Editing Hypnotic

{{Short description|Drug whose use induces sleep}}
{{About|the class of prescription medicines|the state of mind|Hypnosis|other uses}}
{{Redirect|Sleeping pills|the 2003 film|Sleeping Pills (film)}}
{{See also|Sedative}}
[[File:Stilnoct2.JPG|thumb|alt=refer to caption|[[Zolpidem]], a common but potent sedative–hypnotic drug. Used for severe insomnia.]]

A '''hypnotic''' (from [[Ancient Greek|Greek]] ''Hypnos'', sleep<ref>{{Cite web|title=Definition of HYPNOTIC|url=https://www.merriam-webster.com/dictionary/hypnotic|access-date=2021-09-27|website=www.merriam-webster.com|language=en}}</ref>), also known as a '''somnifacient''' or '''soporific''', and commonly known as '''sleeping pills''', are a class of [[psychoactive drug]]s whose primary function is to [[sleep induction|induce sleep]]<ref name="urlDorlands Medical Dictionary:hypnotic">{{cite web |url= http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/four/000051451.htm |title=Dorlands Medical Dictionary:hypnotic |website=Mercksource.com |archive-url=https://web.archive.org/web/20081211091401/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=%2Fppdocs%2Fus%2Fcommon%2Fdorlands%2Fdorland%2Ffour%2F000051451.htm |archive-date=2008-12-11 |url-status=dead }}</ref> and to treat [[insomnia]] (sleeplessness).

This group of drugs is related to [[sedative]]s''. ''Whereas the term sedative describes drugs that serve to calm or [[Anxiolytic|relieve anxiety]], the term hypnotic generally describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from [[anxiolysis]] to [[loss of consciousness]]), they are often referred to collectively as '''sedative–hypnotic''' drugs.<ref name="Pharmacologic Basis of Therapeutics">{{cite book| vauthors = Brunton LL, Parker K, Lazo KL, Buxton I, Blumenthal D |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics |publisher=The McGraw-Hill Companies, Inc. |year=2006 |edition=11th |chapter-url=http://accessmedicine.mhmedical.com/content.aspx?bookid=374&sectionid=41266223 |chapter=17: Hypnotics and Sedatives |isbn=978-0-07-146804-6 |access-date=2014-02-06}}</ref>

Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries.<ref name="npsnews">{{cite web |url=http://www.nps.org.au/health_professionals/publications/nps_news/current/nps_news_67 |title=NPS News 67: Addressing hypnotic medicines use in primary care |author=National Prescribing Service |date=2 February 2010 |access-date=19 March 2010 |url-status=dead |archive-url=https://web.archive.org/web/20110222130542/http://www.nps.org.au/health_professionals/publications/nps_news/current/nps_news_67 |archive-date=22 February 2011 }}</ref> Many hypnotic drugs are habit-forming and—due to many factors known to disturb the human sleep pattern—a physician may instead recommend changes in the environment before and during sleep, better [[sleep hygiene]], the avoidance of caffeine and [[alcohol (drug)|alcohol]] or other stimulating substances, or behavioral interventions such as [[cognitive behavioral therapy for insomnia]] (CBT-I), before prescribing medication for sleep. When prescribed, hypnotic medication should be used for the shortest period of time necessary.<ref>{{cite journal | vauthors = Mendels J | title = Criteria for selection of appropriate benzodiazepine hypnotic therapy | journal = The Journal of Clinical Psychiatry | volume = 52 | issue = Suppl | pages = 42–46 | date = September 1991 | pmid = 1680126 | series = 52 }}</ref>

Among individuals with sleep disorders, 13.7% are taking or prescribed [[nonbenzodiazepine]]s (Z-drugs), while 10.8% are taking [[benzodiazepine]]s, as of 2010, in the USA.<ref>{{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 = 637–645 | date = June 2016 | pmid = 26711081 | pmc = 4889508 | doi = 10.1002/pds.3951 }}</ref> Early classes of drugs, such as [[barbiturate]]s, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable—unless used to treat [[night terror]]s or [[sleepwalking]].<ref>{{cite book| vauthors = Gelder M, Mayou R, Geddes J |year=2005 |title=Psychiatry |edition=3rd |place=New York |publisher=Oxford |page=238}}</ref> Elderly people are more sensitive to potential side effects of daytime fatigue and [[cognitive impairment]], and a [[meta-analysis]] found that the risks generally outweigh any marginal benefits of hypnotics in the elderly.<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> A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs have adverse effects, such as [[substance dependence|dependence]] and accidents, and that optimal treatment uses the lowest effective dose for the shortest therapeutic time, with gradual discontinuation to improve health without worsening of sleep.<ref>{{cite journal | vauthors = <!--none listed--> | 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 | s2cid = 40188442 }}</ref>

Falling outside the above-mentioned categories, the neurohormone [[melatonin (medication)|melatonin]] and its analogues (e.g., [[ramelteon]]) serve a hypnotic function.<ref>{{cite journal | vauthors = Zhdanova IV | title = Melatonin as a hypnotic: pro | journal = Sleep Medicine Reviews | volume = 9 | issue = 1 | pages = 51–65 | date = February 2005 | pmid = 15649738 | doi = 10.1016/j.smrv.2004.04.003 }}</ref>

==Types==
===Barbiturates===
{{Main|Barbiturate}}

[[Barbiturate]]s are drugs that act as [[central nervous system]] [[depressant]]s, and can therefore produce a broad spectrum of effects, from mild [[sedation]] to total [[anesthesia]]. They are also effective as [[anxiolytic]]s, hypnotics, and [[anticonvulsant]] effects; however, these effects are somewhat weak, preventing barbiturates from being used in [[surgery]] in the absence of other analgesics. They have dependence liability, both [[physical dependence|physical]] and [[psychological dependence|psychological]]. Barbiturates have now largely been replaced by [[benzodiazepine]]s in routine medical practice&nbsp;– such as in the treatment of anxiety and insomnia&nbsp;– mainly because benzodiazepines are significantly less dangerous in [[drug overdose|overdose]]. However, barbiturates are still used in general anesthesia, for [[epilepsy]], and for [[assisted suicide]]. Barbiturates are derivatives of [[barbituric acid]].

The principal [[mechanism of action]] of barbiturates is believed to be [[positive allosteric modulator|positive allosteric modulation]] of [[GABAA|GABA<sub>A</sub>]] receptors.<ref>{{cite journal | vauthors = Löscher W, Rogawski MA | title = How theories evolved concerning the mechanism of action of barbiturates | journal = Epilepsia | volume = 53 | issue = Suppl 8 | pages = 12–25 | date = December 2012 | pmid = 23205959 | doi = 10.1111/epi.12025 | s2cid = 4675696 | doi-access = free }}</ref>

Examples include [[amobarbital]], [[pentobarbital]], [[phenobarbital]], [[secobarbital]], and [[sodium thiopental]].

===Quinazolinones===
{{main|Quinazolinone}}

{{See also|Methaqualone}}<!--All other articles are currently stubs. This is the only substantial article we have. (February 2014)-->

[[Quinazolinone]]s are also a class of drugs that function as hypnotics/sedatives that contain a 4-quinazolinone core. Their use has also been proposed in the treatment of [[cancer]].<ref name="pmid17172404">{{cite journal | vauthors = Chen K, Wang K, Kirichian AM, Al Aowad AF, Iyer LK, Adelstein SJ, Kassis AI | title = In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and therapy | journal = Molecular Cancer Therapeutics | volume = 5 | issue = 12 | pages = 3001–3013 | date = December 2006 | pmid = 17172404 | doi = 10.1158/1535-7163.MCT-06-0465 | doi-access = free }}</ref>

Examples of quinazolinones include [[cloroqualone]], [[diproqualone]], [[etaqualone]] (Aolan, Athinazone, Ethinazone), [[mebroqualone]], [[Afloqualone]] (Arofuto), [[mecloqualone]] (Nubarene, Casfen), and [[methaqualone]] (Quaalude).

===Benzodiazepines===
{{main|Benzodiazepine#Insomnia}}

{{See also|List of benzodiazepines}}

[[Benzodiazepine]]s can be useful for short-term treatment of insomnia. Their use beyond 2 to 4 weeks is not recommended due to the risk of dependence. It is preferred that benzodiazepines be taken intermittently and at the lowest effective dose. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging sleep time, and reducing wakefulness.<ref name="nice-hypnotics">{{cite web|title=Technology Appraisal Guidance 77. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia |url=http://www.nice.org.uk/nicemedia/pdf/TA077fullguidance.pdf |publisher=National Institute for Clinical Excellence |date=April 2004 |access-date=2009-07-26 |url-status=dead |archive-url=https://web.archive.org/web/20081203063917/http://www.nice.org.uk/nicemedia/pdf/TA077fullguidance.pdf |archive-date=2008-12-03 }}</ref><ref name="pmid17853625">{{cite journal | vauthors = Ramakrishnan K, Scheid DC | title = Treatment options for insomnia | journal = American Family Physician | volume = 76 | issue = 4 | pages = 517–526 | date = August 2007 | pmid = 17853625 | url = http://www.aafp.org/afp/2007/0815/p517.html }}</ref> Like [[Alcohol (drug)|alcohol]], benzodiazepines are commonly used to treat insomnia in the short-term (both prescribed and self-medicated), but worsen sleep in the long-term. While benzodiazepines can put people to sleep (i.e., inhibit NREM stage 1 and 2 sleep), while asleep, the drugs disrupt [[sleep architecture]] by decreasing sleep time, delaying time to REM sleep, and decreasing deep [[slow-wave sleep]] (the most restorative part of sleep for both energy and mood).<ref>{{cite journal | vauthors = Ashton H | title = The diagnosis and management of benzodiazepine dependence | journal = Current Opinion in Psychiatry | volume = 18 | issue = 3 | pages = 249–255 | date = May 2005 | pmid = 16639148 | doi = 10.1097/01.yco.0000165594.60434.84 | s2cid = 1709063 }}</ref><ref>{{cite journal | vauthors = Morin CM, Bélanger L, Bastien C, Vallières A | title = Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse | journal = Behaviour Research and Therapy | volume = 43 | issue = 1 | pages = 1–14 | date = January 2005 | pmid = 15531349 | doi = 10.1016/j.brat.2003.12.002 }}</ref><ref>{{cite journal | vauthors = Poyares D, Guilleminault C, Ohayon MM, Tufik S | title = Chronic benzodiazepine usage and withdrawal in insomnia patients | journal = Journal of Psychiatric Research | volume = 38 | issue = 3 | pages = 327–334 | date = 2004-06-01 | pmid = 15003439 | doi = 10.1016/j.jpsychires.2003.10.003 }}</ref>

Other drawbacks of hypnotics, including benzodiazepines, are possible [[Drug tolerance|tolerance]] to their effects, [[rebound insomnia]], and reduced slow-wave sleep and a withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation.<ref name="handbook_of_integrative">{{Cite book| vauthors = Maiuro RD |title=Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research |date=13 December 2009 |publisher=Springer Publishing Company |url=https://books.google.com/books?id=4Tkdm1vRFbUC |isbn=978-0-8261-1094-7 |pages=128–30}}</ref><ref name="ahrq" /> The list of benzodiazepines approved for the treatment of insomnia is similar among most countries, but which benzodiazepines are officially designated as first-line hypnotics prescribed for the treatment of insomnia can vary distinctly between countries.<ref name="pmid17853625" /> Longer-acting benzodiazepines, such as [[nitrazepam]] and [[diazepam]], have residual effects that may persist into the next day and are, in general, not recommended.<ref name="nice-hypnotics" />

It is not clear whether the newer [[nonbenzodiazepine]] (Z-drug) hypnotics are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar.<ref name="nice-hypnotics" /><ref name="ahrq" /> According to the US [[Agency for Healthcare Research and Quality]], indirect comparison indicates that side effects from benzodiazepines may be about twice as frequent as from nonbenzodiazepines.<ref name="ahrq">{{cite journal | vauthors = Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M | display-authors = 6 | title = Manifestations and management of chronic insomnia in adults | journal = Evidence Report/Technology Assessment | issue = 125 | pages = 1–10 | date = June 2005 | pmid = 15989374 | doi = 10.1037/e439752005-001 | publisher = Agency for Healthcare Research and Quality | pmc = 4781279 }}</ref> Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia.<ref name="pmid17853625" /> However, the UK [[National Institute for Health and Clinical Excellence]] (NICE) did not find any convincing evidence in favor of Z-drugs. A NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines. There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing the hypnotic based on cost and the patient's preference.<ref name="nice-hypnotics" />

Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed to be effective.<ref name="AGSfive">{{cite web|author1=American Geriatrics Society |author1-link = American Geriatrics Society |title=Five Things Physicians and Patients Should Question |publisher=American Geriatrics Society |work=[[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |url=http://www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society/ |access-date=August 1, 2013}}, which cites
*{{cite journal | vauthors = Finkle WD, Der JS, Greenland S, Adams JL, Ridgeway G, Blaschke T, Wang Z, Dell RM, VanRiper KB | display-authors = 6 | title = Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults | journal = Journal of the American Geriatrics Society | volume = 59 | issue = 10 | pages = 1883–1890 | date = October 2011 | pmid = 22091502 | doi = 10.1111/j.1532-5415.2011.03591.x | s2cid = 23523742 }}
*{{cite journal | vauthors = Allain H, Bentué-Ferrer D, Polard E, Akwa Y, Patat A | title = Postural instability and consequent falls and hip fractures associated with use of hypnotics in the elderly: a comparative review | journal = Drugs & Aging | volume = 22 | issue = 9 | pages = 749–765 | year = 2005 | pmid = 16156679 | doi = 10.2165/00002512-200522090-00004 | s2cid = 9296501 }}
*{{cite journal | title = American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults | journal = Journal of the American Geriatrics Society | volume = 60 | issue = 4 | pages = 616–631 | date = April 2012 | pmid = 22376048 | pmc = 3571677 | doi = 10.1111/j.1532-5415.2012.03923.x | author1 = American Geriatrics Society 2012 Beers Criteria Update Expert Panel }}</ref> When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence which shows twice the incidence of [[traffic collisions]] among driving patients, as well as falls and hip fracture for all older patients.<ref name="npsnews" /><ref name="AGSfive" />

Their [[mechanism of action]] is primarily at [[GABAA receptor|GABA<sub>A</sub> receptors]].<ref name="isbn0-12-088397-X">{{cite book| vauthors = Olsen RW, Betz H | veditors = Siegel GJ, Albers RW, Brady S, Price DD |title=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |edition=7th |publisher=Elsevier |year=2006 |pages=291–302 |chapter=GABA and glycine |isbn=978-0-12-088397-4}}</ref>

===Nonbenzodiazepines===
{{Main|Nonbenzodiazepines}}

Nonbenzodiazepines (Z-drugs) are a class of [[psychoactive drug]]s that are "benzodiazepine-like" in nature. Nonbenzodiazepine [[pharmacodynamics]] are almost entirely the same as benzodiazepine drugs, and therefore entail similar benefits, side effects, and risks. Nonbenzodiazepines, however, have dissimilar or different chemical structures, and are unrelated to benzodiazepines on a molecular level.<ref name="pmid9640488a">{{cite journal |vauthors=Wagner J, Wagner ML, Hening WA |date=June 1998 |title=Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia |journal=The Annals of Pharmacotherapy |volume=32 |issue=6 |pages=680–691 |doi=10.1345/aph.17111 |pmid=9640488 |s2cid=34250754}}</ref><ref>{{cite journal | vauthors = Siriwardena AN, Qureshi Z, Gibson S, Collier S, Latham M | title = GPs' attitudes to benzodiazepine and 'Z-drug' prescribing: a barrier to implementation of evidence and guidance on hypnotics | journal = The British Journal of General Practice | volume = 56 | issue = 533 | pages = 964–967 | date = December 2006 | pmid = 17132386 | pmc = 1934058 }}</ref>

Examples include [[zopiclone]] (Imovane), [[eszopiclone]] (Lunesta), [[zaleplon]] (Sonata), and [[zolpidem]] (Ambien). Since the generic names of all drugs of this type start with ''Z'', they are often referred to as ''Z-drugs''.<ref>Ryba, N.; Rainess, R. Z-drugs and Falls: A Focused Review of the Literature. The Senior Care Pharmacist 2020, 35 (12), 549-554. DOI: 10.4140/tcp.n.2020.549.</ref>

Research on nonbenzodiazepines is new and conflicting. A review by a team of researchers suggests the use of these drugs for people who have trouble falling asleep (but not staying asleep),<ref group="note">Because the drugs have a shorter [[elimination half life]] they are metabolized more quickly: nonbenzodiazepines zaleplon and zolpidem have a half-life of 1 and 2 hours (respectively); for comparison, the benzodiazepine clonazepam has a half-life of about 30 hours. This makes the drug suitable for sleep-onset difficulty, but the team noted sustained sleep efficacy was unclear.</ref> as next-day impairments were minimal.<ref name="pmid15746509">{{cite journal | vauthors = Benca RM | title = Diagnosis and treatment of chronic insomnia: a review | journal = Psychiatric Services | volume = 56 | issue = 3 | pages = 332–343 | date = March 2005 | pmid = 15746509 | doi = 10.1176/appi.ps.56.3.332 | quote = Evidence for the utility of currently available nonbenzodiazepine hypnotics points to their primary efficacy as sleep-onset, rather than as sleep-maintenance, agents. Once again, longer-term randomized, double-blind, controlled studies that demonstrate the efficacy of these agents have not been performed, but safety over the longer term has been demonstrated in open-label studies, with minimal evidence of rebound phenomena. By comparison with benzodiazepines, there has been less evidence of subjective and objective next-day residual effects associated with zolpidem or subjective next-day impairment with zaleplon, even when the latter has been delivered in the middle of the night. }}</ref> The team noted that the safety of these drugs had been established, but called for more research into their long-term effectiveness in treating insomnia. Other evidence suggests that [[drug tolerance|tolerance]] to nonbenzodiazepines may be slower to develop than with benzodiazepines.{{failed verification|date=February 2014}} A different team was more skeptical, finding little benefit over benzodiazepines.<ref name="pmid9640488b">{{cite journal | vauthors = Wagner J, Wagner ML, Hening WA | title = Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia | journal = The Annals of Pharmacotherapy | volume = 32 | issue = 6 | pages = 680–691 | date = June 1998 | pmid = 9640488 | doi = 10.1345/aph.17111 | quote = New developments in benzodiazepine receptor pharmacology have introduced novel nonbenzodiazepine hypnotics that provide comparable efficacy to benzodiazepines. Although they may possess theoretical advantages over benzodiazepines based on their unique pharmacologic profiles, they offer few, if any, significant advantages in terms of adverse effects. | s2cid = 34250754 }}</ref>

=== Melatonin/melatonin receptor agonists ===
[[Melatonin (medication)|Melatonin]], the hormone produced in the [[pineal gland]] in the brain and secreted in dim light and darkness, among its other functions, promotes sleep in [[Diurnality|diurnal]] mammals.<ref>{{cite journal | vauthors = Arendt J, Skene DJ | title = Melatonin as a chronobiotic | journal = Sleep Medicine Reviews | volume = 9 | issue = 1 | pages = 25–39 | date = February 2005 | pmid = 15649736 | doi = 10.1016/j.smrv.2004.05.002 }}</ref> It activates both melatonin receptors MT<sub>1</sub> and MT<sub>2</sub> to produce beneficial effects on sleep, therefore being used exogenously for mild insomnia.<ref>{{Cite journal |last1=Liu |first1=Jiabei |last2=Clough |first2=Shannon J. |last3=Hutchinson |first3=Anthony J. |last4=Adamah-Biassi |first4=Ekue B. |last5=Popovska-Gorevski |first5=Marina |last6=Dubocovich |first6=Margarita L. |date=2016 |title=MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective |journal=Annual Review of Pharmacology and Toxicology |volume=56 |pages=361–383 |doi=10.1146/annurev-pharmtox-010814-124742 |issn=1545-4304 |pmc=5091650 |pmid=26514204}}</ref> A small improvement in sleep onset and total sleep time by using melatonin has been shown in recent systematic reviews.<ref>{{Cite journal |last1=Low |first1=Tian Ling |last2=Choo |first2=Faith Nadine |last3=Tan |first3=Shian Ming |year=2020 |title=The efficacy of melatonin and melatonin agonists in insomnia - An umbrella review |url=https://pubmed.ncbi.nlm.nih.gov/31715492/ |journal=Journal of Psychiatric Research |volume=121 |pages=10–23 |doi=10.1016/j.jpsychires.2019.10.022 |issn=1879-1379 |pmid=31715492 |s2cid=207949129}}</ref>

[[Synthetic compound|Synthetic]] [[structural analog|analogue]]s of melatonin, or [[melatonin receptor agonist]]s, have also been made. Among these, [[ramelteon]] and [[tasimelteon]] are used for sleep disorders. [[Agomelatine]] is an antidepressant of this class, with some studies also reporting an effect on sleep.<ref name="Williams2016">{{cite journal | vauthors = Williams WP, McLin DE, Dressman MA, Neubauer DN | title = Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders | journal = Pharmacotherapy | volume = 36 | issue = 9 | pages = 1028–41 | date = September 2016 | pmid = 27500861 | pmc = 5108473 | doi = 10.1002/phar.1822 | url = }}</ref>

=== Antihistamines ===
{{Main|H1 antagonist}}
[[Antihistamine]]s, also known as H<sub>1</sub> antagonists, are a class of drugs that inhibit action at H<sub>1</sub> receptors. They are clinically used to alleviate allergic reactions including [[allergic rhinitis]], [[allergic conjunctivitis]], and [[urticaria]], which are mediated by [[histamine]].{{Citation needed|date=March 2025}} First-generation antihistamines, such as [[doxylamine]] and [[diphenhydramine]], often cause sedation as a side effect, which can be utilized to treat insomnia. Some antihistamines, such as doxylamine, are available for purchase [[over-the-counter]] (OTC) in some countries and can be used for the occasional relief of insomnia.<ref>{{Cite journal |last1=Culpepper |first1=Larry |last2=Wingertzahn |first2=Mark A. |date=2015 |title=Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety |journal=The Primary Care Companion for CNS Disorders |volume=17 |issue=6 |doi=10.4088/PCC.15r01798 |issn=2155-7772 |pmc=4805417 |pmid=27057416}}</ref> Low-dose [[doxepin]] is approved by the FDA for the treatment of insomnia.<ref name=":1">{{Cite web |title=Pharmacotherapy for insomnia in adults |url=https://www.uptodate.com/contents/pharmacotherapy-for-insomnia-in-adults |access-date=2023-03-13 |website=www.uptodate.com}}</ref> Second generation of antihistamines such as [[cetirizine]] and [[loratadine]] have a much less sedating effect than the first ones with a much lower degree of crossing the [[blood–brain barrier]].<ref>{{Cite journal |last1=Slater |first1=J. W. |last2=Zechnich |first2=A. D. |last3=Haxby |first3=D. G. |year=1999 |title=Second-generation antihistamines: a comparative review |url=https://pubmed.ncbi.nlm.nih.gov/9951950/ |journal=Drugs |volume=57 |issue=1 |pages=31–47 |doi=10.2165/00003495-199957010-00004 |issn=0012-6667 |pmid=9951950 |s2cid=46984477}}</ref>

In common use, the term ''antihistamine'' refers only to compounds that inhibit action at the H<sub>1</sub> receptor.{{Citation needed|date=March 2025}}

Clinically, H<sub>1</sub> antagonists are used to treat certain [[Allergy|allergies]]. Sedation is a common side effect, and some H<sub>1</sub> antagonists, such as [[diphenhydramine]] and doxylamine, are also used to treat insomnia.{{Citation needed|date=March 2025}}

=== Orexin antagonists ===
[[Dual orexin receptor antagonist]]s are drugs that block the orexin receptors [[Hypocretin (orexin) receptor 1|OX<sub>1</sub>]] and [[Hypocretin (orexin) receptor 2|OX<sub>2</sub>]], hence reducing the wakeful effect of the [[orexin system]] and inducing sleep.<ref>{{Cite journal |last1=Mieda |first1=Michihiro |last2=Tsujino |first2=Natsuko |last3=Sakurai |first3=Takeshi |date=2013 |title=Differential roles of orexin receptors in the regulation of sleep/wakefulness |journal=Frontiers in Endocrinology |volume=4 |pages=57 |doi=10.3389/fendo.2013.00057 |issn=1664-2392 |pmc=3656340 |pmid=23730297 |doi-access=free}}</ref> Orexin antagonists [[daridorexant]], [[lemborexant]], and [[suvorexant]] have been shown in studies to improve sleep onset and sleep quality.<ref>{{Cite journal |last1=Kuriyama |first1=Akira |last2=Tabata |first2=Hiromitsu |year=2017 |title=Suvorexant for the treatment of primary insomnia: A systematic review and meta-analysis |url=https://pubmed.ncbi.nlm.nih.gov/28365447/ |journal=Sleep Medicine Reviews |volume=35 |pages=1–7 |doi=10.1016/j.smrv.2016.09.004 |issn=1532-2955 |pmid=28365447}}</ref><ref>{{Cite journal |last1=Mignot |first1=Emmanuel |last2=Mayleben |first2=David |last3=Fietze |first3=Ingo |last4=Leger |first4=Damien |last5=Zammit |first5=Gary |last6=Bassetti |first6=Claudio L. A. |last7=Pain |first7=Scott |last8=Kinter |first8=Dalma Seboek |last9=Roth |first9=Thomas |last10=investigators |year=2022 |title=Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials |url=https://pubmed.ncbi.nlm.nih.gov/35065036/ |journal=The Lancet. Neurology |volume=21 |issue=2 |pages=125–139 |doi=10.1016/S1474-4422(21)00436-1 |issn=1474-4465 |pmid=35065036 |s2cid=246054876}}</ref>

=== Others ===

====Antidepressants====
Some [[antidepressant]]s have sedating effects.

Examples include:

; [[Serotonin antagonist and reuptake inhibitor]]s
* [[Trazodone]]<ref>{{cite journal | vauthors = Haria M, Fitton A, McTavish D | title = Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders | journal = Drugs & Aging | volume = 4 | issue = 4 | pages = 331–355 | date = April 1994 | pmid = 8019056 | doi = 10.2165/00002512-199404040-00006 | s2cid = 265772823 }}</ref>
; [[Tricyclic antidepressant]]s
* [[Amitriptyline]]<ref>{{cite web|title=Levate (amitriptyline), dosing, indications, interactions, adverse effects, and more |work=Medscape Reference |publisher=WebMD |access-date=1 December 2013 |url=http://reference.medscape.com/drug/levate-amitriptyline-342936#showall}}</ref>
* [[Doxepin]]<ref>{{cite journal | vauthors = Hajak G, Rodenbeck A, Voderholzer U, Riemann D, Cohrs S, Hohagen F, Berger M, Rüther E | display-authors = 6 | title = Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study | journal = The Journal of Clinical Psychiatry | volume = 62 | issue = 6 | pages = 453–463 | date = June 2001 | pmid = 11465523 | doi = 10.4088/JCP.v62n0609 }}</ref>
* [[Trimipramine]]<ref>
{{cite book | isbn         = 978-0-85711-084-8 | title         = British National Formulary (BNF) | last1         = Joint Formulary Committee | year         = 2013 | publisher         = Pharmaceutical Press | location         = London, UK | edition         = 65 | url-access         = registration | url         = https://archive.org/details/bnf65britishnati0000unse }}
{{page needed|date=February 2014}}</ref>
; [[Tetracyclic antidepressant]]s
* [[Mianserin]]<ref>{{cite journal | vauthors = Wakeling A | title = Efficacy and side effects of mianserin, a tetracyclic antidepressant | journal = Postgraduate Medical Journal | volume = 59 | issue = 690 | pages = 229–231 | date = April 1983 | pmid = 6346303 | pmc = 2417496 | doi = 10.1136/pgmj.59.690.229 }}</ref>
* [[Mirtazapine]]<ref>{{cite journal | vauthors = Hartmann PM | title = Mirtazapine: a newer antidepressant | journal = American Family Physician | volume = 59 | issue = 1 | pages = 159–161 | date = January 1999 | pmid = 9917581 }}</ref><ref>{{cite journal | vauthors = Jindal RD | title = Insomnia in patients with depression: some pathophysiological and treatment considerations | journal = CNS Drugs | volume = 23 | issue = 4 | pages = 309–329 | year = 2009 | pmid = 19374460 | doi = 10.2165/00023210-200923040-00004 | s2cid = 22052011 }}</ref>

====Antipsychotics====
While some of these drugs are frequently prescribed for insomnia, such use is not recommended unless the insomnia is due to an underlying mental health condition treatable by [[antipsychotic]]s as the risks frequently outweigh the benefits.<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><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> Some of the more serious adverse effects have been observed to occur at the low doses used for this off-label prescribing, such as [[dyslipidemia]] and [[neutropenia]],<ref>{{Cite thesis | vauthors = Højlund M | degree = Ph.D. | publisher = University of Southern Denmark |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}}</ref><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><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 | display-authors = 6 | 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> and a recent network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine had not demonstrated any short-term benefits in sleep quality.<ref>{{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 | display-authors = 6 | 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 | language = English | journal = Lancet | volume = 400 | issue = 10347 | pages = 170–184 | date = July 2022 | pmid = 35843245 | doi = 10.1016/S0140-6736(22)00878-9 | s2cid = 250536370 | doi-access = free | hdl = 11380/1288245 | hdl-access = free }}</ref> Examples of [[antipsychotic]]s with sedation as a side effect that are occasionally used for insomnia:<ref>{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | display-authors = 6 | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref>

; [[First-generation antipsychotic|First-generation]]
* [[Chlorpromazine]]
; [[Second-generation antipsychotic|Second-generation]]
* [[Clozapine]]
* [[Olanzapine]]
* [[Quetiapine]]
* [[Risperidone]]
* [[Zotepine]]
* [[Ziprasidone]]

====Miscellaneous drugs====
{{Unreferenced section|date=March 2025}}
; [[Alpha-adrenergic agonist]]
* [[Clonidine]]
* [[Guanfacine]]

; [[Cannabinoid]]s
* [[Cannabidiol]]
* [[Tetrahydrocannabinol]]

; [[Gabapentinoid]]s
* [[Gabapentin]]
* [[Pregabalin]]
* [[Phenibut]]
==History==
[[File:A corrupt old man tries to seduce a woman by urging Wellcome L0034228.jpg|thumb|''Le Vieux [[seducer|Séducteur]]'' by {{Interlanguage link multi|Charles Motte|fr}}.<br />(A corrupt old man tries to seduce a woman by urging her to take a hypnotic draught in her drink)]]

'''Hypnotica''' was a class of somniferous drugs and substances tested in medicine of the 1890s and later. These include [[Ethyl carbamate|urethan]], [[1,1-Diethoxyethane|acetal]], [[methylal]], [[sulfonal]], [[paraldehyde]], [[tert-Amyl alcohol|amylenhydrate]], [[Acetophenone|hypnon]], chloralurethan, ohloralamid, or chloralimid.<ref>Pacific Record of Medicine and Surgery - Volume 5 - Page 36 1890</ref>

Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Treatment for insomnia in psychiatry dates back to 1869, when [[chloral hydrate]] was first used as a soporific.<ref name="isbn0-19-517668-5">{{cite book |title=A Historical Dictionary of Psychiatry |vauthors=Shorter E |publisher=Oxford University Press |year=2005 |isbn=978-0-19-517668-1 |pages=41–2 |chapter=Benzodiazepines |access-date=2014-02-06 |chapter-url=https://books.google.com/books?id=M49pEDoEpl0C&pg=PA41}}</ref> [[Barbiturate]]s emerged as the first class of drugs in the early 1900s,<ref name="rzepa">{{cite web |title=Barbiturates |url=http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/barbiturate_text.htm |url-status=dead |archive-url=https://web.archive.org/web/20071107090620/http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/barbiturate_text.htm |archive-date=2007-11-07 |access-date=2007-10-31}}</ref> after which chemical substitution allowed derivative compounds. Although they were the best drug family at the time (with less toxicity and fewer side effects), they were dangerous in [[drug overdose|overdose]] and tended to cause physical and psychological dependence.<ref>{{cite journal |vauthors=Whitlock FA |date=June 1975 |title=Suicide in Brisbane, 1956 to 1973: the drug-death epidemic |journal=The Medical Journal of Australia |volume=1 |issue=24 |pages=737–743 |doi=10.5694/j.1326-5377.1975.tb111781.x |pmid=239307 |s2cid=28983030}}</ref><ref>{{cite journal |vauthors=Johns MW |year=1975 |title=Sleep and hypnotic drugs |journal=Drugs |volume=9 |issue=6 |pages=448–478 |doi=10.2165/00003495-197509060-00004 |pmid=238826 |s2cid=38775294}}</ref><ref>{{cite journal |vauthors=Jufe GS |date=July–August 2007 |title=[New hypnotics: perspectives from sleep physiology] |journal=Vertex |volume=18 |issue=74 |pages=294–299 |pmid=18265473}}</ref>

During the 1970s, [[quinazolinone]]s<ref>{{Cite journal |vauthors=Voegtle MM, Marzinzik AL |date=July 2004 |title=Synthetic Approaches Towards Quinazolines, Quinazolinones and Quinazolinediones on Solid Phase |journal=QSAR & Combinatorial Science |volume=23 |issue=6 |pages=440–459 |doi=10.1002/qsar.200420018 |issn=1611-020X}}</ref> and [[benzodiazepine]]s were introduced as safer alternatives to replace barbiturates; by the late 1970s, benzodiazepines emerged as the safer drug.<ref name="isbn0-19-517668-5" />

Benzodiazepines are not without their drawbacks; [[substance dependence]] is possible, and deaths from overdoses sometimes occur, especially in combination with [[alcohol (drug)|alcohol]] or other [[depressant]]s. Questions have been raised as to whether they disturb sleep architecture.<ref name="pmid15783240">{{cite journal |vauthors=Barbera J, Shapiro C |year=2005 |title=Benefit-risk assessment of zaleplon in the treatment of insomnia |journal=Drug Safety |volume=28 |issue=4 |pages=301–318 |doi=10.2165/00002018-200528040-00003 |pmid=15783240 |s2cid=24222535}}</ref>

[[Nonbenzodiazepine]]s are the most recent development (1990s–present). Although it is clear that they are less toxic than barbiturates, their predecessors, comparative efficacy over benzodiazepines has not been established. Such efficacy is hard to determine without [[longitudinal studies]]. However, some psychiatrists recommend these drugs, citing research suggesting they are equally potent with less potential for abuse.<ref name="pmid9640488a" />

Other sleep remedies that may be considered "sedative–hypnotics" exist; psychiatrists will sometimes prescribe medicines [[off-label]] if they have sedating effects. Examples of these include [[mirtazapine]] (an antidepressant), [[clonidine]] (an [[antihypertensive]] medication), [[quetiapine]] (an antipsychotic), and [[over-the-counter]] allergy and [[antiemetic]] medications [[doxylamine]] and [[diphenhydramine]]. Off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe (as in patients with a history of [[substance use disorder]]s).{{Citation needed|date=March 2025}}

==Effectiveness==
A major [[systematic review]] and [[network meta-analysis]] of medications for the treatment of insomnia was published in 2022.<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 | display-authors = 6 | 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 | journal = Lancet | volume = 400 | issue = 10347 | pages = 170–184 | date = July 2022 | pmid = 35843245 | doi = 10.1016/S0140-6736(22)00878-9 | s2cid = 250536370 | doi-access = free | hdl = 11380/1288245 | hdl-access = free }}</ref> It found a wide range of [[effect size]]s ([[standardized mean difference]] (SMD)) in terms of efficacy for insomnia.<ref name="pmid35843245" /> The assessed medications included [[benzodiazepine]]s (e.g., [[temazepam]], [[triazolam]], many others) (SMDs 0.58 to 0.83), [[Z-drug]]s ([[eszopiclone]], [[zaleplon]], [[zolpidem]], [[zopiclone]]) (SMDs 0.03 to 0.63), sedative [[antidepressant]]s and [[antihistamine]]s ([[doxepin]], [[doxylamine]], [[trazodone]], [[trimipramine]]) (SMDs 0.30 to 0.55), the [[antipsychotic]] [[quetiapine]] (SMD 0.07), [[orexin receptor antagonist]]s ([[daridorexant]], [[lemborexant]], [[seltorexant]], [[suvorexant]]) (SMDs 0.23 to 0.44), and [[melatonin receptor agonist]]s ([[melatonin (medication)|melatonin]], [[ramelteon]]) (SMDs 0.00 to 0.13).<ref name="pmid35843245" /> The [[certainty of evidence]] varied and ranged from high to very low depending on the medication.<ref name="pmid35843245" /> Certain medications often used as hypnotics, including the antihistamines [[diphenhydramine]], [[hydroxyzine]], and [[promethazine]] and the antidepressants [[amitriptyline]] and [[mirtazapine]], were not included in analyses due to insufficient data.<ref name="pmid35843245" />

==Risks==
The use of sedative medications in older people generally should be avoided. These medications are associated with poorer health outcomes, including [[cognitive decline]], and bone fractures.<ref>{{Cite journal |last1=Xu |first1=Chong |last2=Leung |first2=Janice Ching Nam |last3=Shi |first3=Jiaying |last4=Lum |first4=Dawn Hei |last5=Lai |first5=Francisco Tsz Tsun |date=February 2024 |title=Sedative-hypnotics and osteoporotic fractures: A systematic review of observational studies with over six million individuals |url=https://linkinghub.elsevier.com/retrieve/pii/S1087079223001223 |journal=Sleep Medicine Reviews |language=en |volume=73 |pages=101866 |doi=10.1016/j.smrv.2023.101866|pmid=37926010 }}</ref>

Therefore, sedatives and hypnotics should be avoided in people with dementia, according to the clinical guidelines known as the [[Medication appropriateness tool for co‐morbid health conditions in dementia (MATCH-D) criteria|Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D)]].<ref>Citation error. See the inline comment on how to fix it. {{verify source |date=September 2019 |reason=This ref was deleted Special:Diff/899881486 by a bug in VisualEditor and later identified by a bot. The original cite can be found around Special:Permalink/899881257 (or in a rev close to it) in either cite #24 or cite #23 - find and verify the cite and replace this template with it (1). [[User:GreenC bot/Job 18]]}}</ref> The use of these medications can further impede cognitive function for people with dementia, who are also more sensitive to side effects of medications.{{Citation needed|date=March 2025}}

== See also ==
* [[Sleep induction#Alcohol|Sleep induction § Alcohol]]

== Notes ==
<references group="note" />

== References ==
{{Reflist||colwidth=30em}}

== Further reading ==
{{refbegin|30em}}
* {{cite book | chapter-url=http://www.acnp.org/g4/GN401000173/CH169.html | vauthors = Harrison N, Mendelson WB, de Wit H |chapter = Barbiturates | veditors = Bloom FE, Kupfer DJ | title = Psychopharmacology | edition = The Fourth Generation of Progress |year=2000 | location = New York | publisher = Raven Press }} discusses Barbs vs. benzos
* {{cite journal | vauthors = Buysse DJ | title = Insomnia | journal = JAMA | volume = 309 | issue = 7 | pages = 706–716 | date = February 2013 | pmid = 23423416 | pmc = 3632369 | doi = 10.1001/jama.2013.193 }}
* {{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 }}
* {{cite journal | vauthors = Roehrs T, Roth T | title = Insomnia pharmacotherapy | journal = Neurotherapeutics | volume = 9 | issue = 4 | pages = 728–738 | date = October 2012 | pmid = 22976558 | pmc = 3480571 | doi = 10.1007/s13311-012-0148-3 }}
* {{cite journal | vauthors = Passos GS, Poyares DL, Santana MG, Tufik S, Mello MT | title = Is exercise an alternative treatment for chronic insomnia? | journal = Clinics | volume = 67 | issue = 6 | pages = 653–660 | date = 2012 | pmid = 22760906 | pmc = 3370319 | doi = 10.6061/clinics/2012(06)17 }}
* {{cite journal | vauthors = Becker DE | title = Pharmacodynamic considerations for moderate and deep sedation | journal = Anesthesia Progress | volume = 59 | issue = 1 | pages = 28–42 | date = Spring 2012 | pmid = 22428972 | pmc = 3309299 | doi = 10.2344/0003-3006-59.1.28 }}
* {{cite journal | vauthors = Godard M, Barrou Z, Verny M | title = [Geriatric approach of sleep disorders in the elderly] | journal = Psychologie & Neuropsychiatrie du Vieillissement | volume = 8 | issue = 4 | pages = 235–241 | date = December 2010 | pmid = 21147662 | pmc = <!--none--> | doi = 10.1684/pnv.2010.0232 }}
* {{cite journal | vauthors = Scammell TE, Winrow CJ | title = Orexin receptors: pharmacology and therapeutic opportunities | journal = Annual Review of Pharmacology and Toxicology | volume = 51 | pages = 243–266 | date = 2011 | pmid = 21034217 | pmc = 3058259 | doi = 10.1146/annurev-pharmtox-010510-100528 }}
* {{cite journal | vauthors = Sukys-Claudino L, Moraes WA, Tufik S, Poyares D | title = [The newer sedative-hypnotics] | journal = Revista Brasileira de Psiquiatria | volume = 32 | issue = 3 | pages = 288–293 | date = September 2010 | pmid = 20945020 | doi = 10.1590/S1516-44462010000300014 | doi-access = free }}
* {{cite journal | vauthors = Uzun S, Kozumplik O, Jakovljević M, Sedić B | title = Side effects of treatment with benzodiazepines | journal = Psychiatria Danubina | volume = 22 | issue = 1 | pages = 90–93 | date = March 2010 | pmid = 20305598 | url = http://hrcak.srce.hr/48626 }}
* {{cite journal | vauthors = Pigeon WR | title = Diagnosis, prevalence, pathways, consequences & treatment of insomnia | journal = The Indian Journal of Medical Research | volume = 131 | pages = 321–332 | date = February 2010 | pmid = 20308757 | pmc = 4324320 }}
* {{cite journal | vauthors = Hoque R, Chesson AL | title = Zolpidem-induced sleepwalking, sleep related eating disorder, and sleep-driving: fluorine-18-flourodeoxyglucose positron emission tomography analysis, and a literature review of other unexpected clinical effects of zolpidem | journal = Journal of Clinical Sleep Medicine | volume = 5 | issue = 5 | pages = 471–476 | date = October 2009 | pmid = 19961034 | pmc = 2762721 | doi = 10.5664/jcsm.27605 }}
{{refend}}

== External links ==
{{Wiktionary}}
* [http://www.circadin.com/treatments/sleeping-pills/ Sleeping pills overview]

{{Hypnotics and sedatives}}
{{Major drug groups}}
{{Insomnia pharmacotherapies}}
{{Chemical classes of psychoactive drugs}}
{{Authority control}}

{{DEFAULTSORT:Hypnotic}}

[[Category:Hypnotics| ]]
[[Category:Psychoactive drugs]]
[[Category:Treatment of sleep disorders]]