Occasional, short-term insomnia affects 30-50% of the population while chronic insomnia affects up to at least five to 10% of Americans. If you have trouble sleeping or struggle with insomnia, you may have wondered what the best prescription sleep aid would be for you. 

Prescription sleep medications need to be prescribed by a doctor to treat specific sleep disorders. 

The word “best”, can be a loaded term in the context of sleep medication. Because there are a lot of cons to weigh when deciding whether or not to use prescription sleeping pills. 

As strong advocates for holistic approaches to improving sleep health, Remrise provides this list of prescription sleep medications for informational purposes only. The purpose of this article is purely informational and is intended only to shed light on the different sleep medications that exist, what they do, and their possible side effects.

Remrise does not provide recommendations about sleep medications, nor does it sell sleep medications — prescription or over the counter. 

Pros and cons of sleeping medicine for insomnia

Sleep medications are only effective in treating short-term, or acute, insomnia for periods of less than two weeks. Insomnia can be acute or chronic depending on the symptoms and the individual. In cases of chronic insomnia, which is defined as insomnia lasting over one month, there are no pharmaceutical solutions that have been clinically tested for extended periods. 

In these cases, holistic solutions such as Cognitive Behavioral Therapy for Insomnia (CBT-I) have been shown to be most effective alongside lifestyle changes and sleep hygiene implementations. 

There are multiple types of insomnia. Different medications are indicated for different types of insomnia. [1, 2, 3] 

There are advantages and disadvantages to taking sleep medications. One reason why sleeping meds have become a popular solution for addressing sleep issues is that most people will see a quick improvement in their sleep initially, which is to say they might fall asleep more quickly than they might otherwise. The most commonly used sleep medications are for short-term or occasional insomnia.  

These medications are usually well-tolerated for short periods. However, you can quickly become tolerant of some sleeping meds and, in some cases, dependent on them to sleep. Many of these medications come with a serious risk of adverse effects. 

It’s worth noting that there are no prescribed sleep medications that have been clinically tested for periods lasting beyond just a few days. Additionally, in April 2019 the Food and Drug Administration began requiring insomnia drugs including Ambien, Sonata, and Lunesta to print a black warning on these sleep drugs, the FDA’s strongest level of notification regarding the associated risks.

The different classes of sleep medications

Benzodiazepines

Benzodiazepines are commonly prescribed for acute insomnia, anxiety disorders, panic attacks, seizures, and more. These short-acting drugs work by enhancing the action of the neurotransmitter GABA in the brain. This neurotransmitter is inhibitory, meaning it reduces activity in the nervous system, thereby promoting feelings of relaxation and drowsiness. 

There are a wide variety of benzodiazepines with varying half-lives, but some of the most common include clonazepam (Klonopin), lorazepam (Ativan), diazepam (Valium), alprazolam (Xanax), temazepam (Restoril), triazolam (Halcion), estazolam, and flurazepam.

Pros:

  • Benzodiazepines have been shown to be effective in reducing the time to fall asleep and increasing total sleep duration.[1] 
  • May alleviate motor symptoms that can disturb sleep, such as periodic limb movements and physically acting out dreams in REM sleep behavior disorder.
  • The anxiolytic effects may alleviate psychological distress, such as anxiety and panic, that can disturb sleep.

Cons:

  • Long-term use carries a significant chance of dependency because of the development of tolerance to the effects of the drug over time.
  • Discontinuation after chronic use is associated with severe withdrawal symptoms, including rebound insomnia.
  • Reduces the duration of deep, slow-wave sleep.
  • Adverse side effects such as memory impairment, daytime drowsiness, dizziness, and light-headedness
  • Potential for increased risk of dementia with benzodiazepines in elderly.

Z-drugs

The Z-drug sedative-hypnotics emerged in the late 1980s and early 1990s. They are a commonly-prescribed line of nonbenzodiazepine drugs for short-term insomnia. Z-drugs include zolpidem, zopiclone, eszopiclone, and zaleplon. 

Z-drugs are benzodiazepine receptor agonists, which means they act similarly to benzodiazepines by enhancing the activity of GABA at the same GABA receptors in the brain. When these receptors are activated, the brain stops becoming excited which helps you feel tired.[5]  

Pros:

  • Z-drugs may help increase total sleep duration and decrease the time it takes to fall asleep.
  • Fewer withdrawal symptoms and not as dependency-forming compared to benzodiazepines.
  • Shorter half-life and limited duration of action lessen the intensity of next-day side effects.

Cons:

  • Some individuals may find these drugs are not powerful enough to improve sleep.
  • Adverse side effects such as next-day drowsiness, dizziness, vivid dreams, and parasomnias such as sleepwalking.
  • Efficacy and safety of long-term use are largely unknown. 

Orexin receptor antagonists

The orexin receptor antagonists are the most recently approved line of drugs to treat insomnia by the FDA. Instead of enhancing the action of GABA, these drugs work by inhibiting the activity of a chemical called orexin in the brain. 

Since orexin plays an important role in regulating arousal and wakefulness, inhibiting the action of this chemical can help improve the symptoms of insomnia. Suvorexant (Belsomra) is the first orexin receptor antagonist approved for insomnia treatment.

Pros:

  • These drugs may be effective for sleep-maintenance insomnia and reducing the time it takes to fall asleep. 
  • Orexin antagonists have high specificity for orexin receptors, so these drugs have fewer undesirable side effects compared to the GABA-boosting drugs. 
  • Have not been shown to change sleep architecture like benzodiazepines.

Cons:

  • Possible adverse side effects include vivid dreams, nightmares, sleep paralysis, muscle weakness, and next-day sleepiness.[2,15,16] 
  • Psychological dependence similar to zolpidem is possible in some individuals.

Antidepressants

Antidepressants are commonly prescribed off-label for insomnia, or for primary treatment of depression which can frequently cause secondary insomnia. The older tricyclic antidepressants carry sedative effects and are commonly prescribed for insomnia treatment. These include doxepin (Sinequan) and amitriptyline (Elavil, Endep). 

Other antidepressants such as trazodone (Desyrel), nefazodone (Serzone), and mirtazapine (Remeron) are frequently prescribed as well. These antidepressants work by blocking the action of histamine, a chemical that promotes wakefulness, and/or by increasing the levels of serotonin in the brain by blocking its reuptake. 

Pros:

  • May reduce the time it takes to fall asleep and nighttime arousals.
  • May improve symptoms of anxiety and depression which are commonly associated with insomnia symptoms.
  • More appropriate for long-term use compared to benzodiazepines and Z-drugs.

Cons:

  • Sedative antidepressants tend to suppress REM sleep and lengthen the time it takes to enter REM.
  • Possible adverse side effects such as dizziness, dry mouth, upset stomach, sexual dysfunction, abnormal leg movements, and weight gain
  • Tricyclics with anticholinergic effects such as doxepin and amitryptiline have been associated with an increased risk of dementia

Melatonin receptor agonists

Melatonin is a hormone produced naturally in the pineal gland of the brain that plays a crucial role in regulating our sleep-wake cycles. The production of melatonin peaks in the late evening, which helps to initiate sleep. 

To boost the levels of this sleepiness-inducing hormone, individuals may supplement with synthetic versions of melatonin, which can be purchased over the counter, or they may use prescribed melatonin receptor agonists such as Ramelteon (Rozerem). Melatonin production and melatonin receptor potency tend to decrease with age, so these drugs may be more effective in the elderly. 

Pros:

  • May improve sleep onset by about nine minutes in some individuals.
  • No significant abuse potential nor severe withdrawal symptoms.
  • Comparatively few side effects compared to the other drug classes. 

Cons:

  • Synthetic melatonin has been shown to have very limited efficacy but may help some fall asleep a bit more quickly.
  • Possible side effects of Ramelteon include somnolence, dizziness, nausea, headache, and fatigue.

Sleep medication treatment use cases 

Sleep-Onset Insomnia

(Regular difficulty falling asleep)

Sleep-Maintenance Insomnia

(Regular difficulty staying asleep)

Both Sleep-Onset AND Sleep-Maintenance Insomnia

Eszopiclone

Zaleplon

Zolpidem

Temazepam

Triazolam

Ramelteon

Eszopiclone

Zolpidem

Temazepam

Doxepin

Amitriptyline

Suvorexant

Eszopiclone

Zolpidem

Temazepam


Sleep medications to watch out for

According to the Journal of Clinical Sleep Medicine, some of the medications you commonly hear about for improving sleep are often not recommended.[2] 

This can be due to side effects, lack of efficacy, or a lack of data supporting their use in the treatment of insomnia. The following medications are not recommended for insomnia by the Journal of Clinical Sleep Medicine:

  • Antihistamines such as doxylamine (Unisom) and diphenhydramine (Benadryl)
  • Tiagabine 
  • Trazodone

What is a Sleep Specialist? 

A sleep specialist is a specially trained doctor who treats issues related to sleep and sleep health. These doctors are board-certified to help diagnose and potentially treat sleeping disorders. Sleep specialists commonly work in sleep centers or sleep clinics. 

People often see sleep specialists when they feel their sleep is not sufficient. Sleep specialists may be either a physician or even a psychologist. 

How Can a Sleep Specialist Help You? 

Sleep specialists can include physicians and other medical professionals who deal with sleep disorders such as insomnia, sleep apnea, narcolepsy, restless leg syndrome, and more. 

Sleep specialists listen to your experience with sleep disturbance and usually do a sleep test called a polysomnogram. A polysomnogram is a diagnostic test that measures different body functions like muscle tension and airflow while you sleep. This can help determine why your sleep is being disturbed. [21] For more on sleep specialists, read this article.

If the sleep specialist has an MD or DO degree, they are able to prescribe medications. On the other hand, if they have a psychology background (such as a Ph.D.) they cannot prescribe medications themselves, and so they may refer patients to another specialist that can prescribe appropriate medication.

Conclusion

There are many sleep medications available. There is no single best sleep medication. The best prescription sleep aid for you depends on many factors related to your sleep condition. 

Sleep specialists are the best way to determine the cause of disturbed sleep. Specialists can also help decide the best way to treat insomnia and other sleep disorders. 

Aside from physical sleep disorders like sleep apnea, the good news is that for most, insomnia is a temporary sleep disorder, which in its acute form shouldn’t last for more than a month. That being the case, there are numerous behavior changes you can make sure you have an expedient recovery from your sleep problems. 

Glossary

Half-life: The time it takes for your body to eliminate half of the drug
REM sleep behavior disorder: A disorder characterized by disruptions in muscle paralysis during REM sleep, leading individuals to physically act out their dreams. 
Parasomnia: Sleep disorders that involve abnormal physical or verbal behaviors that disrupt sleep. May occur in arousal from REM sleep or NREM sleep.
Secondary insomnia: Insomnia caused as a side effect of another disorder. Common disorders that produce insomnia include anxiety, depression, posttraumatic stress disorder, 
Agonists: A chemical that binds to a receptor and activates the receptor, leading to a biological response. In this way, agonists act like the substance that typically binds to these receptors.
Antagonists: Chemicals that reduce the activity of another drug (typically the agonist). Antagonists typically block the receptor that the agonist binds to, rendering them ineffective. 

References 

  1.  Holbrook A, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000;162: 225-33
  2. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-349.
    1. DOI: 10.5664/jcsm.6470
  3. Chawla J, Park Ya, Passaro EA, et al. Insomnia. Medscape website. http://emedicine.medscape.com/article/1187829-overview#aw2aab6b2b2
  4. Ellis JG, Perlis ML, Neale LF, Espie CA, Bastien CH. The natural history of insomnia: focus on prevalence and incidence of acute insomnia. J Psychiatr Res. 2012 Oct;46(10):1278-85.
    1. DOI: 10.1016/j.jpsychires.2012.07.001
  5. Moen MD, Plosker GL. Zolpidem extended-release. CNS Drugs. 2006;20(5):419-26; discussion 427-8.
    1. DOI: 10.2165/00023210-200620050-00006
  6. Zolpidem. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  7. Ambien (zolpidem) [package insert]. Bridgewater, NJ; sanofi-aventis U.S. LLC ; Revised 10/01/2014.
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019908s037lbl.pdf
  8. Eszopiclone. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  9. Lunesta (eszopiclone) [package insert]. Marlborough, MA; Sunovion Pharmaceuticals Inc.; Revised 5/01/2014.
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021476s030lbl.pdf
  10. Zaleplon. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  11. Sonata (zaleplon) [package insert]. Bristol, TN; King Pharmaceuticals, Inc.; Revised 12/01/2007
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020859s011lbl.pdf
  12. Temazepam. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  13. Restoril (temazepam) [package insert]. Hazelwood, MO. Mallinckrodt Inc.; Revised 09/2016.
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018163s064lbl.pdf
  14. Triazolam. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  15. Halcion (triazolam) [package insert]. New York, NY. Pharmacia & Upjohn Co.; Revised 09/2016.
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017892s049lbl.pdf
  16. Suvorexant. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  17. Belsomra (suvorexant) [package insert]. Whitehouse Station, NJ. Merck & Co., Inc.; Issued 2014.
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204569s000lbledt.pdf
  18. Ramelteon. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  19. Rozerem (ramelteon) [package insert]. Deerfield, IL. Takeda Pharmaceuticals America, Inc.; Revised 11/2010.
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021782s011lbl.pdf
  20. Doxepin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com.  Accessed July 11, 2019.
  21. Silenor (doxepin) [package insert]. San Diego, CA. Somaxon Pharmaceuticals, Inc.; Issued 3/2010
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022036lbl.pdf
  22. Sleep Doctor: Sleep Disorder Specialist. American Sleep Association (ASA) Website. https://www.sleepassociation.org/health-professionals/sleep-doctor/