The Newest Sleep Aids and How They Work

Health Professional
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If you struggle with insomnia on a chronic basis, then it’s likely you have taken an over-the-counter sleep aid, or been prescribed a sleep medication.

How do traditional sleep aides work?

Traditional sleep aides and tranquilizers work by binding to areas in the nervous system known collectively as the GABA complex (Gamma Amino Butyric Acid).   Since the discovery of this sleep mechanism, more has been learned with regards to the many other potential sites that play a role in sleep.  Newer medications that bind to these different sites have been developed, all with different effects on the nervous system.

Sleep aids that target the GABA complex

The most well known agent that targets the GABA complex is Diazepam (Valium), which was the most often prescribed drug in this group of drugs known collectively as Benzodiazepines “Benzos.” The drugs in this group bind to different sites within the GABA complex.  In addition to being prescribed to instigate sleep, they are also used as tranquilizers and muscle relaxants.

Sleep aids that target the more recently discovered binding sitesThe newer generation of sleeping pills specifically bind to the sleep inducing site,** GABA(A) alpha subunit,** and are more specific in their action.  The most well-known of these drugs are Zolpidem (Ambien), Zalepion (Sonata), and Eszopiclone (Lunesta).

Patients who use these drugs complain of certain side effects.The biggest complaint seems to be that upon awakening the following morning, patients can experience retrograde amnesia, and have no memory of behaviors the night before.This prevalent complaint inspired research and development of alternative choices.

What are melatonin agonists?Melatonin is the hormone that consolidates sleep. It would therefore seem intuitive, that taking melatonin supplements would result in sleep the “natural way.”  In a previous sharepost I discussed that melatonin has benefit when the body’s levels are high, just before bed time.  Adding additional melatonin, in the form of a supplement, offers no further help in the induction of sleep. The best way to use of it, is to shift the sleep-wake clock, by taking it two hours before the ideal time of sleep at which time there is an early rise in the levels of melatonin.  The dose timed then will boost the level artificially.

One sleep aide developed years ago, that targeted the melatonin receptors in the brain as an alternative to existing medications, was Ramelteon (Rozerem).  Excitement over the drug waned since results with use were disappointing, and the drug was priced at $7.00 a pill.

What is the “non 24”?Recently, a new melatonin receptor agonist was developed called Tasimelteon (Heltioz). Heltioz is unique because it lasts longer.  This drug was specifically studied in blind people who do not have the benefit of light as a stimulus of change in the day/night schedule.  The resulting phenomenon is called non-24 rhythm.  You’ve likely seen commercials exploring this phenomenon and advertising the drug.  It’s been a discussion of late in the medical sleep community.

Since the drug has only been studied in blind individuals and not in the general population, the company cannot recommend its general use. Theoretically, it could work on those individuals who have ongoing irregular schedules, as long as it’s taken at the same time every day, one to two hours before going to sleep.

What is the value of short-acting sleep aids?

What can you do when you have no problem falling asleep, but you chronically wake up in the middle of the night?  Or you take a drug to fall asleep, but still awaken in the middle of the night?  It’s not wise to take a sleeping pill (or another sleeping pill) that will last four to six hours and interfere with the waking process.

New agents have been developed that have a very fast and short acting impact on sleep.  Zolpidem (Ambien) is now available in a short-acting form for just that purpose. It’s called Intermezzo, and it can be safely taken in the middle of the night, allowing the individual to wake up refreshed.  This short-acting version also comes as a mist (Zolpimist).

These new agents have promise. What remains, is to find the proper person and In what situation to take it.

Another new drug enters the scene: Suvorexant

Suvorexant (Belsomra) is a new agent from Merck, approved for the treatment of insomnia. It works by inhibiting the receptor for the hormone orexin - the hormone that keeps us awake.  The FDA approved studies to assess the safety of this drug, with dosages of 15 milligrams, though testing with higher doses have been performed in Japan.  According to Medscape:

  • Recommended starting dose: 10 mg PO taken no more than once per night and within 30 minutes of going to bed, with at least 7 hours remaining before the planned time of awakening.

  • Use the lowest dose effective for the patient If 10 mg dose is well-tolerated but not effective, the dose can be increased

The FDA has still issued a warning that there may be next day sleepiness which may affect activities such as driving.”  If you have concerns, or experience lingering effects from the drug, you should speak to your doctor to discuss whether this drug is a good fit for you.

Many wonder if there is a serious downside to suppressing wakefulness

Those of us who treat sleep disorders wonder if there are other unintended consequences of suppressing the hormone, orexin.  To evaluate this question, we look at the condition resulting from orexin deficiency - narcolepsy. In narcolepsy, there is more than just an inability to stay awake.  Sleep is actually disrupted and therefore, not refreshing.  An even greater consideration, orexin plays an important role in regulating the orderly transition between REM and non-Rem stages of sleep.  In narcolepsy, there is presentation of REM during wakeful hours with certain emotional stimuli, such as laughter.  That phenomenon results in sudden muscle paralysis, and the victim can literally slumps to the floor.  This is called cataplexy.

With use of the drug, suvorexant, is there a chance of this phenomenon, cataplexy, happening as well?  With greater use of this drug, time will tell.  For this reason, I am a provider that will wait before comfortably prescribing this new drug.


Sources:

Medscape

FDA.gov

AccessData/FDA

NCBI

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