What medication is more effective for maintaining sleep (staying asleep) rather than initiating sleep (falling asleep)?

From the Guidelines

For staying asleep rather than falling asleep, doxepin is the most suitable medication option, as it is specifically approved for sleep maintenance and works by blocking histamine receptors that promote wakefulness, as suggested by the American Academy of Sleep Medicine clinical practice guideline 1. When considering medications for sleep maintenance, it's essential to distinguish between sleep onset and sleep maintenance insomnia.

• Sleep onset insomnia refers to difficulty falling asleep, while sleep maintenance insomnia refers to difficulty staying asleep throughout the night.
• Medications like zolpidem (Ambien) and zaleplon (Sonata) are designed to help with sleep onset, with shorter half-lives that allow for quicker wake-up times.
• In contrast, medications like doxepin (Silenor) and suvorexant are better suited for sleep maintenance, as they remain active in the system longer and address the brain mechanisms responsible for nighttime awakenings. The American Academy of Sleep Medicine clinical practice guideline suggests that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults, based on trials of 3 mg and 6 mg doses of doxepin 1.
• Doxepin at low doses (3-6mg) is specifically approved for sleep maintenance and works by blocking histamine receptors that promote wakefulness.
• Suvorexant, an orexin receptor agonist, is also suggested as a treatment for sleep maintenance insomnia, based on trials of 10,15/20, and 20 mg doses 1. For optimal results, it's recommended to take these sleep maintenance medications 30-60 minutes before bedtime and maintain good sleep hygiene practices, such as keeping a consistent sleep schedule and avoiding screens before bed.

From the FDA Drug Label

The effect of eszopiclone on reducing sleep latency and improving sleep maintenance was established in studies with 2100 subjects (ages 18 to 86) with chronic and transient insomnia in six placebo-controlled trials of up to 6 months’ duration. Eszopiclone significantly decreased sleep latency and improved measures of sleep maintenance (objectively measured as wake time after sleep onset [WASO] and subjectively measured as total sleep time). The 3 mg dose was superior to placebo on WASO In the second study, adults with chronic insomnia (n=788) were evaluated using subjective measures in a double-blind, parallel-group trial comparing the safety and efficacy of eszopiclone 3 mg with placebo administered nightly for 6 months. Eszopiclone was superior to placebo on subjective measures of sleep latency, total sleep time, and WASO

Eszopiclone is better for staying asleep rather than falling asleep, as it improves sleep maintenance by decreasing wake time after sleep onset (WASO) and increasing total sleep time 2.

• Key benefits of eszopiclone include:
  • Improved sleep maintenance
  • Decreased wake time after sleep onset (WASO)
  • Increased total sleep time However, it is essential to consider the potential next-day residual effects, such as psychomotor and memory impairment, when using eszopiclone 2.

From the Research

Medication Options for Staying Asleep

• Eszopiclone is a non-benzodiazepine hypnotic agent that has been shown to be effective in improving sleep maintenance, in addition to sleep onset, in adults and elderly patients with primary insomnia 3, 4, 5, 6.
• Studies have demonstrated that eszopiclone 2 mg and 3 mg doses can significantly reduce the number of awakenings and wake time after sleep onset, while increasing total sleep time and quality of sleep 3, 4, 5.
• Eszopiclone has been found to be well-tolerated, with no evidence of tolerance or rebound insomnia during long-term treatment, making it a useful therapeutic option for patients requiring prolonged treatment 3, 4, 6.
• Ramelteon, a selective MT1 and MT2 receptor agonist, has also been shown to be effective in improving sleep quality and reducing sleep onset time, but its efficacy in staying asleep has not been directly compared to eszopiclone 7.

Comparison of Medications

• Eszopiclone has been compared to other non-benzodiazepine hypnotics, such as zolpidem and zaleplon, but direct comparisons of their efficacy in staying asleep are limited 4, 6.
• Melatonin and melatonergic drugs, such as ramelteon and agomelatine, have been found to be effective in improving sleep quality, but their efficacy in staying asleep has not been directly compared to eszopiclone 7.

Dosage and Administration

• The recommended starting dose of eszopiclone for difficulty falling asleep is 1 mg at bedtime, while a dose of 2 mg is recommended for patients who have difficulty maintaining sleep 5.
• Eszopiclone should be taken orally, once nightly, and its dosage may need to be adjusted in patients with renal or hepatic impairment, or in those taking concurrent medications that interact with eszopiclone 3, 5.