What is the use of Doxepin (tricyclic antidepressant)?

From the Guidelines

Doxepin is primarily used to treat depression, anxiety disorders, and insomnia, with a low dose of 3-6 mg being effective for insomnia, as evidenced by a clinical practice guideline from the American Academy of Sleep Medicine 1. The medication works by increasing levels of norepinephrine and serotonin in the brain, which helps regulate mood and sleep patterns. For depression and anxiety, typical dosing ranges from 75-150 mg daily, often starting at a lower dose of 25-50 mg and gradually increasing. However, for insomnia, the much lower dose of 3-6 mg is used, taken 30 minutes before bedtime, with meta-analysis showing moderate improvement in sleep quality at 3 mg and mild improvement at 6 mg 1. Side effects commonly include drowsiness, dry mouth, blurred vision, constipation, urinary retention, and potential cardiac effects like tachycardia. Patients should be aware that doxepin has significant anticholinergic properties and should be used cautiously in elderly patients or those with certain medical conditions like glaucoma, prostatic hypertrophy, or cardiac issues. When discontinuing doxepin, it should be tapered gradually rather than stopped abruptly to avoid withdrawal symptoms. Patients should avoid alcohol while taking this medication and inform their healthcare provider of all other medications they're taking to prevent potential drug interactions, particularly with MAO inhibitors. Additionally, doxepin may also be used to treat mast cell activation syndrome (MCAS), with its potent H1 & H2 antihistamine activity, although it may cause drowsiness and cognitive decline, particularly in the elderly 1. Some key points to consider when prescribing doxepin include:

• Starting with a low dose and gradually increasing as needed
• Monitoring for side effects, particularly anticholinergic effects
• Avoiding use in patients with certain medical conditions, such as glaucoma or cardiac issues
• Tapering the medication gradually when discontinuing to avoid withdrawal symptoms
• Informing patients of potential drug interactions, particularly with MAO inhibitors.

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

The use of Doxepin, a tricyclic antidepressant, is for the treatment of:

• Psychoneurotic patients with depression and/or anxiety
• Depression and/or anxiety associated with alcoholism, organic disease, or psychotic depressive disorders
• Anxiety and depression in various clinical settings, as specified in the label 2

From the Research

Uses of Doxepin

• Doxepin is a tricyclic antidepressant that combines antidepressant activity with a sedative effect, making it useful for treating depression, especially in patients with sleep disturbances and anxiety 3.
• It is effective in improving sleep quality in patients with comorbid insomnia and anxiety disorders, with low-dose doxepin (12.5 mg/day) significantly improving sleep latency, duration, and disturbances 4.
• Doxepin has been used to treat insomnia, with low-dose doxepin (less than 25 mg/day) showing promise as a preferential H1 antagonist for the treatment of primary insomnia, particularly for sleep maintenance insomnia 5.
• In depressed patients suffering from insomnia, low-dose doxepin has shown mixed results, with some studies indicating no significant improvement in sleep onset or maintenance 6, while others have found significant improvements in sleep efficiency and depression 7.

Therapeutic Efficacy

• Doxepin has been found to be effective in treating depression, with a mood-elevating effect similar to that of other tricyclic antidepressants, although it may be slower to take effect than some other medications 3.
• The sedative properties of doxepin make it more useful than some other antidepressants in patients with anxiety and sleep disturbances 3.
• Doxepin has been shown to be well-tolerated, with fewer side effects than some other tricyclic antidepressants, although it can cause dry mouth, drowsiness, and constipation 3.

Clinical Applications

• Doxepin may be used to treat patients with comorbid insomnia and anxiety disorders, particularly those who have not responded to other treatments 4.
• Low-dose doxepin may be used to treat primary insomnia, particularly in patients who have difficulty maintaining sleep 5.
• Doxepin may be used to treat depression in patients with sleep disturbances, although its efficacy in this population may vary 6, 7.