Hetlioz vs. Melatonin for the Treatment of Non-24 in Blind People

How the Two Treatment Options Compare

Melatonin supplements are well-known for their ability to help you sleep. They remain the standard treatment for non-24-hour sleep-wake disorder (non-24). Non-24 is a disorder in which the body's own biological clock, or circadian rhythm, fails to align with the 24-hour day. The condition is most commonly seen in people who are visually impaired but sometimes in other groups too.

Hetlioz (tasimelteon) is a drug approved by the Food and Drug Administration (FDA) for the treatment of non-24 in adults, and also for the genetic Smith-Magenis Syndrome (SMS). It acts on brain receptors for the hormone melatonin and was more effective for treating non-24 than placebo pills ("sham" treatments) in studies for both conditions.

But the drug has not yet been directly compared to over-the-counter melatonin. This article looks at qualities and concerns about both products to help you better understand the choices.

Man sitting on edge of bed in middle of the night

PhotoAlto/Frederic Cirou / Getty Images

Non-24 Treatment Options

In its guideline update from 2015, published just after Hetlioz became available, the American Academy of Sleep Medicine (AASM) continued its recommendation to use melatonin for treating non-24. The supplement can work quite well to stabilize circadian rhythms that, because of sleep disruption, lead to cycles of insomnia and excessive sleepiness.

This stabilization is called entrainment. The rhythms of sleep and wakefulness in blind people can be aligned, or entrained, to the natural day-night patterns. This can be done with very low doses of over-the-counter melatonin, which generally costs far less than prescription Hetlioz does.

Because melatonin is sold as a supplement that's not regulated by the FDA, it is important to be sure of the quality and precise contents of the product. Many supplements have 10 times the melatonin needed to treat non-24, or even more. This may flood the body's system, limiting benefits and leading to side effects.

Some of these potential melatonin side effects include:

  • Changes in blood sugar levels
  • Changes in blood pressure
  • Stomach problems
  • Risk of bleeding, if taking certain drugs

Headaches and drowsiness may be seen when using either melatonin or Hetlioz. The other side effects of Hetlioz may include:

  • Increased liver enzymes
  • Nightmares or unusual dreams
  • Respiratory infections
  • Urinary tract infections  

The timing of the doses is key as well. It may be hard to "reset" the circadian rhythm using melatonin or Hetlioz, and problems may come back if a dose is skipped. A sleep specialist may help you decide between using melatonin or Hetlioz and help you know if the doses and timing are right.

Other Options

For people with non-24 who still have some vision, the AASM suggests timed light therapy may also help, whether it's natural or artificial light. The use of light may vary depending on the exact circadian disorder, so it's best to see a sleep specialist for advice.

Researchers are always looking at new ways to treat non-24. Among them is the use of Rozerem (ramalteon), a drug usually used to help people with insomnia fall asleep more easily. It's been tried in a case of non-24 when there is no visual impairment.

Assessing Treatment Effects

How do you know if the treatment is working? Most people with non-24 have cycles of insomnia and daytime sleepiness. This makes it hard to function on a typical schedule. The symptoms may shift in timing and intensity over weeks to months.

With both melatonin and Hetlioz, the hope is that baseline symptoms, such as problems paying attention or general irritability, should get better. Sleep logs and laboratory data, like tests for keeping track of the melatonin level in saliva, may prove helpful.


Non-24 is a condition most commonly seen in visually impaired people, in which the circadian rhythm "clock" is out of sync with the normal 24-hour-day schedule. Though the prescription drug Hetlioz has been approved to treat non-24, melatonin supplements are still the typical first-choice treatment.

However, melatonin supplements can vary in quality and can cause side effects, particularly if used in excess. It's important to work with a healthcare provider to find the best choice for treating non-24.

A Word From Verywell

Hopefully, further research will test Hetlioz and melatonin head-to-head. This research would give us an idea of what works best and why. It may also be possible to learn who will benefit more from using one or the other, giving you and your healthcare provider more information to make the best possible choices.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Organization for Rare Disorders. Non-24-hour sleep-wake disorder.

  2. U.S. Food and Drug Administration. Highlights of prescribing information.

  3. Auger R, Burgess H, Emens J, Deriy LV, Thomas SM, Sharkey KM. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders. J Clin Sleep Med. 2015;11(10):1199-1236. doi:10.5664/jcsm.5100

  4. Garaulet M, Qian J, Florez JC, Arendt J, Saxena R, Scheer FA. Melatonin effects on glucose metabolism: time to unlock the controversyTrends Endocrinol Metabolism. 2020;31(3):192-204. doi: 10.1016/j.tem.2019.11.011

  5. U.S. Food and Drug Administration. Hetlioz.

  6. Watanabe A, Hirose M, Arakawa C, Iwata N, Kitajima T. A case of non-24-hour sleep-wake rhythm disorder treated with a low dose of ramelteon and behavioral educationJ Clin Sleep Med. 2018;14(07):1265-1267.

By Brandon Peters, MD
Brandon Peters, MD, is a board-certified neurologist and sleep medicine specialist.