Dual orexin receptor antagonists (DORA) for insomnia

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

Insomnia is a common sleep disorder that causes a person to have difficulty falling or staying asleep. Chronic insomnia is when these sleep problems occur at least three times a week for at least 3 months and doctors cannot associate them with any other medical condition or drug. Chronic insomnia can impair a person’s wakefulness, decrease their quality of life, and increase the risk of falls and other accidents.

“Insomnia really affects your whole life, so it needs to be taken very seriously,” Fariha Abbasi-Feinberg, MD, FAASM, FAAN, told Medical News Today. Abbasi-Feinberg is the director of sleep medicine for the Millennium Physician Group in Fort Myers, Florida. She is also a member of the Board of Directors of the American Academy of Sleep Medicine (AASM).

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

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

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

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

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

Orexin is a neurotransmitter that promotes wakefulness. DORAs bind to orexin receptor 1 and orexin receptor 2, block the effects of orexin, reduce wakefulness and help sleep.

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

DORAs are the only insomnia drugs that block orexin from working.

Other drugs 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 drugs off-label to treat insomnia, including some:

  • Antidepressants
  • Antipsychotics
  • Anti-anxiety medication
  • antihypertensive agents

These drugs affect the effects of various neurotransmitters. Different people with insomnia may find that certain drugs are more effective than others in treating the condition.

Several clinical studies suggest that DORAs have significant benefits in treating insomnia.

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

In 2019, scientists from the developers of Dayvigo reported the results of a phase 3 clinical trial with the drug. This drug was more effective than a placebo at helping people fall asleep and stay asleep. It was also more effective than the sleeping pill Ambien.

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

The same research group published a follow-up report in 2021. Participants who received Dayvigo for 12 months reported lasting benefits.

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

Dayvigo appeared to be consistently the most effective treatment at helping people fall asleep and increasing the overall time they sleep. Belsomra seemed consistently the most effective treatment at helping people fall asleep. However, more studies are needed to directly compare DORAs with other insomnia drugs.

A doctor may prescribe a sleep aid such as DORA if behavior changes alone are not enough to treat insomnia.

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

A doctor will consider a person’s medical history and treatment preferences when deciding what type of sleep aids 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 a sudden drop in blood pressure when a person is sitting or standing up.

Although more research is needed, DORAs may provide safer treatments for insomnia for older adults. A 2020 study found that older adults who took Dayvigo had greater postural stability than those who took Ambien. This increased stability can reduce the risk of falls.

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

Like other sleep aids, DORAs can increase daytime sleepiness, which can affect a person’s ability to drive safely or perform other routine tasks.

“The most important [risk] with DORAs, sedation is the next day, especially in the morning, ”said Dimitriu. “Sleepy driving is always a problem for anyone who uses a sleep aid, especially when driving early.”

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

DORAs can also interact with certain drugs. Before taking a new medication, a person should tell their doctor about all medications and they are already taking and ask about the risk of interactions.

People with insomnia should inform their doctor and ask for a referral to a sleep specialist. Chronic insomnia can have a negative impact on your physical health and mental wellbeing. Treatment is important.

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

DORAs are a type of sleep aid that reduces wakefulness. There is some evidence that it can help people fall asleep, stay asleep, or both.

More research is needed to find out how the potential benefits and risks of DORAs compare to other treatments for insomnia.

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