Benzodiazepines are sedating because they enhance the action of GABA, a neurotransmitter that slows activity in the brain. Examples of benzodiazepines are flurazepam, triazolam, temazepam, diazepam, alprazolam, and lorazepam.
Non-benzodiazepine hypnotics also affect the chemical GABA, but are more targeted and affect only specific parts of the GABA receptor. Examples of non-benzodiazepine sleep aids are zolpidem, eszopiclone, and zaleplon.
Antidepressants are sometimes prescribed for sleep difficulties because, through altering chemicals such as serotonin and norepinephrine, they can have a sedating effect. Trazodone and amitriptyline are antidepressants that are sometimes prescribed as sleep aids.
Diphenhydramine is an over-the-counter sleep aid. It’s an antihistamine that is commonly used to relieve cold symptoms, but it also has a sedating effect.
Orexin receptor antagonistsblock the activity of the chemical orexin in the brain, which may inhibit arousal and promote sleep. Belsomra (suvorexant) is the only FDA-approved orexin receptor antagonist currently available on the market.
In the last several years, research papers have reported on the effectiveness of orexin antagonists (drugs that block the action of orexin), and results so far suggest that they may be effective in promoting sleep.
In clinical studies, when compared to placebos, orexin sleep aids have generally been shown to shorten the amount of time it takes people to fall asleep, increase the amount of total time they spend asleep, and to improve people’s subjective reports of sleepiness.
Orexins sleep aids are new, so there is not as much data on their effectiveness and side effects. However, early studies of orexins antagonists have found them to be well tolerated and to have few side effects.
Many current over-the-counter and prescription sleep aids have wide-reaching sedative effects and sometimes cause confusion, next-day drowsiness, worsening of sleep apnea symptoms, and an increase in the risk of falls. Orexins work on a targeted chemical system—one that is mainly involved in arousal. The hope is that they will cause fewer side effects than other sleep aids on the market.
Some researchers are encouraged by the information known so far about this new class of sleep aid. However, additional clinical studies are needed to understand more about orexins, as they may have side effects of their own. Researchers are continuing to study these medications to find out if they cause next day drowsiness or mood changes, as well as how they change “sleep architecture” (the structure and pattern of sleep); for example, orexins may change the amount of REM sleep a person gets.