Dual orexin receptor agonists (DORAs) are a type of treatment for chronic insomnia. Studies have found that they may help people fall asleep, stay asleep, or both.

Insomnia is a common sleep disorder where a person has difficulty falling or staying asleep. Chronic insomnia is when these sleep problems occur at least three times per week for at least 3 months, and doctors cannot link them to another condition or medication. Chronic insomnia can limit a person’s ability to function during waking hours, reduce their quality of life, and increase their risk of falls and other accidents.

“Insomnia really affects their whole life, so it has to be taken very seriously,” Fariha Abbasi-Feinberg, M.D., F.A.A.S.M., F.A.A.N., told Medical News Today. Abbasi-Feinberg is the director of sleep medicine at Millennium Physician Group in Fort Myers, Florida. She is also a member of the American Academy of Sleep Medicine’s (AASM) board of directors.

The 2021 AASM guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for the condition. Some people also require medication to treat chronic insomnia.

DORAs are one type of medication for chronic insomnia. Read on to learn more about this treatment option.

A DORA is a type of sleep medication that blocks the effects of the neurotransmitter orexin.

Neurotransmitters are chemical messengers that carry signals from nerve cells. Multiple types of neurotransmitters help to regulate the body’s sleep-wake cycle.

“We have neurotransmitters that help keep us alert, and then we have neurotransmitters that help us fall asleep,” said Abbasi-Feinberg.

Orexin is a neurotransmitter that promotes wakefulness. DORAs bind to orexin receptor 1 and orexin receptor 2, blocking the effects of orexin, reducing wakefulness, and helping people sleep.

The Food and Drug Administration (FDA) has approved two types of DORA for treating chronic insomnia in adults: suvorexant (Belsomra) in 2014 and lemborexant (Dayvigo) in 2019. Scientists are also developing and testing other DORAs that they might put forward for approval in the future.

DORAs are the only type of medication for insomnia that blocks the effects of orexin.

Other medications for chronic insomnia include:

  • benzodiazepine receptor agonists, also known as Z-drugs, such as:
    • eszopiclone (Lunesta)
    • zaleplon (Sonata)
    • zolpidem (Ambien)
  • benzodiazepines, such as triazelem (Halcion) and temazepam (Restoril)
  • melatonin receptor agonists, including ramelteon (Rozerem)
  • histamine receptor agonists, including doxepin (Silenor)

Doctors also prescribe other medications off-label to treat insomnia, including some:

  • antidepressants
  • antipsychotics
  • antianxiety medications
  • antihypertensives

These medications affect the action of different neurotransmitters. Different people with insomnia may find that certain medications are more effective than others for treating the condition.

Multiple clinical trials suggest that DORAs have significant benefits for treating insomnia.

In 2014, researchers employed by the makers of Belsomra published the results of two phase 3 clinical trials on the drug. Both trials found that after 3 months of treatment, participants taking Belsomra woke less often in the night than those taking a placebo. They also reported getting more sleep overall.

In 2019, scientists employed by the creators of Dayvigo reported the results of a phase 3 clinical trial on the drug. This medication was more effective than a placebo for helping people fall asleep and stay asleep. It was also more effective than the sleep medication Ambien.

The authors of another phase 3 clinical trial on Dayvigo reported their initial results in 2020. The makers of Dayvigo employed the researchers. Participants who received Dayvigo reported falling asleep more quickly and waking less often than those who received a placebo. After 6 months of treatment with Dayvigo, participants’ total sleep time had increased by a reported average of 70–74 minutes per night.

The same research group published a follow-up report in 2021. Participants who continued to receive Dayvigo for 12 months reported ongoing benefits.

When the authors of a 2021 meta-analysis compared studies on Dayvigo with studies on Belsomra and 14 other insomnia medications, they found benefits associated with both DORAs. The creators of Dayvigo funded the study.

Dayvigo appeared to be the most consistently effective treatment for helping people fall asleep and increasing total sleep time. Belsomra appeared to be the most consistently effective treatment for helping people stay asleep. However, more studies are necessary to compare DORAs with other insomnia medications directly.

A doctor may prescribe a sleep medication such as a DORA when behavioral modifications alone are not enough to treat insomnia.

“Anyone with insomnia should start with good sleep hygiene, regular bed and wake times, technology off 1 hour before sleep, and a cool dark bedroom,” Dr. Alex Dimitriu, a psychiatrist, sleep medicine specialist, and the founder of Menlo Park Psychiatry & Sleep Medicine in California told MNT. “When insomnia persists despite efforts to improve sleep hygiene, it may be worth considering a sleep aid along with ongoing behavioral interventions.”

A doctor will consider a person’s medical history and treatment preferences when deciding which type of sleep medication to prescribe.

The American Geriatrics Society recommends that older adults avoid Z-drugs, benzodiazepines, and doxepin. Z-drugs and benzodiazepines increase the risk of confusion, falls, and other accidents. Doxepin can cause blood pressure to drop suddenly when a person sits or stands up.

Although more research is necessary, DORAs may provide a safer insomnia treatment for older adults. One 2020 study found that older adults taking Dayvigo had greater postural stability than those taking Ambien. This increased stability might reduce the risk of falls.

Clinical trials suggest that the risk of serious side effects from DORAs is low.

Like other sleep medications, DORAs can increase daytime sleepiness, which may interfere with a person’s ability to drive safely or complete other routine tasks.

“The most significant [risk] with DORAs is of next-day sedation, especially in the morning,” said Dimitriu. “Sleepy driving is always a concern for anyone using a sleep aid, especially if driving early.”

DORAs may not be a safe option for people with narcolepsy or excessive daytime sleepiness, Dimitriu advised.

DORAs may also interact with certain medications. Before taking a new medication, a person should let their doctor know about any medications and supplements they are already taking and ask about the risk of interactions.

People who have difficulty sleeping should let their doctor know and ask for a referral to a sleep specialist. Chronic insomnia can negatively affect their physical health and mental well-being. Getting treatment is important.

The first-line recommended treatment for insomnia is behavioral modifications with CBT-I. In some cases, medication is also necessary.

DORAs are a type of sleep medication that reduce wakefulness. Evidence suggests they may help people fall asleep, stay asleep, or both.

More research is necessary to learn how the potential benefits and risks of DORAs compare with those of other insomnia treatments.