Belsomra vs Ambien Verdict: Switch To Belsomra

Comparing Belsomra vs Ambien, bear in mind that:

  • Efficacy. Belsomra is probably less effective than Ambien but does modestly improve sleep duration and quality
  • Side effects. Ambien (but not Belsomra) is associated with an increased risk of Alzheimer’s disease and early mortality
  • FDA approval. Belsomra is a much newer drug: it was approved by the FDA in 2014 whereas Ambien was approved in 1992 - Patients who are particularly concerned about the adverse effects of chronic Ambien use on memory and cognition may wish to use an alternative like Belsomra
  • Physician outlook. Some physicians advise against trialing new drugs until several years of long-term Phase IV monitoring has allowed more experience with the benefits and adverse effects
  • Duration. Belsomra lasts much longer: it has a half-life of 10 hours vs  2 hours for Ambien
  • Hangover. Belsomra is associated with next-day grogginess due to its longer elimination half-life

To alleviate insomnia, I personally use a combination of magnesium, l-theanine, melatonin, and lavender for sleep. All of these substances are mildly sleep-promoting, but together they pack a punch.

Further reading: The Sleep Optimization Checklist

Belsomra vs Ambien: Belsomra Is (Probably) Safer but Less Effective

Consumer Reports points out that:

…the Belsomra group slept only 16 minutes longer—6 hours and 12 minutes total vs. 5 hours and 56 minutes for the placebo group.

Consumer reports is right: Belsomra only modestly improves sleep efficiency and sleep latency.

Sleep latency refers to the amount of time it takes to follow asleep; sleep efficiency is the amount of time you spend sleeping divided by the total time you spend in bed. Ideally, sleep efficiency would be 100%, which would mean you’d fall asleep the moment your head hits the pillow.

Compared to Ambien, Belsomra is less effective. It probably works for 1/3 of patients presenting with a complaint of insomnia. However, if Belsomra does help alleviate your insomnia, then it’s a better long-term option than Ambien, which can negatively impact brain function (over the long term).

I would personally prefer to take Belsomra along with melatonin and use other strategies to help treat insomnia. That’s because z-drugs and benzodiazepines are associated with an increased risk of cognitive decline.

But some patients absolutely need Ambien to sleep and should not be deterred from using it if it effective for them.

Belsomra’s long half-life (10 hours) is a double-edged sword. On the one hand, it explains why Belsomra improves sleep maintenance (e.g., by decreasing the frequency of early-morning awakenings).

On the other hand, Belsomra is associated with next-day grogginess since the drug takes longer to eliminate. But Belsomra’s next-day grogginess is nowhere near as bad as the hangover induced by antihistamine sleep aids like hydroxyzine or diphenhydramine because these antihistamines can take over 24 hours to metabolize and excrete.

Other sleep aids besides Belsomra or Ambien:

  • Ramelteon (Rozerem) – a melatonin-like drug
  • Hydroxyzine – a benign antihistamine with no anticholinergic activity
  • A sedating antidepressant (e.g., low-dose mirtazapine or a low-dose tricyclic)
  • Nutraceuticals with sleep-promoting properties like l-theanine

The important difference Belsomra vs Ambien in terms of pharmacology is that Belsomra targets in the orexin system, whereas Ambien affects GABA (in a manner analogous to Benzodiazepines).

Further reading from the NIH: Comparing Newer Drugs for Insomnia

About Ambien

Ambien (aka Zolpidem) is a "z-drug", a nonbenzodiazepine hypnotic used to help with sleep initiation. Ambien is habit-forming, and is notoriously linked to bizarre behavior like sleep eating, sleep sex, and a general state of intoxication/disinhibition (if one stays awake after ingestion). 

The FDA has called for lower doses of Ambien due to safety concerns:

FDA recommends that the bedtime dose be lowered because new data show that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving.

That being said, millions of Americans take Ambien every night without any obvious changes in behavior or personality.

Ambien Is A Weird Drug

To be frank, Ambien is a pretty weird drug. For example, administration of Ambien to some coma patients will paradoxically rouse them from unconsciousness. How a central nervous system (CNS) depressant like Ambien would allow a patient to temporarily regain consciousness remains mysterious.

Ambien is a pretty effective sleep aid. Its major disadvantage is that long-term use is linked to amnesia and cognitive impairment that does not always resolve after you stop taking the drug. This puts the Belsomra vs Ambien comparison into perspective, because Belsomra does not have this abuse liability.

Belsomra vs Ambien: What’s the Difference?

Merck Senior Director of Neurosymptomatic Disorders

Belsomra is a relatively new sleep aid that was approved by the FDA in 2014, whereas Ambien has been around for over a decade.

Belsomra has a pretty novel mechanism of action. It affects (specifically, blocks) orexin receptors. Orexin is an endogenous wakefulness-promoting peptide in the brain that helps keep us alert throughout the day.

Belsomra is an orexin receptor antagonist, that is, it blocks the activity of this peptide, orexin, preventing it from binding to its receptor. Orexin receptor blockade has a sleep promoting effect; narcolepsy (sleeping too much) is thought to arise from impaired orexin signaling.

Crudely speaking, taking Belsomra turns you into a narcoleptic for one night.

Ambien, by contrast, works by increasing the activity of GABA receptors in the brain. Increasing GABA receptor activity decreases neuronal excitability and promotes sleep.

Belsomra's mechanism of action (orexin antagonist), has a distinct advantage over Ambien’s (GABA receptor modulator). Drugs that affect GABA receptors (benzodiazepines and others) are associated with a host of nasty effects, like abuse and dependence, protracted withdrawal syndromes, anxiety disorders, mild cognitive impairment and an increased risk of Alzheimer’s disease. That being said, the short-term use of Ambien to help with problems sleeping is unlikely to do any harm.

When comparing Belsomra vs Ambien, it is important to recognize that Belsomra has this important advantage: it is a more selective agent with a more favorable side effect profile and is not a substance of abuse.

Belsomra is unlikely to result in the same kind of withdrawal syndrome you might get from prolonged Ambien dependence. Rapid withdrawal from chronic, high-dose Ambien use can result in seizures, for example.

Belsomra also alters electrical activity in the brain to a lesser extent compared with other sleep medications like Ambien, Trazodone and others. This means that Belsomra may help alleviate insomnia without compromising sleep architecture.

Should You Switch To Belsomra?

There are some good reasons to switch from a benzodiazepine or z-drug sleep aid like Ambien to Belsomra. The most important reason is that Belsomra is likely less hard on your brain and is a more viable long-term strategy.

However, comparing Belsomra vs Ambien, recall that Belsomra has one important disadvantage. It is less effective, and will only be helpful for a smaller subset of people with insomnia compared to Ambien.

This makes sense- Belsomra is a more selective agent, which promotes sleep by blocking orexin receptors. Ambien and other z-drugs globally depress brain activity in a manner reminiscent of anesthetics, ethanol and benzodiazepines. This results in more robust sleep-promoting/hypnotic effects of Ambien vs Belsomra.

I’m not a doctor and not qualified to provide medical advice, but if I was deciding between Belsomra vs Ambien, your best bet would be to use Belsomra as a first-line agent in the management of insomnia, and if that fails move to stronger hypnotics, like Ambien.

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Xavier Kent

I'm interested in nutrition, nootropics, and javascript. I'm a firm believer in getting really good at one thing.


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