What are the uses and dosing recommendations for Doxepin (tricyclic antidepressant) in treating depression, anxiety disorders, and sleep disorders?

From the Guidelines

Doxepin is recommended for the treatment of insomnia at a low dose of 3-6 mg, taken 30 minutes before bedtime, due to its efficacy in improving sleep maintenance with minimal side effects, as supported by the American Academy of Sleep Medicine clinical practice guideline 1. The typical starting dose for depression and anxiety is 25-50 mg daily, taken at bedtime, gradually increasing to 75-150 mg daily if needed, with a maximum dose of 300 mg daily for severe depression. For insomnia, low-dose doxepin (3-6 mg) is recommended, as these lower doses target histamine receptors to promote sleep without significant anticholinergic side effects. Treatment duration for depression typically continues for at least 6-12 months after symptom resolution, while anxiety treatment may last 6 months or longer depending on response. For insomnia, short-term use of 7-10 days is initially recommended, with reassessment for longer use. Doxepin works by inhibiting the reuptake of serotonin and norepinephrine, increasing their availability in the brain, while its sedating properties stem from antagonism of histamine H1 receptors. Common side effects include drowsiness, dry mouth, constipation, blurred vision, and orthostatic hypotension. Caution is advised in patients with cardiovascular disease, glaucoma, urinary retention, or those taking other medications that affect serotonin levels, as noted in the clinical guideline for the evaluation and management of chronic insomnia in adults 1. Additionally, the choice of a specific medication may depend on the patient's response to the first treatment, with considerations for longer-acting hypnotics or shorter-acting drugs, as discussed in the pharmaceutical therapy options for insomnia 1. The American Academy of Sleep Medicine clinical practice guideline also recommends considering the benefits and harms of doxepin, with the task force judging that the benefits outweigh the harms for the treatment of insomnia 1.

From the FDA Drug Label

Doxepin Hydrochloride Capsules, USP are recommended for the treatment of:

1. Psychoneurotic patients with depression and/or anxiety.
2. Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol).
3. Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly).
4. Psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders For most patients with illness of mild to moderate severity, a starting daily dose of 75 mg is recommended Dosage may subsequently be increased or decreased at appropriate intervals and according to individual response. The usual optimum dose range is 75 mg/day to 150 mg/day. In more severely ill patients higher doses may be required with subsequent gradual increase to 300 mg/day if necessary.

Uses of Doxepin:

• Treatment of psychoneurotic patients with depression and/or anxiety
• Treatment of depression and/or anxiety associated with alcoholism, organic disease, or psychotic depressive disorders Dosing Recommendations:
• Starting daily dose: 75 mg for patients with mild to moderate severity
• Optimum dose range: 75 mg/day to 150 mg/day
• Maximum dose: 300 mg/day for severely ill patients Key Considerations:
• Dosage may be increased or decreased according to individual response
• Higher doses may be required for more severely ill patients
• Doxepin is not approved for use in pediatric patients 2 2

From the Research

Uses of Doxepin

• Doxepin is a tricyclic antidepressant used to treat depression, anxiety disorders, and sleep disorders 3.
• It combines antidepressant activity with a sedative effect, making it useful in depressed patients with sleep disturbances and in depression associated with anxiety 3.
• Doxepin is more effective than chlordiazepoxide or diazepam when anxiety is accompanied by significant depression 3.

Dosing Recommendations

• The usual dosage of doxepin for treating depression and anxiety disorders is not specified in the provided studies, but low-dose doxepin (12.5 mg/day) has been shown to be effective in improving sleep quality and anxiety in patients with comorbid insomnia and anxiety disorders 4.
• Doxepin tends to cause fewer or less troublesome side-effects than other tricyclic antidepressants, such as imipramine and amitriptyline, at dosages that achieve a similar overall response rate 3.

Side Effects and Safety

• Common side effects of doxepin include dry mouth, drowsiness, and constipation 3.
• Postural hypotension is uncommon, but doxepin can cause cardiovascular side-effects in overdosage, similar to other tricyclic antidepressants 3.
• Doxepin is usually well tolerated, particularly by the elderly and those with cardiovascular disease 3.

Comparison with Other Treatments

• Doxepin has been compared to other antidepressants, such as citalopram, in terms of its efficacy and safety in treating comorbid insomnia and anxiety disorders 4.
• Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are also used to treat mood and anxiety disorders, but their mechanisms of action and side effect profiles differ from those of doxepin 5, 6, 7.