Types of Prescription Sleep Aids

Prescription sleep aids are categorized based on their mode of action in the body. These drugs act by working on various receptors in the brain to boost relaxation, promote drowsiness, and regulate the sleep-wake cycle.

Sleep medications act quickly, and the duration of effect ranges from short to long, which allows people to work with their doctor to choose the medication that is best for their lifestyle. 

Melatonin Receptor Agonists

Melatonin receptor agonists act on the same receptors as melatonin, a hormone naturally produced in the body that helps regulate the brain’s sleep-wake cycle. This medication mimics the action of melatonin by sending signals throughout the body indicating that it is time to sleep. 

• Melatonin receptor agonists promote sleep by increasing feelings of drowsiness and reducing the amount of time it takes to fall asleep.¹Zisapel N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. British Journal of Pharmacology. 2018;175(16):3190-3199. doi:10.1111/bph.14116
• While this drug helps people fall asleep, it has little to no effect on the duration of sleep, which means it does not help a person stay asleep.²Rozerem. Package Insert. Takeda Pharmaceuticals America, Inc.; 2023

The drug ramelteon (Rozerem) is classified as a melatonin receptor agonist.

Important characteristics of melatonin receptor agonists

Characteristics of ramelteon that impact how it is used include²Rozerem. Package Insert. Takeda Pharmaceuticals America, Inc.; 2023:

• Onset of action. Ramelteon acts very quickly and is generally taken close to bedtime (30 minutes or sooner before bed). Taking this medication with food could delay the onset of action by up to 45 minutes, and it is recommended to avoid taking it with a meal.
• Duration of use. Research shows that ramelteon may be effective for up to 6 months of use. There is no recommended limit to how long this medication should be used. 
• Reproductive hormone changes. Ramelteon has a warning for potential changes in the levels of testosterone and prolactin (reproductive hormones in men and women). These changes may impact menstruation, libido, or fertility. 

It is advisable to discuss concerns or symptoms related to this medication with a doctor.

Benzodiazepines

Benzodiazepines act on receptors in the brain to enhance the sedative effects of gamma-aminobutyric acid (GABA) – a naturally occurring chemical in the body.³Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013;13(2):214-223.

• Activation of the GABA receptors promotes sedative, calming, anticonvulsant, and other similar effects throughout the body.
• Benzodiazepines help people fall asleep and stay asleep. 

Benzodiazepines used as sleep aids include temazepam (Restoril) and triazolam (Halcion).

Important characteristics of benzodiazepines

Characteristics of medications in this class that impact how it is used include⁴Restoril. Package Insert. SpecGx LLC; 2023^,5Halcion. Package Insert. Pharmacia & Upjohn Company LLC; 2023:

• Addiction potential. Tolerance to benzodiazepines develops quickly, and over time, some people may need higher doses to achieve the same effect. Physical dependence on these medications, when used as prescribed, is a potential risk, but addiction usually occurs with abuse or intentional misuse of the drug. 
• Duration of use. Due to the risk of tolerance and addiction, benzodiazepines are recommended for a relatively short period of time (7 to 10 days). These medications are typically prescribed at the lowest effective dose and for the shortest duration.

Due to their safety risks, these medications are less commonly prescribed as sleep aids. 

Benzodiazepine Receptor Agonists (Z-Drugs)

Benzodiazepine receptor agonists, commonly known as Z-drugs, act on GABA receptors with more specificity than benzodiazepines to enhance the sedative effects of GABA. However, they lack the calming and anticonvulsant effects of benzodiazepines.⁶Bouchette D, Quick J. Zolpidem. Nih.gov. Published 2019. https://www.ncbi.nlm.nih.gov/books/NBK442008/

Medications in this class help people fall asleep and stay asleep, and they may also help improve the quality of sleep. Z-drugs receptor agonists include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta).

Important characteristics of benzodiazepine receptor agonists (Z-drugs)

Characteristics of medications in this class that impact how it is used include⁷Ambien. Package Insert. Sanofi-Aventis U.S. LLC; 2019^,8Zaleplon. Package Insert. Aurobindo Pharma Limited; 2021^,9Lunesta. Package Insert. Sunovion Pharmaceuticals Inc.; 2023:

• Onset of action. Z-drugs work quickly and are generally taken close to bedtime (at least 1 hour or less before going to bed). Taking these medications with food could delay the onset of action, and it is best to avoid taking a dose with or immediately after a meal.
• Starting dose. Physiologically, this drug is processed differently in men and women. For this reason, medications in this class are started at a lower dose for women and some older adults. Starting at a higher dose in these populations may increase the risk of potential side effects and adverse events.
• Duration of use. These medications are generally recommended for short-term use (4-5 weeks), with the exception of eszopiclone (Lunesta), which may be safely and effectively used for up to 6 months. More research is needed to establish the safety of these sleep aids for longer periods of time. 
• Duration of impairing effects. These medications can cause impairment of physical and mental functions (including impaired driving) if a person does not get a full night’s sleep. Z-drugs are typically indicated in individuals who intend to get at least 7 to 8 hours of sleep.

Z-drugs also have a low potential to cause physical dependence but may cause rebound insomnia (temporary worsening of sleep problems) when the medication is stopped. 

Dual Orexin Receptor Antagonists (DORAs)

DORAs act by blocking specific signals in the brain that allow people to remain awake for extended periods of time during the day. These wakefulness signals are often overactive in people with insomnia.¹⁰Kishi T, Nishida M, Koebis M, et al. Evidence-based insomnia treatment strategy using novel orexin antagonists: A review. Neuropsychopharmacol Rep. 2021;41(4):450-458. doi:10.1002/npr2.12205

These medications help people fall asleep and stay asleep.

Sleep aids classified as DORAs antagonists include suvorexant (Belsomra), daridorexant (Quviviq), and lemborexant (Dayvigo). 

Important characteristics of dual orexin receptor antagonists

Characteristics of medications in this class that impact how it is used include¹¹Belsomra. Package Insert. Merck Sharp & Dohme LLC; 2023^,12Quviviq. Package Insert. Idorsia Pharmaceuticals Ltd; 2023^,13Dayvigo. Package Insert. Eisai Inc.; 2023:

• Onset of action. DORAs act fast and are generally taken just before bedtime (no more than 30 minutes before going to bed). Taking these medications with food could delay the onset of action, and it is best to avoid taking a dose with or immediately after a meal.
• Sleep-wake transition events. DORAs can potentially cause abnormal experiences, such as hallucinations, during the transition between sleeping and waking up. These events do not occur for everyone, but the risk may be increased in people who have a history of similar experiences.
• Duration of use. Research shows that these medications are safe and effective to use for longer periods of time (up to 12 months) compared to other sleep aids.¹⁴Kunz D, Dauvilliers Y, Benes H, et al. Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder. CNS Drugs. 2023;37(1):93-106. doi:10.1007/s40263-022-00980-8^,15Yardley J, Kärppä M, Inoue Y, et al. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep Med. 2021;80:333-342. doi:10.1016/j.sleep.2021.01.048 DORAs are generally considered the preferred type of sleep aid for people with chronic insomnia.
• Contraindication. These drugs are not prescribed in people with narcolepsy due to a higher risk of serious adverse events.

DORAs have little to no risk of dependence, addiction, tolerance, or withdrawal, and side effects are well tolerated.¹⁶Muehlan C, Vaillant C, Zenklusen I, Kraehenbuehl S, Dingemanse J. Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders. Expert Opin Drug Metab Toxicol. 2020;16(11):1063-1078. doi:10.1080/17425255.2020.1817380

Antidepressants as Sleep Aids

Antidepressant drugs with sedating side effects may help manage insomnia in some people. Doxepin (Silenor) is the only FDA-approved antidepressant for the treatment of insomnia. Other antidepressants may be used off-label (not officially approved by the FDA) as sleep aids. 

Doxepin (Silenor) produces sedating effects at low doses and helps people stay asleep. This medication may be used in people with or without depression.

Doxepin: FDA-approved antidepressant for insomnia

Characteristics of doxepin that impacts how it is used include¹⁷Silenor. Package Insert. Currax Pharmaceuticals LLC; 2023:

• Onset of action. Doxepin produces sedation quickly and is generally taken immediately before bedtime (no more than 30 minutes before going to bed).
• Interaction with food. Food can slow the absorption of this medication and decrease the sedating effects. It is recommended to wait at least 3 hours in between eating and taking doxepin.
• Duration of use. Research shows that doxepin may be effective in improving sleep for up to 3 months. More research is needed on the long-term use and safety of this medication.

Doxepin is generally not associated with dependence or withdrawal symptoms. Additional factors may affect the use of dual orexin receptor antagonists; it is important to discuss these and other concerns with a doctor.

Off-label antidepressants for insomnia

A few other antidepressants with sedating side effects may improve sleep for people with depression, but there is not much evidence to show how effective these medications are. Doctors individualize the doses of these medications based on improvement of sleep and tolerability of side effects.

The antidepressants commonly used off-label as sleep aids are:

• Trazodone
• Mirtazapine (Remeron)
• Amitriptyline 

Antidepressants as sleep aids should generally be avoided in people without a diagnosis of depression because the duration of sedative effects in these medications is shorter than other sleep aids, and the potential side effects may cause more risk than benefit.¹⁸Everitt H, Baldwin DS, Stuart B, et al. Antidepressants for insomnia in adults. Cochrane Database Syst Rev. 2018;5(5):CD010753. Published 2018 May 14. doi:10.1002/14651858.CD010753.pub2

Additional factors may affect the use of the drugs mentioned on this page, and it is important to discuss these and other concerns with a doctor.