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Belsomra Mechanism of Action—Uncovering How Belsomra Helps You Sleep

Belsomra Mechanism of Action—Uncovering How Belsomra Helps You Sleep

Some nights are more difficult than others, leaving you restless and longing for some reinvigorating shut-eye. There are many sleep aids and techniques that people swear by, but even those can sometimes fail you. The next day is usually even worse, as the fatigue and brain fog can hamper your ability to perform everyday tasks.

With medications like Belsomra, you may be able to avoid such scenarios. Belsomra can help you fall asleep and rest uninterruptedly throughout the night.

How does it achieve that? That’s what this article aims to explain. Learn about Belsomra’s mechanism of action and what the clinical trials revealed about this medication.

What Is Belsomra?

Belsomra (suvorexant) is a sleep medication developed by Merck & Co. It was the first dual orexin receptor antagonist (DORA) approved by the Food and Drug Administration (FDA).

Belsomra is prescribed to individuals with:

  1. Sleep onset insomnia (difficulty falling asleep)
  2. Sleep maintenance insomnia (difficulty remaining asleep during the night)

The drug comes as an oral tablet in four doses. It should be taken 30 minutes before going to sleep, but only if you know you can sleep for at least seven hours before you have to wake up. Belsomra’s most common side effect is drowsiness, and it can affect cognitive and motor functions.

Here’s some basic information on Belsomra:



Active substance


Class of drug

Dual orexin receptor antagonist (DORA)

FDA approval



Merck & Co.

Controlled substance

Yes, Schedule IV 



Generic versions

None, brand-name only

Available dosages

5 mg, 10 mg, 15 mg, 20 mg

Suitable for children


Suitable for pregnant and breastfeeding women

Category C (risks can not be ruled out)



Belsomra Mechanism of Action

Belsomra’s mechanism of action is distinct from that of common sleep medications like Ambien. Belsomra doesn't interact strongly with acetylcholine, dopamine, GABA, or serotonin.

Instead, it blocks orexins A and B (neurotransmitters that regulate the sleep-wake cycle and promote wakefulness) from binding to receptors OX1R and OX2R, suppressing the wake drive. What this means for you is that after taking Belsomra, you may be able to fall asleep quicker and remain asleep for longer.

Belsomra’s orexin-blocking actions are associated with narcolepsy and cataplexy-like symptoms like daytime sleepiness and muscle weakness. Patients with narcolepsy and cataplexy should thus avoid using this medication.

Unlike certain antidepressants, Belsomra doesn’t significantly prolong the QTc interval, the time it takes for the heart to recharge between beats. Therefore, the risk of causing heart rhythm abnormalities is low.

Source: cottonbro studio

Belsomra’s Pharmacokinetics

The following table explains how the body interacts with Belsomra:


  • Belsomra should start working soon after you take your dose

  • If the drug is taken during or right after a meal, especially a high-fat one, it may take about an hour and a half longer for noticeable effects

  • You will feel the full effect about two hours after taking the medicine


  • Suvorexant distributes throughout the body with a mean volume of 49 liters

  • It binds to human plasma proteins and doesn’t accumulate in red blood cells


  • Belsomra is metabolized in the liver, particularly by the enzymes CYP3A and CYP2C19 (to a smaller extent)

  • The remaining substances are suvorexant and its metabolite hydroxy-suvorexant, which is pharmacologically inactive


  • The main excretion method is through the feces

  • The mean half-life (the time it takes the body to eliminate half the dose) is 12 hours, but it can vary based on age, medical conditions, and several other factors

  • Typically, suvorexant is no longer present in the body within three days

What Did Clinical Trials Reveal About Belsomra’s Efficacy?

Belsomra’s effectiveness in treating insomnia has been demonstrated in the three clinical trials preceding approval, which had nearly 2,000 participants in total. The first two were three-month efficacy trials, whereas the third one was a one-year crossover study using higher doses. In all three trials, Belsomra was superior to placebo in helping the patients both fall asleep and stay asleep.

In another study, the participant group that took Belsomra fell asleep about ten minutes faster than the control group that took the placebo. The Belsomra group also remained asleep for 31 minutes longer.

Still, everyone reacts to the substance differently. The doctor usually advises the patient to take Belsomra for a few days to a week to assess its effectiveness. If the dose doesn’t produce the desired results but also doesn’t cause significant side effects, the doctor may increase it. In case the patient’s insomnia stagnates or worsens after seven to ten days, there could be an underlying cause requiring a different treatment.

Source: Vladislav Muslakov

What Did Clinical Trials Reveal About Belsomra’s Safety?

In Belsomra clinical trials, the most commonly reported side effect was drowsiness. Less frequent adverse reactions were:

  1. Headache
  2. Dizziness
  3. Unusual dreams
  4. Diarrhea
  5. Respiratory problems

Studies also showed that various factors can influence Belsomra’s effect. High doses entailed similar side effects to low doses, but they appeared more frequently. The concentration of suvorexant in blood was higher in women and obese patients. They also experienced side effects more frequently than their opposing groups.

The side effect profiles in elderly and non-elderly patients were consistent. Still, older patients are at a higher risk of falling and injury, so caution is necessary during treatment.

Patients with the following conditions are at risk of developing severe adverse reactions to Belsomra and shouldn’t use the medication:

  • Narcolepsy and cataplexy
  • Breathing problems
  • Severe liver problems
  • Depression
  • Substance abuse problem

Belsomra can interact with some medications, including other CNS depressants, CYP3A inhibitors or inducers, antiepileptics, antihistamines, and antibiotics. It may also interact with supplements and herbs such as St. John’s wort and valerian, as well as alcohol and cannabis.

Belsomra carries a Category C pregnancy warning, so risks can’t be ruled out. The available data is insufficient to determine whether it’s safe for use in pregnant and breastfeeding women, but animal studies indicate potential negative effects. This drug is also not suitable for children.

Belsomra Tolerance and Abuse Potential

The Drug Enforcement Administration (DEA) labels Belsomra as a Schedule IV controlled substance with low potential for dependence and misuse.

In the clinical trials, there was no evidence of physical dependence or tolerance after long-term Belsomra use. No withdrawal symptoms were reported after discontinuation of Belsomra either.

Those with past or ongoing substance abuse issues should still be careful, as Belsomra may lead to psychological dependence.

Source: Emma Filer

Other Sleep Solutions To Consider

Belsomra is a prescription-only sleep medication. To get access to it, you must visit a healthcare professional, such as a primary care doctor, psychiatrist, or sleep medicine specialist. You should inform them of any medical conditions you have and medications or supplements you take. Based on this information, the doctor will evaluate whether you’re a good candidate for Belsomra and, if so, decide on the dosage.

In case they determine Belsomra is not suitable for you, they may prescribe another medication, such as:

  • Quviviq (daridorexant)
  • Dayvigo (lemborexant)
  • Ambien (zolpidem)
  • Lunesta (eszopiclone)
  • Sonata (zaleplon)
  • Trazodone
  • Vistaril (hydroxyzine pamoate)
  • Lorazepam
  • Xanax (alprazolam)

They may also suggest getting an over-the-counter sleep aid like Benadryl, Tylenol, ZzzQuil, Unisom, and melatonin.

Oftentimes, medication alone is not enough to bring about lasting improvements in overcoming sleep issues. Ideally, you should undergo cognitive behavioral therapy for insomnia (CBT-I), make lifestyle changes, and form healthy sleeping habits. Considering the scarcity of sleep-trained doctors skilled in creating an effective treatment, taking a holistic approach may not be easy—but telehealth solutions like Kick can help you get a good night's sleep conveniently.

Source: 100 files

Kick—Sleep Science at Your Fingertips

Kick is an online performance medicine clinic that makes sleep medicine accessible. Instead of having to visit a doctor in person, you can complete a short survey online and connect with one of our sleep experts in one day.

Our doctor will prescribe two trial sleep medications, which can be delivered to your door or the local pharmacy. Kick’s medication selection includes fast-acting yet effective options such as:

  • Gabapentin (nerve medication)
  • Trazodone (antidepressant)
  • Cyclobenzaprine (muscle relaxant)
  • Hydroxyzine (antihistamine)
  • Ramelteon (melatonin antagonist)

After trying your prescriptions for one week each, you’ll give your feedback to the doctor. They’ll fine-tune the treatment until you achieve optimal results. With more than one medication on hand, you can rotate them to avoid dependence.

Besides medications, our sleep doctor will provide CBT-I coaching and useful advice on sleep hygiene. They’ll also stay in touch, checking in regularly to ensure the treatment is working for you.

Choose Kick and Celebrate Your Mornings

Designed by a prominent Stanford sleep expert, Kick's sleep program earns high praise from patients, as evidenced in raving Trustpilot reviews.

“Absolutely Amazing

Kick has been amazing during a difficult time. I can’t recommend them enough, their service and care has been excellent throughout the entire process. I am truly thankful for the service they are providing.”

Blake, U.S.

To try Kick’s sleep program, follow these three simple steps:

  1. Sign up and start the 15-minute sleep visit
  2. Complete the questionnaire to provide information about your sleep issue and medical history
  3. Enter the shipping and payment details

Kick's sleep program will set you back $129 a month—$99 for the monthly subscription and $30 for the medication and shipping. If the doctor determines Belsomra is not the solution for you, you won’t have to pay for the consultation as per our “Doctor Guarantee.”

Unlock better sleep today with Kick. Sign up and get personalized sleep treatment that will bring you peaceful nights and brighter days in no time.

Featured image source: Karolina Grabowska