What is the best treatment for Non-24-Hour Sleep-Wake Disorder (Non-24), a circadian rhythm disorder?

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Last updated: April 27, 2025 • View editorial policy

From the Guidelines

The most effective treatment for Non-24-Hour Sleep-Wake Rhythm Disorder (Non-24) is the use of tasimelteon (Hetlioz), a melatonin agonist, which has been FDA-approved for the treatment of Non-24 in blind individuals, as it has been shown to safely and effectively entrain the circadian rhythm in 20% of patients compared to 3% with placebo 1.

Treatment Approach

For sighted individuals, a combination of timed light therapy and melatonin supplementation can be used.

  • Light therapy involves using a bright light box (10,000 lux) for 30-60 minutes each morning at a consistent time to help reset the circadian rhythm.
  • Melatonin supplementation of 0.5-5mg should be taken 1-2 hours before the desired bedtime.

Additional Recommendations

Maintaining strict sleep hygiene is essential, including:

  • Consistent sleep-wake times
  • Avoiding caffeine and alcohol before bed
  • Creating a dark, quiet sleeping environment Regular daily routines for meals and exercise also help reinforce circadian cues.

Rationale

These treatments work by strengthening circadian signals to the brain's suprachiasmatic nucleus, which controls the body's internal clock. Without treatment, the sleep-wake cycle will continue to drift, causing periods of insomnia alternating with excessive daytime sleepiness that can significantly impact quality of life. It is crucial to note that the optimal dosing of melatonin may vary between individuals, and future studies should aim to identify the lowest effective melatonin dosage and duration of treatment 1. Additionally, the use of melatonin agonists like tasimelteon may offer a promising treatment option, and further research is needed to determine their efficacy and safety in different populations 1.

From the FDA Drug Label

The effectiveness of tasimelteon in the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24) was established in two randomized double-masked, placebo-controlled, multicenter, parallel-group studies (Studies 1 and 2) in totally blind patients with Non-24 In study 1, 84 patients with Non-24 (median age 54 years) were randomized to receive tasimelteon 20 mg or placebo, one hour prior to bedtime, at the same time every night for up to 6 months. Treatment with tasimelteon resulted in a significant improvement, compared with placebo, for both nighttime total sleep time and daytime nap duration in Study 1 and Study 2

The best way to treat non-24-hour circadian rhythm disorder is with tasimelteon 20 mg taken one hour prior to bedtime, at the same time every night 2. Key benefits of this treatment include:

  • Significant improvement in nighttime total sleep time
  • Significant improvement in daytime nap duration
  • Established efficacy in two randomized double-masked, placebo-controlled studies 2

From the Research

Treatment Options for Non-24 Hour Circadian Rhythm Disorder

  • Orally administered melatonin and the melatonin agonist tasimelteon have been shown to entrain the circadian clock, resulting in improvements in night-time sleep and daytime alertness 3, 4, 5
  • The time of melatonin or tasimelteon administration must be considered carefully, with low-dose melatonin administered about 6 hours before the desired bedtime for most individuals, and at the desired wake time for those with circadian periods shorter than 24 hours 3
  • Tasimelteon has been administered 1 hour before the target bedtime in patients with non-24 hour circadian rhythm disorder, with comparable rates of treatment success to melatonin 3, 4
  • Bright light therapy may also be used in combination with timed melatonin to aid in entrainment, particularly in sighted individuals with non-24 hour circadian rhythm disorder 6

Considerations for Treatment

  • Issues of cost, dose accuracy, and purity may influence the decision to use tasimelteon or melatonin to treat non-24 hour circadian rhythm disorder 3
  • The diagnosis of non-24 hour circadian rhythm disorder can be challenging due to cyclical symptoms, and should be confirmed by measurements of circadian biomarkers such as urinary melatonin 5
  • Long-term effectiveness of treatment may be limited due to the need for ongoing behavioral and environmental structure to maintain stable entrainment 6

Available Treatments

  • Tasimelteon is available as a capsule in a single 20-mg dose, and must be obtained through a specialty pharmacy program 4
  • Melatonin is available in various doses and formulations, and may be preferred due to cost and availability considerations 3, 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.