Can doxepin (a tricyclic antidepressant) be taken as needed (prn) for insomnia and anxiety?

From the Guidelines

Doxepin can be taken as needed (PRN) for insomnia, but its use for anxiety is generally not recommended on an as-needed basis. For insomnia, low-dose doxepin (3-6 mg) taken 30 minutes before bedtime can be effective for occasional use, as it works by blocking histamine H1 receptors, which helps induce sleep without causing significant next-day drowsiness at these low doses 1. However, for anxiety, doxepin is typically prescribed as a regular daily medication (starting at 25-50 mg and potentially increasing to 75-150 mg) rather than on an as-needed basis because it requires consistent blood levels to effectively manage anxiety symptoms. This is due to its mechanism as a tricyclic antidepressant that affects serotonin and norepinephrine levels in the brain, which takes time to achieve therapeutic effect. Some key points to consider when prescribing doxepin for insomnia include:

• The medication should be taken at a low dose (3-6 mg) to minimize side effects
• It should be taken 30 minutes before bedtime to help induce sleep
• Patients with glaucoma, urinary retention issues, or certain heart conditions should use doxepin with caution
• Doxepin should not be combined with MAO inhibitors It's also important to note that cognitive behavioral therapy for insomnia (CBT-I) is a recommended treatment for chronic insomnia disorder, and can be used in conjunction with pharmacologic therapy or as a standalone treatment 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).
2. Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly).
3. Psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders The target symptoms of psychoneurosis that respond particularly well to Doxepin Hydrochloride Capsules, USP include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry.

Doxepin can be used for the treatment of anxiety and insomnia associated with psychoneurotic disorders or depression. However, the label does not explicitly state that it can be taken prn (as needed) for these conditions.

• The recommended use is for the treatment of specific conditions, including psychoneurotic patients with depression and/or anxiety.
• There is no explicit mention of prn dosing for insomnia and anxiety in the provided drug labels 2 2.

From the Research

Dosage and Administration

• Doxepin can be taken at a low dose (3-6 mg) for the treatment of insomnia, as approved by the U.S. Food and Drug Administration (FDA) 3.
• Low-dose doxepin (12.5 mg/day) has been shown to significantly improve sleep latency, duration, and disturbances, as well as daytime dysfunction and the global Pittsburgh Sleep Quality Index in patients with comorbid insomnia and anxiety disorders 4.
• Doxepin can be considered as a first-line agent for older adults with insomnia, and for those who have difficulty staying asleep, low-dose doxepin should be considered 5.

Efficacy and Safety

• Low-dose doxepin has been found to have a small to medium effect size against placebo for sleep maintenance and sleep duration, but not for sleep initiation 3.
• Doxepin has been shown to improve anxiety in patients with comorbid insomnia and anxiety disorders, with a significant and positive correlation between the improvement in sleep quality and anxiety 4.
• Low-dose doxepin has been found to be safe and effective in improving sleep, with no significant next-day residual effect and common side effects including headache and somnolence 3.

Comparison with Other Treatments

• Cognitive Behavioral Therapy for Insomnia (CBT-i) is now commonly recommended as first-line treatment for chronic insomnia, with studies showing its efficacy in improving sleep onset latency, wake after sleep onset, total sleep time, and sleep efficiency 6.
• CBT-i has been found to be an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes and no adverse outcomes reported 6.
• Acceptance and Commitment Therapy has been proposed as a novel approach to address both the underlying condition (insomnia/anxiety) and the substance-related disorder, with potential benefits for discontinuing long-term benzodiazepine use 7.