Sleep deprivation is an enormous issue for Americans. The CDC suggests 1 in 3 Americans don’t sleep enough.
According to the American Sleep Association:
- Almost 70 million U.S citizens have a sleeping disorder
- Insomnia is the most common sleep disorder, and around 30% of adults suffer from insomnia in the U.S
- Approximately 10% of Americans suffer from long-lasting insomnia
- Around 5% of Americans report falling asleep when driving
- Nearly 40% of people suggest they suffer from daytime sleepiness
Unfortunately, sleep apnea and other sleep disorders can wreak havoc on mental and physical health. So we need as many tools to improve sleet outcomes. However, Daridorexant, a dual orexin receptor antagonist approved by the FDA in January 2022, can improve sleep outcomes.
Scientists found 25mg or 50mg doses of Daridorexan increased sleep outcomes. In addition, the 50mg dose significantly reduces daytime sleepiness, according to Emmanuel Mignot, the MD of the Stanford Center for Sleep Research.
The researchers wrote, “Improvements in sleep variables were achieved without excess sleepiness the following morning, and improvements in daytime functioning were observed,”
“The improvement in sleep perceived by participants in these studies was consistent with that objectively measured by polysomnography.”
The Studies: Daridorexant 50mg and 25mg Vs Placebo
Researchers conducted two scientific studies on Daridorexant. In Study 1, 930 participants were randomized between June 2018 and February 2020 to daridorexant 50 mg (n=310), daridorexant 25 mg (n=310), or placebo (n=310). In Study 2, 924 people were randomized between May 2018 and May 2020 to daridorexant 25 mg (n=309), daridorexant 10 mg (n=307), or placebo (n=308).
Most participants in the two studies were female: 67% in Study 1 and 69% in Study 2. Furthermore, in each study, 39% of participants were aged 65 or over. Approximately 89% of participants were white, and 8% were African American or black.
In comparison to Placebo, daridorexant 50 mg and 25 mg improved outcomes at months 1 and 3 said Emmanuel Mignot. What’s more, researchers saw the most considerable effect with the highest dose (50mg) tested in trials, shortly followed by the 25mg dose. However, researchers found the 10mg dose didn’t have a significant effect. Here is a comprehensive breakdown of the two studies:
During study 1, participants in the daridorexant 50mg group at month 1 compared with placebo at month 1 witnessed reduced levels of WASO and LPS. Researchers found a difference of -22.8 min for WASO and -11.4 min for LPS. During the third month, researchers found the average difference for WASO was -18.3 min and -11.7 min for LPS.
The daridorexant 50mg group improved their self-reported sleep time versus placebo at month 1, with an average difference of 21.1 min in month 1 and 19.8 min in month 3. Additionally, on the IDSIQ, researchers found improved sleepiness domain scores in the 50mg group at month 1 (average difference -1.8) and month 3 (average difference -1.19.)
Study 1 also showed reduced levels of WASO and LPS in the 25mg group at month 1 versus placebo, with an average reduction of -12.2 min in WASO and -8.3 min in LPS. At month 3, study 1 showed the difference in WASO was -11.9 min and -7.6 min in LPS. Finally, the 25mg group witnessed significantly improved self-reported total sleep time, with an average difference of 12.6 min in month 1 and 9.9 min in month 3 over placebo.
During Study 2, researchers found that daridorexant reduced WASO among participants in the 25mg group versus placebo with an average difference of -11.6 min at month 1 and -10.3 min at month 3. However, Study 2 didn’t show any significant differences in LPS during month 1 or month 3 for the 25mg group.
Study 2 found the 25mg had improved self-reported sleep time at month 1 (average difference of 16.1 min) and month 3 (average difference 19.1 min.) However, the 10mg group didn’t show any differences in self-reported sleep time or IDSIQ sleepiness domain scores at 1 or 3 months versus the placebo group. During both studies, the commonness of adverse side effects was consistent among adults under 65 years old. The most common symptoms were headaches and nasopharyngitis.
An Overview of the Studies
Although the studies on daridorexant were positive, some researchers argued there are other ways to cure insomnia. According to the guidelines of the American College of Physicians and the European Sleep Research Society, the first treatment option for insomnia is cognitive behavioral therapy for insomnia (CBT-I). Kai Spiegelhalder, Ph.D., of the University of Freiburg in Germany said, “This treatment is safe and effective but not widely available.”
Although the studies provide evidence that daridorexant is a viable treatment for insomnia, future studies are essential. The editorialists said, “future studies should provide essential data not only on long-term effects but also on the effects on patient-centered outcomes that are directly related to the core symptoms of insomnia. More work is also needed to establish how daridorexant will fit within current treatment pathways — e.g., after non-response to CBT-I,”
They also wrote, “daridorexant out-performed placebo by less than 2 points on the Insomnia Severity Index in both reported trials, questioning the clinical importance of the study findings from the patients’ perspective.”
Limitations of the Studies
Although the studies prove that daridorexant is effective, there are various limitations. The most significant limitation was the researchers conducted the study on predominantly white people with moderate to severe insomnia. The authors suggested a broader study group would provide better generalizations.
In addition, the researchers noted that the IDSIQ instrument is novel and used prospectively for the first time in these studies. They added, “Therefore, the effects of daridorexant observed with IDSIQ cannot be benchmarked with those of any other therapeutic intervention.” The FDA approved the 25mg and 50mg dose of daridorexant. However, the FDA recommended the United States classify daridorexant as a controlled substance.
Daridorexant looks highly promising. The studies showed better results than placebo. However, researchers suggest they need to test daridorexant more to have a more precise understanding of its usefulness. Still, it’s positive news for the millions of people battling insomnia
Sources and Credits:
Paul Smyth, MD, BreakingMED™
The Lancet Neurology