What is the efficacy of Doxepin (tricyclic antidepressant) for treating insomnia?

From the Guidelines

Doxepin is an effective medication for treating insomnia, particularly for people who have difficulty staying asleep, with a recommended dose of 3-6 mg taken 30 minutes before bedtime, as supported by a low-quality systematic review that included 6 industry-sponsored RCTs 1. The efficacy of doxepin for insomnia is well-documented, with studies showing improved sleep outcomes, such as sleep efficiency, sleep onset latency, and total sleep time, compared to placebo 1. Some key points to consider when prescribing doxepin for insomnia include:

• Starting with a low dose of 3-6 mg and adjusting as needed, with a maximum dose not exceeding 6 mg daily
• Individualizing treatment duration, but generally limiting it to 7-10 days initially, with reassessment for continued use
• Avoiding alcohol while taking doxepin, as it can increase sedation
• Contraindicating doxepin in patients with narrow-angle glaucoma, severe urinary retention, or those taking MAO inhibitors
• Starting elderly patients at the lowest dose (3 mg) due to increased sensitivity
• Monitoring for common side effects, such as drowsiness, dry mouth, and dizziness It's also important to note that doxepin has minimal risk of dependence or tolerance, making it suitable for longer-term use when necessary, as opposed to other sleep medications 1. Overall, doxepin is a viable treatment option for insomnia, particularly for those who have difficulty staying asleep, and its efficacy and safety profile make it a suitable choice for patients who require ongoing treatment.

From the Research

Efficacy of Doxepin for Insomnia

• Doxepin, a sedating tricyclic drug, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of insomnia at doses of 3 mg and 6 mg 2.
• Studies have shown that low-dose doxepin has a small to medium effect size against placebo for sleep maintenance and sleep duration, but not for sleep initiation 2, 3.
• Doxepin 3 mg and 6 mg have been found to significantly reduce waking after sleep onset and increase total sleep time, with no significant difference between the two doses 3.
• The most common side effects of doxepin are somnolence and headache, with no significant next-day residual effects 2, 3.

Comparison with Other Treatments

• Doxepin has been compared to zolpidem in a study, which found that doxepin was more effective in improving executive function in patients with insomnia disorder 4.
• Doxepin has also been found to improve sleep quality and reduce wake after sleep onset, with a significant improvement in sleep efficiency compared to zolpidem 4.

Mechanism of Action

• Doxepin's efficacy in treating insomnia is thought to be due to its role as an H1 specific antagonist, which helps to regulate the sleep-wake cycle 5.
• The use of low-dose doxepin has been found to have preferential effects on sleep maintenance insomnia compared to sleep initiation 5.

Safety and Tolerability

• Doxepin has been found to be generally well-tolerated, with a low incidence of adverse events 2, 3.
• However, some studies have reported a higher incidence of adverse events with doxepin compared to other treatments, such as zolpidem 4.
• Rebound insomnia has been reported in some patients taking doxepin, particularly at higher doses 6.