hypnotic

{{Main|Barbiturate}}

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a broad spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, 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 and psychological. Barbiturates have now largely been replaced by benzodiazepines in routine medical practice – such as in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in 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 modulation of GABA_A receptors.{{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 }}

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

{{main|Quinazolinone}}

{{See also|Methaqualone}}

Quinazolinones 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.{{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 }}

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

{{main|Benzodiazepine#Insomnia}}

{{See also|List of benzodiazepines}}

Benzodiazepines 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.{{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 }}{{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 }} Like 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).{{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 }}{{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 }}{{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 }}

Other drawbacks of hypnotics, including benzodiazepines, are possible 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.{{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}} 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. Longer-acting benzodiazepines, such as nitrazepam and diazepam, have residual effects that may persist into the next day and are, in general, not recommended.

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. 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.{{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 }} Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia. 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.

Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed to be effective.{{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 }} 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.

Their mechanism of action is primarily at GABA_A receptors.{{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}}

{{Main|Nonbenzodiazepines}}

Nonbenzodiazepines (Z-drugs) are a class of psychoactive drugs 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.{{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}}{{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 }}

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.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.

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),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. as next-day impairments were minimal.{{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. }} 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 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.{{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 }}

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 diurnal mammals.{{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 }} It activates both melatonin receptors MT₁ and MT₂ to produce beneficial effects on sleep, therefore being used exogenously for mild insomnia.{{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}} A small improvement in sleep onset and total sleep time by using melatonin has been shown in recent systematic reviews.{{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}}

Synthetic analogues of melatonin, or melatonin receptor agonists, 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.{{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 = }}

{{Main|H1 antagonist}}

Antihistamines, also known as H₁ antagonists, are a class of drugs that inhibit action at H₁ 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.{{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}} Low-dose doxepin is approved by the FDA for the treatment of insomnia.{{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}} 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.{{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}}

In common use, the term antihistamine refers only to compounds that inhibit action at the H₁ receptor.{{Citation needed|date=March 2025}}

Clinically, H₁ antagonists are used to treat certain allergies. Sedation is a common side effect, and some H₁ antagonists, such as diphenhydramine and doxylamine, are also used to treat insomnia.{{Citation needed|date=March 2025}}

Dual orexin receptor antagonists are drugs that block the orexin receptors OX₁ and OX₂, hence reducing the wakeful effect of the orexin system and inducing sleep.{{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}} Orexin antagonists daridorexant, lemborexant, and suvorexant have been shown in studies to improve sleep onset and sleep quality.{{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}}{{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}}

Some antidepressants have sedating effects.

Examples include:

; Serotonin antagonist and reuptake inhibitors

• Trazodone{{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 }}

; Tricyclic antidepressants

• Amitriptyline{{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}}
• Doxepin{{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 }}
• Trimipramine

{{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}}

; Tetracyclic antidepressants

• Mianserin{{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 }}
• Mirtazapine{{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 }}{{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 }}

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 antipsychotics as the risks frequently outweigh the benefits.{{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}}{{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 }} 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,{{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}}{{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 }}{{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 }}{{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 }} 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.{{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 }} Examples of antipsychotics with sedation as a side effect that are occasionally used for insomnia:{{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 }}

; First-generation

• Chlorpromazine

; Second-generation

• Clozapine
• Olanzapine
• Quetiapine
• Risperidone
• Zotepine
• Ziprasidone

{{Unreferenced section|date=March 2025}}

; Alpha-adrenergic agonist

• Clonidine
• Guanfacine

; Cannabinoids

• Cannabidiol
• Tetrahydrocannabinol

; Gabapentinoids

• Gabapentin
• Pregabalin
• Phenibut

File:A corrupt old man tries to seduce a woman by urging Wellcome L0034228.jpg by {{Interlanguage link multi|Charles Motte|fr}}.
(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 urethan, acetal, methylal, sulfonal, paraldehyde, amylenhydrate, hypnon, chloralurethan, ohloralamid, or chloralimid.Pacific Record of Medicine and Surgery - Volume 5 - Page 36 1890

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.{{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}} Barbiturates emerged as the first class of drugs in the early 1900s,{{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}} 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 overdose and tended to cause physical and psychological dependence.{{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}}{{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}}{{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}}

During the 1970s, quinazolinones{{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}} and benzodiazepines were introduced as safer alternatives to replace barbiturates; by the late 1970s, benzodiazepines emerged as the safer drug.

Benzodiazepines are not without their drawbacks; substance dependence is possible, and deaths from overdoses sometimes occur, especially in combination with alcohol or other depressants. Questions have been raised as to whether they disturb sleep architecture.{{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}}

Nonbenzodiazepines 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.

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 disorders).{{Citation needed|date=March 2025}}

A major systematic review and network meta-analysis of medications for the treatment of insomnia was published in 2022.{{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 }} It found a wide range of effect sizes (standardized mean difference (SMD)) in terms of efficacy for insomnia. The assessed medications included benzodiazepines (e.g., temazepam, triazolam, many others) (SMDs 0.58 to 0.83), Z-drugs (eszopiclone, zaleplon, zolpidem, zopiclone) (SMDs 0.03 to 0.63), sedative antidepressants and antihistamines (doxepin, doxylamine, trazodone, trimipramine) (SMDs 0.30 to 0.55), the antipsychotic quetiapine (SMD 0.07), orexin receptor antagonists (daridorexant, lemborexant, seltorexant, suvorexant) (SMDs 0.23 to 0.44), and melatonin receptor agonists (melatonin, ramelteon) (SMDs 0.00 to 0.13). The certainty of evidence varied and ranged from high to very low depending on the medication. 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.

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.{{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 |url-access=subscription }}

Therefore, sedatives and hypnotics should be avoided in people with dementia, according to the clinical guidelines known as the Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D).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}} 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}}

• Sleep induction § Alcohol

{{Reflist||colwidth=30em}}

{{refbegin|30em}}

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{{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:Psychoactive drugs

Category:Treatment of sleep disorders