What is the drug class and use of Doxepin (tricyclic antidepressant)?

From the Guidelines

Doxepin is a tricyclic antidepressant (TCA) medication primarily used to treat depression, anxiety disorders, and certain sleep disorders, with a recommended dose of 3-6 mg for insomnia, marketed as Silenor, due to its strong antihistamine properties and sedative effects. The use of doxepin is guided by its pharmacological properties, including its ability to increase levels of norepinephrine and serotonin in the brain, which regulate mood, anxiety, and sleep 1.

Key Considerations for Doxepin Use

• For depression and anxiety, doxepin is typically prescribed at doses ranging from 25-300 mg daily, often starting at a lower dose and gradually increasing.
• Doxepin has strong antihistamine properties, which contribute to its sedative effects and usefulness for sleep disorders.
• Common side effects include drowsiness, dry mouth, constipation, blurred vision, and urinary retention due to its anticholinergic properties.
• Doxepin should be used cautiously in patients with heart conditions, glaucoma, urinary retention, or seizure disorders, as noted in guidelines for managing neuropathic pain and other conditions 1.
• It should not be combined with MAO inhibitors and requires careful tapering when discontinuing to avoid withdrawal symptoms.

Clinical Guidelines and Evidence

The clinical guideline for the evaluation and management of chronic insomnia in adults recommends considering sedating antidepressants, such as doxepin, especially when used in conjunction with treating comorbid depression/anxiety 1. However, the most recent and highest quality study regarding the specific use of doxepin in the context provided is not directly available in the given evidence, but based on the information about its pharmacological properties and clinical use, doxepin is particularly effective for insomnia treatment because it doesn't develop tolerance or dependence issues common with other sleep medications.

Important Safety Considerations

When prescribing doxepin, especially for patients with complex medical conditions or those taking other medications, it's crucial to consider potential interactions and side effects, as outlined in recommendations for the pharmacological management of neuropathic pain and other conditions 1. This includes careful consideration of cardiac toxicity, especially in patients with ischemic cardiac disease or ventricular conduction abnormalities, and the need for screening electrocardiograms in patients over 40 years old.

From the FDA Drug Label

Doxepin hydrochloride, USP is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic compounds. The mechanism of action of Doxepin HCl is not definitely known. It is not a central nervous system stimulant nor a monoamine oxidase inhibitor 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 drug class of Doxepin is a tricyclic antidepressant. The use of Doxepin includes:

• Treatment of psychoneurotic patients with depression and/or anxiety
• Treatment of depression and/or anxiety associated with alcoholism, organic disease, or psychotic depressive disorders 2 2

From the Research

Drug Class and Use of Doxepin

• Doxepin is a tricyclic antidepressant that combines antidepressant activity with a sedative effect, similar to amitriptyline 3.
• It is used to treat depression, anxiety, and insomnia, with its sedative properties making it more useful in depressed patients with sleep disturbances 3, 4, 5, 6.
• Doxepin has been shown to be effective in treating primary insomnia, with low-dose doxepin (1,3, and 6 mg) being used as a preferential H1 antagonist for this purpose 4, 5, 6.
• The drug has a unique potency and selectivity for antagonizing the H1 (histamine) receptor at low doses, which may prove advantageous compared to other medications for insomnia 6.
• Doxepin is usually well-tolerated, with side effects similar to those of other tricyclic antidepressants, including dry mouth, drowsiness, and constipation 3.
• The therapeutic range of doxepin plasma concentrations is not well-established, with some studies suggesting a range of 50 to 250 ng/mL 7.

Mechanism of Action and Pharmacological Properties

• Doxepin has a subnanomolar affinity for the histamine H(1) (H(1)) receptor, which contributes to its sedative effects 5.
• The drug also has anticholinergic and antinoradrenergic properties, which can lead to dose-limiting side effects at higher doses 4.
• Doxepin's mechanism of action as a tricyclic antidepressant involves the inhibition of serotonin and norepinephrine reuptake, which contributes to its antidepressant effects 3.

Clinical Use and Efficacy

• Doxepin has been shown to be effective in treating depression, anxiety, and insomnia in various clinical studies 3, 4, 5, 6.
• The drug is often used in patients with sleep disturbances, as its sedative properties can help improve sleep quality 3, 4, 5, 6.
• Doxepin has been compared to other medications, such as benzodiazepines, and has been found to be more effective in treating anxiety accompanied by significant depression 3.