Is doxepin (Sinequan) used for insomnia?

From the Guidelines

Yes, doxepin is used for sleep, specifically for treating insomnia characterized by difficulty with sleep maintenance. It is available as a low-dose formulation (Silenor) typically prescribed at 3-6 mg taken within 30 minutes of bedtime, as suggested by the American Academy of Sleep Medicine clinical practice guideline 1. The medication should be taken at least 3 hours after a meal for optimal absorption. Doxepin works by blocking histamine H1 receptors in the brain, which helps promote sleep. Unlike many other sleep medications, low-dose doxepin has minimal risk of dependence, tolerance, or withdrawal effects, as noted in a systematic review comparing its efficacy with placebo in persons diagnosed with insomnia disorder 1. It also doesn't typically cause morning grogginess when used at recommended doses. Side effects may include drowsiness, dry mouth, and dizziness. Patients should avoid alcohol while taking doxepin, as this combination can increase sedation. Those with narrow-angle glaucoma, severe urinary retention, or certain heart conditions should not use doxepin. While higher doses of doxepin are used as an antidepressant, the lower doses used for insomnia primarily target the sleep-promoting histamine system rather than affecting mood regulation. Key considerations for prescribing doxepin include its efficacy in improving sleep quality and duration, as well as its relatively favorable safety profile compared to other sleep medications, as discussed in the management of chronic insomnia disorder and obstructive sleep apnea guidelines 1. The use of doxepin for sleep maintenance insomnia is supported by clinical guidelines and evidence from systematic reviews, making it a viable treatment option for patients with this condition. Some important points to consider when prescribing doxepin for sleep include:

• Starting with a low dose (3 mg) and titrating as needed to minimize side effects
• Avoiding use in patients with certain medical conditions, such as narrow-angle glaucoma or severe urinary retention
• Counseling patients on the potential risks and benefits of doxepin, including its relatively low risk of dependence and withdrawal effects
• Monitoring patients for adverse events, such as drowsiness, dry mouth, and dizziness, and adjusting the dose or discontinuing treatment as needed.

From the FDA Drug Label

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 is used for sleep disturbances associated with psychoneurotic patients with depression and/or anxiety.

• Key points:
  • Doxepin is used to treat sleep disturbances.
  • It is recommended for the treatment of psychoneurotic patients with depression and/or anxiety.
  • The drug label does not provide information on the use of doxepin as a primary treatment for sleep disorders, but rather as a treatment for sleep disturbances associated with other conditions 2.

From the Research

Doxepin for Sleep

• Doxepin is used for the treatment of insomnia, as it binds with high specificity and affinity to the histamine H(1) receptor, promoting the initiation and maintenance of sleep 3.
• Low-dose doxepin (3 or 6 mg) has been shown to improve wake time after sleep onset, total sleep time, and sleep efficiency in adult or elderly patients with chronic primary insomnia 3.
• Studies have found that low-dose doxepin is effective in improving sleep maintenance and sleep duration, but not sleep initiation, with a small to medium effect size against placebo 4.
• Doxepin has been found to be safe and effective in improving sleep for 1-2 nights, with headache and somnolence being the most common side effects 4.

Efficacy and Safety

• Low-dose doxepin has been shown to provide sustained sleep improvement with a safety profile comparable to placebo in older adults 5.
• A systematic review and network meta-analysis found that low-dose doxepin was ranked as the optimal therapy for prolonging objective and subjective total sleep time in older adults 6.
• Doxepin has been found to be effective in increasing objective sleep efficiency, with a low risk of adverse events compared to other hypnotics 6.

Clinical Trials

• A placebo-controlled, double-blind, polysomnographic study found that doxepin significantly increased sleep efficiency after acute and subchronic intake in patients with primary insomnia 7.
• The study also found that doxepin caused significantly better global improvement at the first day of treatment, and patients rated sleep quality and working ability to be significantly improved by doxepin during the whole treatment period 7.