Meet DORA, the Latest Drug Class to Take On Insomnia

In February, a new insomnia drug, daridorexant (brand name: Quviviq) was approved by the Committee for Medicinal Products for Human Use of the European Medicines Agency for the treatment of insomnia.¹

This follows the U.S. Food and Drug Administration (FDA) approval of daridorexant for the treatment of insomnia in adults last January.²

What are dual orexin receptor antagonist (DORA) drugs?

Daridorexant, which belongs to the dual orexin receptor antagonist (DORA) drug class, has been shown to help induce sleep and maintain longer periods of sleep, resulting in improved daytime performance and function. Its chief side effects are mild, mostly headache and sleepiness.^3,4

The FDA has approved 2 other DORA drugs previously: suvorexant (Belsomra) first, in 2014, and lemborexant (Dayvigo) in 2019.^5,6

What are DORA drugs and how do they differ from other popular insomnia therapies?

How do DORA drugs work?

Other types of insomnia medications work to encourage sleepiness through a variety of mechanisms.

This is especially true for those drugs known as nonbenzodiazepine receptor agonists, or the “Z” drugs: eszopiclone, zaleplon, and zolpidem. You may be more familiar with the common brand, Ambien. However, these drugs have a wide variety of negative side effects, such as lingering headache and drowsiness (the “Ambien hangover”), nightmares, memory issues, dizziness, nausea, agitation, and more.⁷

Dual orexin receptor antagonist (DORA) drugs work differently. They bind with certain receptors to reverse orexin activity. Orexin (sometimes called hypocretin) is the substance in the brain that regulates arousal, wakefulness, and appetite. By reversing the over-activity of orexins in some people with insomnia, DORAs may help them achieve sleep once again by shutting down their drive to stay awake.

Fewer side effects

One of the greatest appeals to using DORA drugs to treat insomnia relates to side effects. Insomnia drugs like Ambien (zolpidem) carry significant risks for falling and cognitive decline in older adults. Meanwhile, DORA drugs exhibit far fewer side effects across all age groups, but especially in older people.⁸

The effects of the COVID-19 pandemic

The pandemic had brought with it increased rates for insomnia in the last couple of years, making it clear that people are needing more and better options for treating their sleeplessness. Before 2020, slightly more than a third of the population experienced problems with initiating sleep, maintaining sleep, and waking too early. Those rates increased to more than half the population by the end of 2020, and the use of sleep medication to battle insomnia also increased.⁹

This “COVID-somnia” trend has encouraged the emergence of new virtual CBT-i services to the forefront in place of face-to-face treatment, and the outcome has been largely positive.

CBT-i, the gold standard treatment, doesn't work for everyone

Cognitive behavioral therapy for insomnia (CBT-i) is a non-drug therapy touted by sleep specialists as the gold standard treatment for chronic sleeplessness. It’s considered highly effective and promises good long-term results.

For some, these services have been a lifesaver. But like many therapies, CBT-i doesn’t work for everyone. Or, it may only work in conjunction with a sleep drug like Ambien (or, now, one of the DORA drugs).

As the pandemic lingers, it’s critical that doctors have access to more and better options for treating chronic insomnia, like DORA drugs, so their patients can get the critical sleep they need.