Dual orexin receptor antagonists (DORAs) are a newer class of insomnia medications. They work by blocking signals in the brain that stimulate wakefulness.

DORAs may offer an alternative to people who live with insomnia and don’t want to take potentially habit-forming medication. Clinical trials and research studies have shown that DORAs are potentially very effective at helping people fall asleep faster and stay asleep.

DORAs are oral medications you take right before bed. They block chemicals in the brain that help you stay awake. This may reduce wakefulness and help you fall asleep.

There are currently three DORAs approved by the FDA for insomnia:

  • daridorexant (Quviviq)
  • lemborexant (Dayvigo)
  • suvorexant (Belsomra)

Suvorexant was the first DORA approved by the FDA in August 2014. Lemborexant is a newer drug that received approval in December 2019. Dariodorexant is the newest of the three and received FDA approval in January 2022.

Orexins are kinds of neuropeptides, chemical messengers in the brain. There are two distinct types: orexin A and orexin B. Each binds to specific receptors (OX1R or OX2R) critical to the sleep-wake cycle.

This means orexins are part of the brain’s mechanism that keeps you awake. DORAs stop orexins from binding with OX1R and OX2R receptors, so your body doesn’t get the same signal to wake up and move between stages of sleep. They can help improve your sleep.

DORAs are called dual orexin receptor antagonists because they work on both receptor types (OX1R and OX2R). Researchers are also investigating the use of drugs that work on only select orexin receptors for conditions such as major depressive disorder. These are called selective orexin receptor antagonists (SORAs).

Other medications for insomnia work differently to encourage sleep:

  • Benzodiazepines and Z-drugs work on brain signaling to create hypnotic, sedative, and muscle-relaxing effects.
  • Melatonin receptor agonists help create a manageable circadian rhythm or sleep-wake cycle.
  • Many over-the-counter (OTC) sleep aids contain diphenhydramine, which produces drowsy effects.

DORAs, instead of making you want to fall asleep or resetting your biological clock, prevent you from feeling awake. They’re the only insomnia medications that block the action of orexins.

Clinical trials and research studies appear to show DORAs can be effective in some people.

A 2017 study of 291 participants with a clinical diagnosis of insomnia found lemborexant helped people get to sleep faster and sleep longer than a placebo. The trial was performed over 2 weeks. The makers of lemborexant funded it.

A 2019 study of 1006 participants over 55 with insomnia found that lemborexant was more effective at delaying the time it gets to sleep and encouraging longer sleep than placebo or zolpidem (Ambien). The trial period was for 30 days. The makers of lemborexant funded this trial.

A 2017 meta-analysis of studies investigating suvorexant found that the drug improved people’s perception of total sleep time, sleep quality, and time to sleep onset. The authors concluded suvorexant had apparent effectiveness but also recommended comparative studies.

A 2020 meta-analysis comparing lemborexant and suvorexant found both drugs worked better than placebo on primary sleep measures, although lemborexant had a bigger effect compared to placebo than did suvorexant.

A 2020 clinical trial of 359 participants under 65 with insomnia found that daridorexant reduced wake time after sleep onset. The effectiveness of the medication depended on the dose the participants received. The trial was sponsored by the makers of daridorexant.

A 2020 clinical trial involving 58 participants over 65 with insomnia found that daridorexant improved wake after sleep onset and the time it took to achieve sleep, particularly at doses greater than 10mg. The trial was sponsored by the makers of daridorexant.

A 2023 review of research found that DORAs were more effective than a placebo at treating insomnia. A 10 mg dose of lemborexant resulted in the largest reduction in wake time after falling asleep, while suvorexant resulted in the largest long-term decrease.

DORAs appear to work for people with insomnia. In addition, they may have some benefits over other medications for insomnia.

Specifically, DORAs don’t seem to cause tolerance or withdrawal symptoms, unlike some other prescription sleep aids. They also don’t seem to cause rebound insomnia if someone stops taking the medication.

In general, DORAs are considered safe. But they do come with risks and potential side effects.

DORAs may cause daytime drowsiness the next day, especially if you can’t get a full night’s sleep.

People with narcolepsy should not take DORAs because they can increase daytime sleepiness. Part of the mechanism of narcolepsy is impaired orexin signaling, which DORAs can make worse for these individuals. DORAs can also increase the risk of cataplexy (muscle weakness often triggered by strong emotion) in people with narcolepsy.

Other potential side effects include:

You should talk with a doctor if you experience:

  • worsening depression or suicidal ideation
  • sleep paralysis
  • hallucinations
  • cataplexy
  • complex sleep behaviors (e.g., sleepwalking)

Let the doctor who prescribed the medication know about any other medications or supplements you’re taking to avoid potential interactions.

What medications are DORAs?

Dual orexin receptor antagonists (DORAs) block signals in the brain that stimulate wakefulness. There are three FDA-approved DORAs. They include: daridorexant (Quviviq), lemborexant (Dayvigo), and suvorexant (Belsomra).

What are the side effects of DORAs?

Side effects of DORAs can vary by individual. Common ones include daytime sleepiness, headache, and dizziness.

Is Ambien a DORA?

Zolpidem (Ambien) is not a DORA medication. It is in the sedative-hypnotic class. It works by causing a feeling of calm and can help you fall asleep. DORAs work by blocking signals in the brain that stimulate wakefulness.

DORAs work on brain signaling that encourages wakefulness. By turning off this signaling temporarily, these drugs help people to get better and longer sleep.

DORAs come with some side effects but appear to be non-habit-forming and a potential option for people with insomnia.