Can Doxylamine (DORAs) be used long-term for insomnia?

From the Guidelines

DORAs should not be used long-term for insomnia due to insufficient evidence on their safety and efficacy for extended periods. The FDA has approved pharmacologic therapy, including DORAs, for short-term use (4 to 5 weeks) and recommends that patients with insomnia that does not remit within 7 to 10 days of treatment should be further evaluated 1. Key points to consider when prescribing DORAs for insomnia include:

• The FDA suggests dosages lower than those used in many of the included studies, especially for older adults 1.
• Evidence is insufficient to evaluate the balance of the benefits and harms of long-term use of pharmacologic treatments in adults with chronic insomnia disorder 1.
• Patients should be monitored for side effects, including daytime impairment, “sleep driving,” behavioral abnormalities, and worsening depression 1.
• DORAs should be used as part of a comprehensive approach to insomnia that includes good sleep hygiene practices and addressing underlying causes of sleep disturbance.
• Discontinuation should be gradual rather than abrupt to minimize potential withdrawal effects. Some important considerations for the use of DORAs in clinical practice include:
• Typical dosing ranges for approved DORAs, such as suvorexant, lemborexant, and daridorexant, and their potential side effects.
• The importance of regular monitoring and follow-up to assess the effectiveness and safety of DORAs in individual patients.
• The need for further research to determine the long-term safety and efficacy of DORAs for insomnia treatment.

From the Research

Long-Term Use of DORAs for Insomnia

• The use of Dual Orexin Receptor Antagonists (DORAs) for insomnia has been studied in various research papers, with some indicating their potential for long-term use 2.
• According to a 2023 study, some classes of insomnia medications, such as non-benzodiazepines hypnotics, including DORAs, have been shown to be effective and safe for long-term use in the appropriate clinical setting 2.
• The FDA label for DORAs, such as eszopiclone, doxepin, ramelteon, does not specify that their use should be of a limited duration, suggesting their potential for long-term use 2.
• However, another study from 2009 notes that there is only very limited evidence that benzodiazepine receptor agonists, a class of medications that includes DORAs, retain their efficacy during long-term treatment 3.
• A 2021 review of pharmacological management of insomnia suggests that the decision to treat chronic insomnia disorder with long-term hypnotics, including DORAs, should be individualized and balance the potential risks of continuing medication use with the risks of untreated persistent insomnia and associated functional limitations 4.

Comparison with Other Treatments

• Cognitive Behavioral Therapy for Insomnia (CBT-I) is a non-pharmacological treatment that has been shown to be effective in treating insomnia, with a large evidence base and recent recommendation as the first line intervention for insomnia 5.
• A 2018 study comparing antidepressants for insomnia found that some antidepressants, such as trazodone and doxepin, may be effective in improving sleep quality, but the evidence is uncertain and limited by design limitations and short-term follow-up 6.
• The use of DORAs for insomnia should be considered in the context of other available treatments, including CBT-I and antidepressants, and individualized based on patient needs and preferences.