How Does Hetlioz Compare to Melatonin to Treat Non-24?


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 of the body’s own biological clock, or circadian rhythm. It fails to align with the 24-hour day, a condition commonly seen in blind people but sometimes in other groups too.

Hetlioz (tasimelteon) is a drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of non-24 in adults, and more recently for the genetic Smith-Magenis Syndrome (SMS). It was approved based on placebo-controlled trials in both cases. It acts on brain receptors for the hormone melatonin and was more effective for treating non-24 than placebo pills.

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


Standard Care for Non-24 Treatment

In its guideline update from 2015, published just after the availability of Hetlioz, the American Academy of Sleep Medicine (AASM) continues its call to use melatonin for treating non-24. It 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 the prescribed Hetlioz drug does.

Because melatonin is not an FDA-approved drug, it is important to be sure of the quality and precise contents of the product. Many supplements have 10 times the melatonin needed for non-24, or even more. This may flood the body’s system, limiting benefits and leading to side effects.

Some of these melatonin side effects include:

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

When comparing the possible side effects, headaches and drowsiness may be seen when using 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 them, and problems may come back if a dose is missed. A sleep specialist may be able to help you decide between using melatonin or Hetlioz, and help you to know the doses and timing are right.


Melatonin supplements have long been used to treat non-24 sleep disorders, and the drug Hetlioz was approved by the FDA in 2014. Yet there are still no clinical research trials comparing both to see which works better, or what risks come with taking them. As such, what is “best” will be a decision for you and your doctor.

Assessing the Treatment Effects

How do you know if the treatment is working? Most people with non-24 have cycles of insomnia and daytime sleepiness. It makes it hard to function on a typical schedule. These 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.

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.

For right now, people who have non-24 challenges, whether because of vision or a genetic cause, have a chance to get their bodies—and their lives—back on track using either melatonin and Hetlioz.

But there are real differences, and it’s a good idea to know the benefits and risks of both products.

A Word From Get Meds Info

Hopefully, further research will make direct comparisons between Hetlioz and melatonin. 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 doctor more information to make the best possible choices.

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