The 7+ Benefits Of Suvorexant (Belsomra): A Dual Orexin Receptor Antagonist

Suvorexant (Belsomra): The First Approved DORA



Suvorexant is a dual-orexin receptor antagonist that improves insomnia. 


  1. Basics Of DORAs
  2. Benefits Of Suvorexant
  3. Caveats
  4. Dosage And Indications
  5. Mechanism Of Action
  6. Genetics
  7. More Research

Basics Of DORAs

There are different patterns of insomnia, such as a delayed onset of sleep and difficulty maintaining sleep. R

Orexins (also known as hypocretins) are neuropeptides which are involved in the regulation of sleep and arousal. R

Orexins A and B promote wakefulness. R

Blocking their receptors should therefore reduce wakefulness and promote sleep. R

Dual orexin receptor antagonists (DORAs) are a new class of insomnia medication that target wakefulness-promoting neuropeptides to regulate the sleep-wake cycle. R

Unlike GABAA receptor modulators, DORAs promote both non-rapid eye movement (NREM) and REM sleep, do not disrupt sleep stage-specific quantitative electroencephalogram spectral profiles, and allow somnolence indistinct from normal sleep. R

Suvorexant is the first DORA to be approved in the US, Japan, and Australia, and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. R

Another DORA is Lemborexant, which I will write about later. R

Benefits Of Suvorexant



1. Improves Sleep And Ameliorates Insomnia

One Month Use:

In a trial of suvorexant, patients with primary insomnia were randomised to take 10 mg, 20 mg, 40 mg or 80 mg for four weeks. R

At the start of the study, the average sleep efficiency was 66% with a total sleep time of 316 minutes. R

These measures improved from the first night of active treatment. R

After four weeks of taking suvorexant, sleep efficiency had improved by 4.7–10.4% and total sleep time had increased by 22–50 minutes. R

Three Month Use:

In two 3-month randomized controlled clinical trials, Suvorexant (at 40/30mg and 20/15mg) was superior to placebo. R

It improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated. R

One Year Use:

A one-year trial randomised 781 patients with primary insomnia to take suvorexant or a placebo. R

Patients over 65 years took 30 mg and other patients took 40 mg. R

At the start of the study, the patients in the placebo group said it was taking them 65 minutes to get to sleep and they slept for an average of 330 minutes. R

When efficacy was assessed over a month the suvorexant group was getting to sleep 18 minutes sooner on average and sleeping for 39 minutes longer than before and these benefits were maintained for the patients who continued treatment for one year. R

2. Improves Anxiety And Depression

In those with insomnia, suvorexant treatment can improve the severity of anxiety and depression from insomnia. R

3. May Help Schizophrenia Treatment

Suvorexant may be beneficial for short term (once monthly) use in those using antipsychotics. R

4. May Help Delirium Treatment

Suvorexant may be helpful in the treatment of elderly patients admitted for acute care may provide protection against delirium. R

5. May Help With Cocaine Abuse

Suvorexant may have some benefits  with Cocaine Abuse. R

For example, suvorexant attenuates motivational and hedonic properties of cocaine and may be useful in treating substance use disorders (by modulation of Dopamine). R

6. May Benefit Diabetes Treatment

Suvorexant may have some benefits in DiabetesR

In diabetic animal models, suvorexant improved impaired Glucose tolerance. R

7. May Help Alzheimer’s Disease Treatment

Suvorexant may help with treatment of insomnia in Alzheimer’s Disease (AD). R

For example, in a study evaluating insomnia with AD patients, all of patients that received Suvorexant were able to sleep continuously for 6 hours per night, with minimal side effects. R


Multiple clinical trials has shown Suvorexant to be generally safe. R R

Suvorexant is not recommended for patients with severe liver impairment. R

However, severe renal impairment has little effect on drug concentrations. R

Suvorexant should not be used with CYP43A inhibitors such as ciprofloxacin, clarithromycin, the azole antifungal drugs and grapefruit juice. R

Enzyme inducers such as phenytoin reduce the concentration of suvorexant. R

Rebound insomnia has occurred in patients that stopped suvorexant, but this was only statistically significant in one trial for patients stopping the 30 mg or 40 mg dose. R

Suvorexant is contraindicated in narcolepsy. R

They should therefore not drive or operate machinery if they are not fully alert. R

Alcohol and other drugs that depress the central nervous system should be avoided. R

The safety of suvorexant in pregnancy and lactation is unknown. R

Unconscious nighttime activity, sleep paralysis, hypnagogic hallucinations, mild cataplexy, and suicidal ideation have been seen with suvorexant use at higher doses. R

In clinical trials of suvorexant, somnolence occurred more frequently in female than male patients who received the 15 mg and 20 mg dose (8% for female patients versus 3% for male patients; no p value reported). R

Also more commonly reported in female patients with suvorexant use are headache, abnormal dreams, xerostomia, cough, and upper respiratory tract infection. R

Although rare, acute worsening of depression with emergence of suicidal thoughts have been reported with Suvorexant use. R

Dosage And Indications

Approved indication: insomnia R

Drug name: Belsomra (manufactured by Merck Sharp and Dohme) R

Dosage: 15 mg and 20 mg tablets R

Suvorexant is a schedule IV controlled substance based on its abuse potential, a determination made by the US Drug Enforcement Administration. R

How To Use:

The drug is taken
within 30 minutes of bedtime.

This should be at least seven hours before the patient plans to get up again.

Those with respiratory issues (such as Obstructive Sleep Apnea) should go on the lowest dose possible. R

Mechanism Of Action


  • Reduces Cortisol R
  • Reduces OX1R R
  • Reduces OX2R R
  • Reduces PEPCK R
  • Reduces PGC-1α R
  • Reduces WBC R


  • The maximum drug concentration (median peak plasma concentrations) is reached in 2 hours and not affected by food. R
  • Suvorexant has a volume of distribution of 105.9 L and is highly protein bound (99.5%). R
  • Suvorexant elimination occurs primarily through feces (66%) and less commonly through urine (23%). R
  • Its half-life is approximately 12.2 hours on average (range 8–19 hours) and steady-state plasma concentrations occur in about three days with daily administration. R
  • Metabolized by CYP4503A and with a minor contribution from CYP219, 1A2, and 2B6 resulting in the metabolite, hydroxyl suvorexant, which is therapeutically inactive. R R
  • Suvorexant works by selectively blocking the binding of neuropeptides orexin A and B to receptors OX1R and OX2R, suppressing wakefulness. R



See Hypocretin/Orexin Post (unfinished).

More Research

  • There is some basis to speculate that suvorexant might be safer than alternative hypnotics in terms of cancer, dementia, infections, and mortality. R