become fully evident.
Q6: Can Doxepin be used for anxiety?
A: Yes, doxepin can be used to treat various anxiety disorders.
Q7: Is Doxepin addictive?
A: Doxepin does not typically cause physical dependence or addiction, but withdrawal symptoms can occur if it is stopped abruptly. It’s essential to taper the dose under medical supervision.
Q8: What should I do if I miss a dose of Doxepin?
A: Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not take two doses at the same time.
Q9: Can Doxepin be used to treat itching?
A: Yes, a topical cream formulation of doxepin is available to relieve itching associated with skin conditions like atopic dermatitis.
