Editing Insomnia (section)

=== Medications ===
{{See also|Hypnotic}}
<!--"Sleep aid", "Sleep aids", and "Sleep Aids" redirect to this section. If the section name (Medications) is changed, please change the redirects as well.-->

Many people with insomnia use [[sleeping tablet]]s and other [[sedative]]s. In some places, medications are prescribed in over 95% of cases.<ref>{{cite journal | vauthors = Charles J, Harrison C, Britt H | title = Insomnia | journal = Australian Family Physician | volume = 38 | issue = 5 | pages = 283 | date = May 2009 | pmid = 19458795 | url = http://www.racgp.org.au/afp/200905/200905beach.pdf | archive-url = https://web.archive.org/web/20110312061834/http://www.racgp.org.au/afp/200905/200905beach.pdf | archive-date = 12 March 2011 }}</ref> They, however, are a second line treatment.<ref>{{cite journal | vauthors = Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD | title = Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians | journal = Annals of Internal Medicine | volume = 165 | issue = 2 | pages = 125–133 | date = July 2016 | pmid = 27136449 | doi = 10.7326/m15-2175 | doi-access = free }}</ref> In 2019, the US [[Food and Drug Administration]] stated it is going to require warnings for [[eszopiclone]], [[zaleplon]], and [[zolpidem]], due to concerns about serious injuries resulting from abnormal sleep behaviors, including [[sleepwalking]] or driving a vehicle while asleep.<ref>{{cite web |title=FDA adds Boxed Warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia |publisher=US Food and Drug Administration |access-date=2 May 2019 |date=30 April 2019 |archive-date=2 May 2019 |archive-url=https://web.archive.org/web/20190502051204/https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia |url-status=live }}</ref>

The percentage of adults using a prescription sleep aid increases with age. During 2005–2010, about 4% of U.S. adults aged 20 and over reported that they took prescription sleep aids in the past 30 days. Rates of use were lowest among the youngest age group (those aged 20–39) at about 2%, increased to 6% among those aged 50–59, and reached 7% among those aged 80 and over. More adult women (5%) reported using prescription sleep aids than adult men (3%). Non-Hispanic white adults reported higher use of sleep aids (5%) than non-Hispanic black (3%) and Mexican-American (2%) adults. No difference was shown between non-Hispanic black adults and Mexican-American adults in use of prescription sleep aids.<ref name="pmid24152538">{{cite journal | vauthors = Chong Y, Fryer CD, Gu Q | title = Prescription sleep aid use among adults: United States, 2005-2010 | journal = NCHS Data Brief | volume = | issue = 127 | pages = 1–8 | date = August 2013 | pmid = 24152538 | doi = | url = https://purl.fdlp.gov/GPO/gpo41892 | archive-url = https://web.archive.org/web/20210828125123/https://permanent.fdlp.gov/gpo41892/db127.pdf | archive-date=2021-08-28 | location = Hyattsville, Md. | publisher = [[United States Department of Health and Human Services|U.S. Department of Health and Human Services]], [[Centers for Disease Control and Prevention]], [[National Center for Health Statistics]]}}</ref>

==== Antihistamines ====
As an alternative to taking prescription drugs, some evidence shows that an average person seeking short-term help may find relief by taking [[over-the-counter]] [[antihistamines]] such as [[diphenhydramine]] or [[doxylamine]].<ref name="BBDinsomnia-2">{{Cite journal |author1=Consumer Reports |author1-link=Consumer Reports |author2=Drug Effectiveness Review Project |author2-link=Drug Effectiveness Review Project |date=January 2012 |title=Evaluating Newer Sleeping Pills Used to Treat: Insomnia. Comparing Effectiveness, Safety, and Price |journal=Best Buy Drugs |pages=3, 8, 11 |url=http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/InsomniaUpdate-FINAL-July2008.pdf |access-date=4 June 2013 |url-status=live |archive-url=https://web.archive.org/web/20131209122641/http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/InsomniaUpdate-FINAL-July2008.pdf |archive-date=9 December 2013 }}</ref> Diphenhydramine and doxylamine are widely used in nonprescription sleep aids. They are the most effective over-the-counter sedatives currently available, at least in much of Europe, Canada, Australia, and the United States, and are more sedating than some prescription [[hypnotic]]s.<ref name="drugbankDB00366">{{cite web | url = http://www.drugbank.ca/cgi-bin/getCard.cgi?CARD=DB00366.txt | work = DrugBank | id = DB00366 | title = Doxylamine | archive-url = https://web.archive.org/web/20091203012047/http://www.drugbank.ca/cgi-bin/getCard.cgi?CARD=DB00366.txt | archive-date=3 December 2009 }}</ref> Antihistamine effectiveness for sleep may decrease over time, and [[anticholinergic]] side-effects (such as dry mouth) may also be a drawback with these particular drugs. While addiction does not seem to be an issue with this class of drugs, they can induce dependence and rebound effects upon abrupt cessation of use.<ref>{{cite journal | vauthors = Lie JD, Tu KN, Shen DD, Wong BM | title = Pharmacological Treatment of Insomnia | journal = P & T | volume = 40 | issue = 11 | pages = 759–771 | date = November 2015 | pmid = 26609210 | pmc = 4634348 | doi =  }}</ref> However, people whose insomnia is caused by restless legs syndrome may have worsened symptoms with antihistamines.<ref>{{cite web|title=Restless Legs Syndrome Fact Sheet {{!}} National Institute of Neurological Disorders and Stroke|url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Restless-Legs-Syndrome-Fact-Sheet|website=www.ninds.nih.gov|access-date=29 August 2017|url-status=live|archive-url=https://web.archive.org/web/20170728021833/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Restless-Legs-Syndrome-Fact-Sheet|archive-date=28 July 2017}}</ref>

==== Antidepressants ====
While insomnia is a common symptom of depression, [[antidepressant]]s are effective for treating sleep problems whether or not they are associated with depression. While all antidepressants help regulate sleep, some antidepressants, such as [[amitriptyline]], [[doxepin]], [[mirtazapine]], [[trazodone]], and [[trimipramine]], can have an immediate sedative effect and are prescribed to treat insomnia.<ref>{{cite journal | vauthors = Bertschy G, Ragama-Pardos E, Muscionico M, Aït-Ameur A, Roth L, Osiek C, Ferrero F | title = Trazodone addition for insomnia in venlafaxine-treated, depressed inpatients: a semi-naturalistic study | journal = Pharmacological Research | volume = 51 | issue = 1 | pages = 79–84 | date = January 2005 | pmid = 15519538 | doi = 10.1016/j.phrs.2004.06.007 }}</ref> Trazodone was at the beginning of the 2020s the biggest prescribed drug for sleep in the United States despite not being indicated for sleep.<ref name="Dunleavy">{{Cite web | vauthors = Dunleavy K |date=2023-04-07 |title=Idorsia petitions DEA to de-schedule its insomnia drug—plus Merck and Eisai rivals |url=https://www.fiercepharma.com/pharma/idorsia-petitions-dea-get-its-insomnia-drug-quviviq-and-others-dora-class-controlled |access-date=2023-08-31 |website=Fierce Pharma |archive-date=2023-08-31 |archive-url=https://web.archive.org/web/20230831190635/https://www.fiercepharma.com/pharma/idorsia-petitions-dea-get-its-insomnia-drug-quviviq-and-others-dora-class-controlled |url-status=live }}</ref>

Amitriptyline, doxepin, and trimipramine all have [[antihistaminergic]], [[anticholinergic]], [[antiadrenergic]], and [[antiserotonergic]] properties, which contribute to both their therapeutic effects and side effect profiles, while mirtazapine's actions are primarily antihistaminergic and antiserotonergic and trazodone's effects are primarily antiadrenergic and antiserotonergic. Mirtazapine is known to decrease sleep latency (i.e., the time it takes to fall asleep), promoting sleep efficiency and increasing the total amount of sleeping time in people with both depression and insomnia.<ref>{{cite journal | vauthors = Winokur A, DeMartinis NA, McNally DP, Gary EM, Cormier JL, Gary KA | title = Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia | journal = The Journal of Clinical Psychiatry | volume = 64 | issue = 10 | pages = 1224–29 | date = October 2003 | pmid = 14658972 | doi = 10.4088/JCP.v64n1013 }}</ref><ref>{{cite journal | vauthors = Schittecatte M, Dumont F, Machowski R, Cornil C, Lavergne F, Wilmotte J | s2cid = 25351993 | title = Effects of mirtazapine on sleep polygraphic variables in major depression | journal = Neuropsychobiology | volume = 46 | issue = 4 | pages = 197–201 | year = 2002 | pmid = 12566938 | doi = 10.1159/000067812 }}</ref>

[[Agomelatine]], a melatonergic antidepressant with claimed sleep-improving qualities that does not cause daytime drowsiness,<ref>{{cite journal | vauthors = Le Strat Y, Gorwood P | s2cid = 29745284 | title = Agomelatine, an innovative pharmacological response to unmet needs | journal = Journal of Psychopharmacology | volume = 22 | issue = 7 Suppl | pages = 4–8 | date = September 2008 | pmid = 18753276 | doi = 10.1177/0269881108092593 }}</ref> is approved for the treatment of depression though not sleep conditions in the European Union<ref name="emea">{{cite web |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000915/WC500046227.pdf |title=Summary of Product Characteristics |publisher=European Medicine Agency |access-date=14 October 2013 |url-status=live |archive-url=https://web.archive.org/web/20141029015615/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000915/WC500046227.pdf |archive-date=29 October 2014 }}</ref> and [[Australia]].<ref name="PI">{{cite web |title=VALDOXAN® Product Information |url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07273-3 |work=TGA eBusiness Services |publisher=Servier Laboratories Pty Ltd |access-date=14 October 2013 |format=PDF |date=23 September 2013 |url-status=live |archive-url=https://web.archive.org/web/20170324132859/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07273-3 |archive-date=24 March 2017 }}</ref> After trials in the United States, its development for use there was discontinued in October 2011<ref>{{cite web | url = http://www.scripintelligence.com/home/Novartis-drops-future-blockbuster-agomelatine-322880 | title = Novartis drops future blockbuster agomelatine. | archive-url = https://web.archive.org/web/20111111121308/http://www.scripintelligence.com/home/Novartis-drops-future-blockbuster-agomelatine-322880 | archive-date=11 November 2011 | work = Scrip Intelligence | date = 25 October 2011 | access-date = 30 October 2011 }}</ref> by [[Novartis]], who had bought the rights to market it there from the European pharmaceutical company [[Servier]].<ref name="Bentham">{{cite news |url=http://www.servier.co.uk/news/news-details.asp?StoryID=76 |title=Servier and Novartis sign licensing agreement for agomelatine, a novel treatment for depression | vauthors = Bentham C |date=29 March 2006 |publisher=Servier UK |access-date=15 May 2009 |archive-url=https://web.archive.org/web/20090416210513/http://www.servier.co.uk/news/news-details.asp?StoryID=76 |archive-date=16 April 2009 |url-status=dead }}</ref>

A 2018 [[Cochrane review]] found the safety of taking antidepressants for insomnia to be uncertain with no evidence supporting long term use.<ref>{{cite journal | vauthors = Everitt H, Baldwin DS, Stuart B, Lipinska G, Mayers A, Malizia AL, Manson CC, Wilson S | title = Antidepressants for insomnia in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | pages = CD010753 | date = May 2018 | issue = 5 | pmid = 29761479 | pmc = 6494576 | doi = 10.1002/14651858.CD010753.pub2 }}</ref>

==== Melatonin agonists ====
[[Melatonin receptor agonist]]s such as [[melatonin (medication)|melatonin]] and [[ramelteon]] are used in the treatment of insomnia. The evidence for melatonin in treating insomnia is generally poor.<ref name=Bra2015/> There is low-quality evidence that it may speed the onset of sleep by 6{{nbsp}}minutes.<ref name=Bra2015/> Ramelteon does not appear to speed the onset of sleep or the amount of sleep a person gets.<ref name="Bra2015">{{cite book | vauthors = Brasure M, MacDonald R, Fuchs E, Olson CM, Carlyle M, Diem S, Koffel E, Khawaja IS, Ouellette J, Butler M, Kane RL, Wilt TJ | chapter = Management of Insomnia Disorder | title = AHRQ Comparative Effectiveness Reviews | location = Rockville (MD) | publisher = Agency for Healthcare Research and Quality (US) | date = December 2015 | pmid = 26844312 }}</ref>

The usage of melatonin as a treatment for insomnia in adults has increased from 0.4% between 1999 and 2000 to nearly 2.1% between 2017 and 2018.<ref>{{Cite web |date=2022-02-28 |title=Use of melatonin supplements rising among adults |url=https://www.nih.gov/news-events/nih-research-matters/use-melatonin-supplements-rising-among-adults |access-date=2022-06-29 |website=National Institutes of Health (NIH) |language=EN |archive-date=2022-06-29 |archive-url=https://web.archive.org/web/20220629045236/https://www.nih.gov/news-events/nih-research-matters/use-melatonin-supplements-rising-among-adults |url-status=live }}</ref>

While the use of melatonin in the short-term has been proven to be generally safe and is shown not to be a dependent medication, side effects can still occur.<ref name="Pros and cons of melatonin">{{Cite web |title=Pros and cons of melatonin |url=https://www.mayoclinic.org/healthy-lifestyle/adult-health/expert-answers/melatonin-side-effects/faq-20057874 |access-date=2024-05-01 |website=Mayo Clinic |language=en}}</ref>

Most common side effects of melatonin include:<ref name="Pros and cons of melatonin"/>

* Headache 
* Dizziness
* Nausea
* Daytime drowsiness

[[Prolonged-release melatonin]] may improve the quality of sleep in older people with minimal side effects.<ref>{{cite journal | vauthors = Lyseng-Williamson KA | s2cid = 1403262 | title = Melatonin prolonged release: in the treatment of insomnia in patients aged ≥55 years | journal = Drugs & Aging | volume = 29 | issue = 11 | pages = 911–23 | date = November 2012 | pmid = 23044640 | doi = 10.1007/s40266-012-0018-z }}</ref><ref>{{cite journal | vauthors = Lemoine P, Zisapel N | s2cid = 23291045 | title = Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia | journal = Expert Opinion on Pharmacotherapy | volume = 13 | issue = 6 | pages = 895–905 | date = April 2012 | pmid = 22429105 | doi = 10.1517/14656566.2012.667076 }}</ref>

Studies have also shown that children who have an [[autism spectrum disorder]] or a learning disability, such as [[attention-deficit hyperactivity disorder]] (ADHD) or related [[neurological]] diseases, can benefit from the use of melatonin. This is because they often have trouble sleeping due to their disorders. For example, children with ADHD tend to have trouble falling asleep because of their [[hyperactivity]] and, as a result, tend to be tired during most of the day. Another cause of insomnia in children with ADHD is the use of stimulants to treat their disorder. Children who have ADHD then, as well as the other disorders mentioned, may be given melatonin before bedtime to help them sleep.<ref>{{cite journal | vauthors = Sánchez-Barceló EJ, Mediavilla MD, Reiter RJ | title = Clinical uses of melatonin in pediatrics | journal = International Journal of Pediatrics | volume = 2011 | pages = 892624 | year = 2011 | pmid = 21760817 | pmc = 3133850 | doi = 10.1155/2011/892624 | doi-access = free }}</ref>

==== Benzodiazepines ====
[[File:Normison.jpg|thumb|Normison ([[temazepam]]) is a [[benzodiazepine]] commonly prescribed for insomnia and other [[sleep disorders]].<ref>{{cite web | url = http://www.websters-online-dictionary.org/definitions/Temazepam | title = Temazepam | archive-url = https://web.archive.org/web/20130530212815/http://www.websters-online-dictionary.org/definitions/Temazepam | archive-date=30 May 2013 | work = Websters-online-dictionary.org. | access-date = 20 November 2011 }}</ref>]]

The most commonly used class of hypnotics for insomnia are the [[benzodiazepine]]s.<ref name=Psych4th>{{cite book | vauthors = Geddes J, Price J, McKnight R, Gelder M, Mayou R |title=Psychiatry |date=2012 |publisher=Oxford University Press |location=Oxford |isbn=978-0-19-923396-0 |edition=4th}}</ref>{{rp|363}} Benzodiazepines are [[statistical significance|not significantly]] better for insomnia than [[antidepressant]]s.<ref name="pmid17619935">{{cite journal | vauthors = Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M | title = The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs | journal = Journal of General Internal Medicine | volume = 22 | issue = 9 | pages = 1335–50 | date = September 2007 | pmid = 17619935 | pmc = 2219774 | doi = 10.1007/s11606-007-0251-z }}</ref> Chronic users of [[hypnotic]] medications for insomnia do not have better sleep than chronic insomniacs not taking medications. In fact, chronic users of hypnotic medications have more regular night-time awakenings than insomniacs not taking hypnotic medications.<ref>{{cite journal | vauthors = Ohayon MM, Caulet M | s2cid = 20655328 | title = Insomnia and psychotropic drug consumption | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 19 | issue = 3 | pages = 421–31 | date = May 1995 | pmid = 7624493 | doi = 10.1016/0278-5846(94)00023-B }}</ref> Many have concluded that these drugs cause an unjustifiable risk to the individual and to [[public health]] and lack evidence of long-term effectiveness. It is preferred that hypnotics be prescribed for only a few days at the lowest effective dose and avoided altogether wherever possible, especially in the elderly.<ref>{{cite journal | s2cid = 40188442 | title = What's wrong with prescribing hypnotics? | journal = Drug and Therapeutics Bulletin | volume = 42 | issue = 12 | pages = 89–93 | date = December 2004 | pmid = 15587763 | doi = 10.1136/dtb.2004.421289 }}</ref> Between 1993 and 2010, the prescribing of benzodiazepines to individuals with sleep disorders has decreased from 24% to 11% in the US, coinciding with the first release of [[nonbenzodiazepine]]s.<ref name="Kaufmann">{{cite journal | vauthors = Kaufmann CN, Spira AP, Alexander GC, Rutkow L, Mojtabai R | title = Trends in prescribing of sedative-hypnotic medications in the USA: 1993–2010 | journal = Pharmacoepidemiology and Drug Safety | volume = 25 | issue = 6 | pages = 637–45 | date = June 2016 | pmid = 26711081 | pmc = 4889508 | doi = 10.1002/pds.3951 }}</ref>

The [[benzodiazepine]] and [[nonbenzodiazepine]] [[hypnotic]] medications also have several side effects, such as daytime fatigue, motor vehicle crashes and other accidents, cognitive impairments, and falls and fractures. Elderly people are more sensitive to these side effects.<ref>{{cite journal | vauthors = Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE | title = Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits | journal = BMJ | volume = 331 | issue = 7526 | pages = 1169 | date = November 2005 | pmid = 16284208 | pmc = 1285093 | doi = 10.1136/bmj.38623.768588.47 }}</ref> Some benzodiazepines have demonstrated effectiveness in sleep maintenance in the short term but in the longer term benzodiazepines can lead to [[drug tolerance|tolerance]], [[physical dependence]], [[benzodiazepine withdrawal syndrome]] upon discontinuation, and long-term worsening of sleep, especially after consistent usage over long periods. Benzodiazepines, while inducing unconsciousness, actually worsen sleep as – like alcohol – they promote light sleep while decreasing time spent in deep sleep.<ref>{{cite journal | vauthors = Tsoi WF | title = Insomnia: drug treatment | journal = Annals of the Academy of Medicine, Singapore | volume = 20 | issue = 2 | pages = 269–72 | date = March 1991 | pmid = 1679317 }}</ref> A further problem is, with regular use of short-acting sleep aids for insomnia, daytime [[rebound anxiety]] can emerge.<ref>{{cite journal | vauthors = Montplaisir J | title = Treatment of primary insomnia | journal = CMAJ | volume = 163 | issue = 4 | pages = 389–91 | date = August 2000 | pmid = 10976252 | pmc = 80369 }}</ref> Although there is little evidence for benefit of benzodiazepines in insomnia compared to other treatments and evidence of major harm, prescriptions have continued to increase.<ref name="handbook_of_integrative">{{Cite book |vauthors=Carlstedt RA |title=Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research |date=2009 |publisher=Springer |url=https://books.google.com/books?id=4Tkdm1vRFbUC |isbn=978-0-8261-1094-7 |pages=128–30 |access-date=2020-05-12 |archive-date=2020-06-04 |archive-url=https://web.archive.org/web/20200604135538/https://books.google.com/books?id=4Tkdm1vRFbUC%2F |url-status=live }}</ref> This is likely due to their addictive nature, both due to misuse and because – through their rapid action, tolerance and withdrawal they can "trick" insomniacs into thinking they are helping with sleep. There is a general awareness that long-term use of benzodiazepines for insomnia in most people is inappropriate and that a gradual withdrawal is usually beneficial due to the adverse effects associated with the [[long-term use of benzodiazepines]] and is recommended whenever possible.<ref>{{cite book | vauthors =  Lader M, Cardinali DP, Pandi-Perumal SR |title=Sleep and sleep disorders: a neuropsychopharmacological approach |date=2006 |publisher=Landes Bioscience/Eurekah.com |location=Georgetown, Tex. |isbn=978-0-387-27681-6 |page=127 }}</ref><ref name="Authier-">{{cite journal | vauthors = Authier N, Boucher A, Lamaison D, Llorca PM, Descotes J, Eschalier A | title = Second meeting of the French CEIP (Centres d'Evaluation et d'Information sur la Pharmacodépendance). Part II: benzodiazepine withdrawal | journal = Therapie | volume = 64 | issue = 6 | pages = 365–70 | year = 2009 | pmid = 20025839 | doi = 10.2515/therapie/2009051 }}</ref>

Benzodiazepines all bind unselectively to the [[GABAA receptor|GABA<sub>A</sub> receptor]].<ref name="pmid17619935" /> Some theorize that certain benzodiazepines (hypnotic benzodiazepines) have significantly higher activity at the α<sub>1</sub> subunit of the GABA<sub>A</sub> receptor compared to other benzodiazepines (for example, triazolam and temazepam have significantly higher activity at the α<sub>1</sub> subunit compared to alprazolam and diazepam, making them superior sedative-hypnotics&nbsp;– alprazolam and diazepam, in turn, have higher activity at the α<sub>2</sub> subunit compared to triazolam and temazepam, making them superior anxiolytic agents). Modulation of the α<sub>1</sub> subunit is associated with sedation, motor impairment, respiratory depression, amnesia, ataxia, and reinforcing behavior (drug-seeking behavior). Modulation of the α<sub>2</sub> subunit is associated with anxiolytic activity and disinhibition. For this reason, certain benzodiazepines may be better suited to treat insomnia than others.<ref name="Insomnia"/>

==== Z-Drugs ====
[[Nonbenzodiazepine]] or [[Z-drug]] sedative–hypnotic drugs, such as [[zolpidem]], [[zaleplon]], [[zopiclone]], and [[eszopiclone]], are a class of hypnotic medications that are similar to benzodiazepines in their mechanism of action, and indicated for mild to moderate insomnia. Their effectiveness at improving time to sleeping is slight, and they have similar—though potentially less severe—side effect profiles compared to benzodiazepines.<ref>{{cite journal | vauthors = Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN | title = Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration | journal = BMJ | volume = 345 | pages = e8343 | date = December 2012 | pmid = 23248080 | pmc = 3544552 | doi = 10.1136/bmj.e8343 }}</ref> Prescribing of nonbenzodiazepines has seen a general increase since their initial release on the US market in 1992, from 2.3% in 1993 among individuals with sleep disorders to 13.7% in 2010.<ref name="Kaufmann" />

==== Orexin antagonists ====
[[Orexin receptor antagonist]]s are a more recently introduced class of sleep medications and include [[suvorexant]], [[lemborexant]], and [[daridorexant]], all of which are FDA-approved for treatment of insomnia characterized by difficulties with [[sleep onset]] and/or sleep maintenance.<ref name="pmid35043499">{{cite journal | vauthors = Jacobson LH, Hoyer D, de Lecea L | title = Hypocretins (orexins): The ultimate translational neuropeptides | journal = J Intern Med | volume = 291| issue = 5| pages = 533–556| date = January 2022 | pmid = 35043499 | doi = 10.1111/joim.13406 | s2cid = 248119793 | url = }}</ref><ref name="prescribing info">{{cite web |url=http://www.merck.com/product/usa/pi_circulars/b/belsomra/belsomra_pi.pdf |title=Highlights of prescribing information |url-status=live |archive-url=https://web.archive.org/web/20140912065432/http://www.merck.com/product/usa/pi_circulars/b/belsomra/belsomra_pi.pdf |archive-date=12 September 2014 }}</ref> They are oriented towards blocking signals in the brain that stimulate wakefulness, therefore claiming to address insomnia without creating dependence. There are three [[Orexin antagonist|dual orexin receptor (DORA)]] drugs on the market: [[Suvorexant|Belsomra]] ([[Merck & Co.|Merck]]), [[Lemborexant|Dayvigo]] ([[Eisai (company)|Eisai]]) and [[Daridorexant|Quviviq]] ([[Idorsia]]).<ref name="Dunleavy"/>

==== Antipsychotics ====
Certain [[atypical antipsychotic]]s, particularly [[quetiapine]], [[olanzapine]], and [[risperidone]], are used in the treatment of insomnia.<ref name="pmid27544830">{{cite journal | vauthors = Thompson W, Quay TA, Rojas-Fernandez C, Farrell B, Bjerre LM | title = Atypical antipsychotics for insomnia: a systematic review | journal = Sleep Med | volume = 22 | issue = | pages = 13–17 | date = June 2016 | pmid = 27544830 | doi = 10.1016/j.sleep.2016.04.003 | url = }}</ref><ref name="Morin2014">{{cite journal | vauthors = Morin AK | title = Off-label use of atypical antipsychotic agents for treatment of insomnia | journal = Mental Health Clinician | date = 1 March 2014 | volume = 4 | issue = 2 | pages = 65–72 | eissn = 2168-9709 | doi = 10.9740/mhc.n190091 | pmid = | url = | doi-access = free }}</ref> However, while common, the use of antipsychotics for this indication is not recommended as the evidence does not demonstrate a benefit, and the risk of adverse effects is significant.<ref name="pmid27544830" /><ref>{{Citation |author1=American Psychiatric Association |author1-link=American Psychiatric Association |date=September 2013 |title=Five Things Physicians and Patients Should Question |publisher=[[American Psychiatric Association]] |work=[[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |url=http://www.choosingwisely.org/doctor-patient-lists/american-psychiatric-association/ |access-date=30 December 2013 |url-status=live |archive-url=https://web.archive.org/web/20131203174206/http://www.choosingwisely.org/doctor-patient-lists/american-psychiatric-association/ |archive-date=3 December 2013 }}, which cites
* {{cite journal | title = Consensus development conference on antipsychotic drugs and obesity and diabetes | journal = Diabetes Care | volume = 27 | issue = 2 | pages = 596–601 | date = February 2004 | pmid = 14747245 | doi = 10.2337/diacare.27.2.596 | author1 = American Association of Clinical Endocrinologists | author2 = North American Association for the Study of Obesity | doi-access = free }}
* {{cite book | vauthors = Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ, Ewing BA, Motala A, Perry T | chapter = Off-Label Use of Atypical Antipsychotics: An Update | title = AHRQ Comparative Effectiveness Reviews | location = Rockville (MD) | publisher = Agency for Healthcare Research and Quality (US)| date = Sep 2011 | pmid = 22132426 }}
* {{cite journal | vauthors = Nasrallah HA | title = Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles | journal = Molecular Psychiatry | volume = 13 | issue = 1 | pages = 27–35 | date = January 2008 | pmid = 17848919 | doi = 10.1038/sj.mp.4002066 | s2cid = 205678886 }}</ref><ref>{{cite journal | vauthors = Coe HV, Hong IS | title = Safety of low doses of quetiapine when used for insomnia | journal = The Annals of Pharmacotherapy | volume = 46 | issue = 5 | pages = 718–722 | date = May 2012 | pmid = 22510671 | doi = 10.1345/aph.1Q697 | s2cid = 9888209 }}</ref><ref name="Off-Label Use">{{cite book |title=Off-Label Use of Atypical Antipsychotics: An Update |vauthors=Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ |publisher=Agency for Healthcare Research and Quality |year=2011 |series=Comparative Effectiveness Reviews, No. 43 |location=Rockville |pmid=22973576}}</ref> A major 2022 systematic review and network meta-analysis of medications for insomnia in adults found that quetiapine did not demonstrate any short-term benefits for insomnia.<ref name="pmid35843245">{{cite journal |vauthors=De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A |date=July 2022 |title=Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis |url= |journal=Lancet |volume=400 |issue=10347 |pages=170–184 |doi=10.1016/S0140-6736(22)00878-9 |pmid=35843245 |s2cid=250536370|doi-access=free |hdl=11380/1288245 |hdl-access=free }}</ref> Some of the more serious adverse effects may also occur at the low doses used, such as [[dyslipidemia]] and [[neutropenia]].<ref>{{cite journal | vauthors = Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, Beck K, Natesan S, Efthimiou O, Cipriani A, Howes OD | title = Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis | journal = The Lancet. Psychiatry | volume = 7 | issue = 1 | pages = 64–77 | date = January 2020 | pmid = 31860457 | pmc = 7029416 | doi = 10.1016/s2215-0366(19)30416-x }}</ref><ref>{{cite journal | vauthors = Yoshida K, Takeuchi H | title = Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia | journal = Behavioural Brain Research | volume = 402 | pages = 113098 | date = March 2021 | pmid = 33417992 | doi = 10.1016/j.bbr.2020.113098 | s2cid = 230507941 | doi-access = free }}</ref> Such concerns of risks at low doses are supported by Danish observational studies that showed an association of use of low-dose quetiapine (excluding prescriptions filled for tablet strengths >50&nbsp;mg) with an increased risk of major cardiovascular events as compared to use of [[Z-drugs]], with most of the risk being driven by cardiovascular death.<ref>{{cite journal | vauthors = Højlund M, Andersen K, Ernst MT, Correll CU, Hallas J | title = Use of low-dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator-controlled cohort study | journal = World Psychiatry | volume = 21 | issue = 3 | pages = 444–451 | date = October 2022 | pmid = 36073694 | pmc = 9453914 | doi = 10.1002/wps.21010 }}</ref> Laboratory data from an unpublished analysis of the same cohort also support the lack of dose-dependency of metabolic side effects, as new use of low-dose quetiapine was associated with a risk of increased fasting triglycerides at one-year follow-up.<ref>{{Cite thesis |date=2022-09-12 |title=Low-dose Quetiapine: Utilization and Cardiometabolic Risk |url=https://portal.findresearcher.sdu.dk/en/publications/low-dose-quetiapine-utilization-and-cardiometabolic-risk |language=English |doi=10.21996/mr3m-1783 |vauthors=Højlund M |publisher=Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet |access-date=2022-10-18 |archive-date=2022-10-18 |archive-url=https://web.archive.org/web/20221018082542/https://portal.findresearcher.sdu.dk/en/publications/low-dose-quetiapine-utilization-and-cardiometabolic-risk |url-status=live }}</ref> Concerns regarding side effects are greater in the elderly.<ref name="Conn 271–287">{{cite journal |vauthors=Conn DK, Madan R |year=2006 |title=Use of sleep-promoting medications in nursing home residents: risks versus benefits |journal=Drugs & Aging |volume=23 |issue=4 |pages=271–87 |doi=10.2165/00002512-200623040-00001 |pmid=16732687 |s2cid=38394552}}</ref>

==== Other sedatives ====
[[Gabapentinoid]]s like [[gabapentin]] and [[pregabalin]] have sleep-promoting effects but are not commonly used for the treatment of insomnia.<ref name="pmid29487083">{{cite journal|author3-link=Gabriella Gobbi | vauthors = Atkin T, Comai S, Gobbi G | title = Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery | journal = Pharmacol Rev | volume = 70 | issue = 2 | pages = 197–245 | date = April 2018 | pmid = 29487083 | doi = 10.1124/pr.117.014381 | s2cid = 3578916 | url = | doi-access = free }}</ref> Gabapentin is not effective in helping alcohol related insomnia.<ref name="NIHR Evidence_2022">{{Cite journal |date=17 October 2022 |title=Review finds little evidence to support gabapentinoid use in bipolar disorder or insomnia |url=https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_54173 |s2cid=252983016 |access-date=21 November 2022 |archive-date=27 November 2022 |archive-url=https://web.archive.org/web/20221127080508/https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |url-status=live }}</ref><ref name="Hong_2022">{{cite journal |vauthors=Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, Harrison PJ, Cipriani A |date=March 2022 |title=Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale |journal=Molecular Psychiatry |volume=27 |issue=3 |pages=1339–1349 |doi=10.1038/s41380-021-01386-6 |pmc=9095464 |pmid=34819636}}</ref>

[[Barbiturate]]s, while once used, are no longer recommended for insomnia due to the risk of addiction and other side effects.<ref>{{cite book| vauthors = Aschenbrenner DS, Venable SJ |title=Drug Therapy in Nursing |date=2009 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-6587-9 |page=[https://archive.org/details/studyguidetoacco0000asch/page/277 277]|url=https://archive.org/details/studyguidetoacco0000asch|url-access=registration|language=en}}</ref>

====Comparative effectiveness====
Medications for the treatment of insomnia have a wide range of [[effect size]]s.<ref name="pmid35843245" /> When comparing drugs such as [[benzodiazepine]]s, [[Z-drug]]s, sedative [[antidepressant]]s and [[antihistamine]]s, [[quetiapine]], [[orexin receptor antagonist]]s, and [[melatonin receptor agonist]]s, the orexin antagonist [[lemborexant]] and the Z-drug [[eszopiclone]] had the best profiles overall in terms of [[efficacy]], [[tolerability]], and [[acceptability]].<ref name="pmid35843245" />