Somnifacient

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Etizolam is a benzodiazepine somnifacient for treating insomnia. Etizolam.jpg
Etizolam is a benzodiazepine somnifacient for treating insomnia.

Somnifacient (from Latin somnus, sleep [1] ), also known as sedatives or sleeping pills, is a class of medications that induces sleep. It is mainly used for treatment of insomnia. Examples of somnifacients include benzodiazepines, barbiturates and antihistamines.

Contents

Around 2-6% of adults with insomnia use somnifacients to aid sleep. [2] However, somnifacients only benefit transient or short-term insomnia but not chronic insomnia. [3] It is because somnifacients lack supportive evidence for sleep aids in chronic insomnia, and chronic use of somnifacients leads to many adverse effects. [4] [5] When somnifacient is used, it should be combined with Cognitive behavioural therapy for insomnia (CBT-I) and healthy sleeping habits but not solely used due to potential severe adverse effects. [6] [7]

Somnifacients are mainly in oral formulations, including tablets, capsules, solution and suspension, with an onset time within an hour. [8] One or two doses of somnifacients should be given for transient insomnia, while doses indicated for a week should be given for short-term insomnia. [9]

Types of somnifacients

Benzodiazepine Receptor Agonist

Gamma-aminobutyric acid is an inhibitory neurotransmitter for reducing excitability. Gamma-Aminobuttersaure - gamma-aminobutyric acid.svg
Gamma-aminobutyric acid is an inhibitory neurotransmitter for reducing excitability.

This class includes benzodiazepines and nonbenzodiazepines that have similar mechanisms of action but different chemical structures. They both act on and enhance the actions of gamma-aminobutyric acid (GABA)-A receptors, leading to an inhibitory effect on the brain and thus inducement of sleep. [10] [11]

Benzodiazepine

Benzodiazepines are somnifacients for the treatment of short-term insomnia. This class of drugs is characterized by the fusion of a diazepine ring and a benzene ring in the chemical structure. Examples of benzodiazepines are diazepam, nitrazepam, triazolam and chlordiazepoxide. Long-acting benzodiazepines, such as diazepam and chlordiazepoxide, are not recommended due to their residual effects that may precipitate the next day. [12]

Withdrawal syndrome is a common drawback of benzodiazepines because of the development of a physical dependence on them after abrupt withdrawal. It is characterized by sleep disturbance, tremors, increased anxiety and tension, headache, muscular stiffness and pain, which may last 10–14 days. [13] To avoid the problem, withdrawal of benzodiazepines should be carried out at a slow reduction rate, which is determined by the initial dose, duration of use and patient tolerance, but not abruptly. [3] Three basic approaches to the taper are using the same medication for tapering, adding adjunctive medication for alleviating withdrawal symptoms, and switching to a longer-acting equivalent. [14] One of the recommended benzodiazepine taper is to reduce the dose by 50% in the first 4 weeks, maintain the dose for 1–2 months, and then reduce the dose by 25% every 2 weeks. [15] Other common side effects of benzodiazepines are drowsiness, dizziness, somnolence and increased risk of ataxia.

Benzodiazepines should not be taken with other central nervous system depressants, namely anticonvulsants, other types of somnifacients, antihistamines and alcohol, because it may potentially increase the toxic effects of benzodiazepines. [16] Besides, the US Food and Drug Administration (FDA) added a boxed warning for benzodiazepines regarding the concomitant use of opioid drugs because it may increase the risk of coma, respiratory depression, general anesthesia, and death. [17] The elderly should avoid the use of benzodiazepines due to the increased risk of cognitive impairment, falls and fractures. [18] Benzodiazepines are also contraindicated in pregnancy and breast-feeding women since they may cause floppy infant syndrome in infants, characterized by hypotonia and CNS depression. [16]

Nonbenzodiazepine

Nonbenzodiazepines, also known as benzodiazepine-like drugs or Z-drugs, are somnifacients indicated for short-term insomnia. Examples include zolpidem (Ambien, Stilnoct, Stilnox), zopiclone (Imovane, Zimovane), and zaleplon (Sonata).

Zolpidem (immediate release) is considered the first choice for patients with either sleep maintenance or sleep onset complaints. In cases where patients experience waking up at midnight or too early in the morning, zolpidem (extended release) or eszopiclone may be considered due to their longer actions. Zaleplon with the shortest half-life of the nonbenzodiazepines is suitable for patients who experience residual sedating effects in the morning. [5] However, the exact medication chosen depends on the patient's tolerance, varied efficacy in individuals and drug interactions.

Nonbenzodiazepines, theoretically, are associated with greater selectivity for several subtypes of GABA-A receptors than benzodiazepines, potentially leading to a narrower range of side effects and therapeutic outcomes. [5] However, research findings on the comparison between benzodiazepines and nonbenzodiazepines in terms of efficacy and adverse effects are conflicting. The US Agency for Healthcare Research and Quality indicates that the risk of harm from benzodiazepines is about twice as high as that from nonbenzodiazepines. [19] Another study points out that there is no significant difference between the two classes of drugs in terms of adverse effects. [20] Unlike benzodiazepines, nonbenzodiazepines appear to have little or no impact on sleep stages and do not lead to rapid-eye-movement (REM) sleep rebound. [21] However, as per a review by the National Institute for Health and Clinical Excellence (NICE), inadequate evidence supports the use of Z-drugs for treating insomnia. The review noted that clinical trials inappropriately compared short-acting nonbenzodiazepines with long-acting benzodiazepines, and there is a lack of studies that compare the effects of short-acting nonbenzodiazepines to those of short-acting benzodiazepines at equivalent doses. As a result of these findings, NICE recommended taking both the patient's preferences and the product price per dose into account when prescribing a somnifacient. [22]

Barbiturate is used as an anaesthetic medication during surgical operation. US Navy 030227-N-9228K-004 Hospital Corpsman Desmond Smith from Tupelo, Miss., assigned to the Medical Department aboard USS Abraham Lincoln (CVN 72), gives a patient a digital block shot as a local anesthetic in preparation fo.jpg
Barbiturate is used as an anaesthetic medication during surgical operation.

Like benzodiazepines, nonbenzodiazepines are contraindicated in the elderly and pregnant due to potential adverse effects. Although it is hypothesized that somnifacients may help treat depression caused by insomnia, data released by the Food and Drug Administration (FDA) shows that the use of nonbenzodiazepines including zolpidem, zaleplon and eszopiclone increased the risk of depression by over two times when compared to individuals taking placebo pills. [23] Therefore, patients who suffer from or are at risk of depression may not be suitable for taking nonbenzodiazepines. The dose of nonbenzodiazepines should be reduced in patients with renal dysfunction due to the hepatic metabolism of the drugs. [24]

Barbiturates

Barbiturates are a class of sedative drugs that potentiate the action of GABA on GABA-A receptors. [25] Their effects range from moderate sedation to total anesthesia according to the doses indicated. Due to the significant adverse effects (i.e. hallucination, agitation, confusion and hangover) and higher risk of overdose, barbiturates are now mostly replaced by benzodiazepine receptor agonists or other somnifacients in clinical practice for treating insomnia. [21] Barbiturates are commonly used in epilepsy, acute migraines, general anesthesia, and assisted suicide. [26] Examples of barbiturates are phenobarbital, primidone and amobarbital.

Antihistamine

Diphenhydramine (Benadryl) is commonly used for treating allergic rhinitis and urticaria. Benadryl tablets (4438315926).jpg
Diphenhydramine (Benadryl) is commonly used for treating allergic rhinitis and urticaria.

Antihistamines, also known as H1 antagonists, are a class of drugs which inhibit action at H1 receptors. They are clinically used to alleviate allergic reactions including allergic rhinitis, allergic conjunctivitis and urticaria mediated by histamine. [27] First generation antihistamines such as doxylamine and diphenhydramine are accompanied by sedation as the side effect, which can be utilized to treat insomnia. Some of the antihistamines, namely promethazine and doxylamine, are available for purchase over-the-counter (OTC) and can be bought by the public in some countries for the occasional relief of insomnia. [28] Low-dose doxepin is approved by the FDA for the treatment of insomnia. [5] 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. [29]

Common side effects of antihistamines include nausea, constipation and dry mouth. [27] Patients with severe urinary retention or untreated angle-closure glaucoma should avoid antihistamines. [5]

Melatonin/ Melatonin receptor agonist

Melatonin is an endogenous hormone synthesized in the pineal gland in the brain involved in promoting sleep. [30] It activates both melatonin receptors MT1 and MT2 to produce beneficial effects on sleep, therefore being used exogenously for mild insomnia. [31] A small improvement in sleep onset and total sleep time by using melatonin has been shown in recent systematic reviews. [32] Synthetic melatonin, also known as melatonin receptor agonist, is also used for sleeping disorders by mimicking the action of melatonin. Examples are tasimelteon and ramelteon.

Dual orexin receptor antagonist

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. [33] Daridorexant, lemborexant and suvorexant have been shown in studies to improve sleep onset and sleep quality. [34] [35]

Miscellaneous drugs

Antipsychotics [36]

Antidepressants [37]

Cannabinoids [38]

Miscellaneous drugs of somnifacients show sedative effects, but they are not first-line use for insomnia or they are prescribed off-label for insomnia. When prescribing these drugs for insomnia, extra care is needed due to unexpected outcomes and benefit-risk ratios compared to approved medications for insomnia. [39]

Precautions and contraindications

All somnifacients have shared risks of worsening depression, central nervous system depressant effects, abnormal thinking and behaviour changes. [5] It is not advisable to prescribe somnifacients for routine insomnia treatment, and they should only be used for short periods in patients who are severely distressed or with transient insomnia. [40] An important drawback of prolonged use is that it can result in rebound insomnia and withdrawal syndrome upon discontinuation. [40] The elderly especially those with dementia should avoid somnifacients due to potential further impairment of cognitive function according to the clinical guideline, Medication Appropriateness Tool for Comorbid Health Conditions in Dementia. [41] Most somnifacients possess Cytochrome P450 (CYP450) metabolism, a major drug metabolism pathway in the body, which may have potential drug interactions with other drugs affecting CYP450 activity, such as ketoconazole, clarithromycin and fluvoxamine. [5] Patients with polypharmacy require extra attention due to the their complex medication regimens.

Related Research Articles

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Hypnotic</span> Drug whose use induces sleep

Hypnotic, or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness).

<span class="mw-page-title-main">Insomnia</span> Inability to fall or stay asleep

Insomnia, also known as sleeplessness, is a sleep disorder where people have trouble sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, irritability, and a depressed mood. It may result in an increased risk of motor vehicle collisions, as well as problems focusing and learning. Insomnia can be short term, lasting for days or weeks, or long term, lasting more than a month. The concept of the word insomnia has two possibilities: insomnia disorder and insomnia symptoms, and many abstracts of randomized controlled trials and systematic reviews often underreport on which of these two possibilities the word insomnia refers to.

<span class="mw-page-title-main">Temazepam</span> Insomnia medication

Temazepam is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hypnotic effects begin in less than 30 minutes and can last for up to eight hours. Many studies, some going as far back as the early 1980s out of Australia and the United Kingdom, both of which have had serious temazepam abuse epidemics and related mortality, have all mostly corroborated each other and proven that the potential for abuse and physical dependence is very high, even in comparison to many other benzodiazepines. As a result, prescriptions for hypnotics such as temazepam have seen a dramatic decrease since 2010, while anxiolytics such as alprazolam (Xanax), clonazepam, and lorazepam (Ativan) have increased or remained stable. Temazepam and similar hypnotics, such as triazolam (Halcion) are generally reserved for severe and debilitating insomnia. They have largely been replaced by z-drugs and atypical antidepressants as first line treatment for insomnia.

A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity.

<span class="mw-page-title-main">Zolpidem</span> Hypnotic medication

Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do.

<span class="mw-page-title-main">Flurazepam</span> Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals was one of the first benzo hypnotics to be marketed.

<span class="mw-page-title-main">Eszopiclone</span> Hypnotic medication

Eszopiclone, sold under the brand name Lunesta among others, is a medication used in the treatment of insomnia. Evidence supports slight to moderate benefit up to six months. It is taken by mouth.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Zaleplon</span> Medication

Zaleplon, sold under the brand name Sonata among others, is a sedative and hypnotic which is used to treat insomnia. It is a nonbenzodiazepine or Z-drug of the pyrazolopyrimidine class. It was developed by King Pharmaceuticals.

<span class="mw-page-title-main">Nonbenzodiazepine</span> Class of psychoactive drugs

Nonbenzodiazepines, sometimes referred to colloquially as Z-drugs, are a class of psychoactive drugs that are benzodiazepine-like in uses, such as for treating insomnia and anxiety.

<span class="mw-page-title-main">Quazepam</span> Benzodiazipine

Quazepam, sold under brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.

<span class="mw-page-title-main">Estazolam</span> Tranquilizer

Estazolam, sold under the brand name Prosom among others, is a tranquilizer medication of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Estazolam is an intermediate-acting oral benzodiazepine. It is used for short-term treatment of insomnia.

<span class="mw-page-title-main">Lormetazepam</span> Benzodiazepine medication

Lormetazepam, sold under the brand name Noctamid among others, is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative and temazepam analogue. It possesses hypnotic, anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, however, the continued use seems to be associated with the avoidance of unpleasant withdrawal reaction rather than from the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, without the described dependence behavior.

<span class="mw-page-title-main">Barbiturate</span> Class of depressant drugs derived from barbituric acid

Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as well as overdose potential among other possible adverse effects. They have been used recreationally for their anti-anxiety and sedative effects, and are thus controlled in most countries due to the risks associated with such use.

<span class="mw-page-title-main">TIK-301</span> Chemical compound

TIK-301 (LY-156735) is an agonist for the melatonin receptors MT1 and MT2 that is under development for the treatment of insomnia and other sleep disorders. Its agonist action on MT1 and MT2 receptors in the suprachiasmatic nucleus in the brain enables its action as a chronobiotic. It is in the same class of melatonin receptor agonists as ramelteon and tasimelteon.

<span class="mw-page-title-main">Daridorexant</span> Medication used to treat insomnia

Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia. Daridorexant is taken by mouth.

References

  1. ↑ "Definition of SOMNIFACIENT". www.merriam-webster.com. Retrieved 13 March 2023.
  2. ↑ Ohayon, Maurice M. (2002). "Epidemiology of insomnia: what we know and what we still need to learn". Sleep Medicine Reviews. 6 (2): 97–111. doi:10.1053/smrv.2002.0186. PMID   12531146.
  3. 1 2 "MedicinesComplete — CONTENT > BNF > Hypnotics and anxiolytics". Medicinescomplete.com. Retrieved 13 March 2023.
  4. ↑ Kripke, Daniel F. (2013). Risks of Chronic Hypnotic Use. Landes Bioscience.
  5. 1 2 3 4 5 6 7 "Pharmacotherapy for insomnia in adults". www.uptodate.com. Retrieved 13 March 2023.
  6. ↑ Qaseem, Amir; Kansagara, Devan; Forciea, Mary Ann; Cooke, Molly; Denberg, Thomas D.; Clinical Guidelines Committee of the American College of Physicians (19 July 2016). "Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians". Annals of Internal Medicine. 165 (2): 125–133. doi: 10.7326/M15-2175 . ISSN   1539-3704. PMID   27136449. S2CID   207538494.
  7. ↑ Sateia, Michael J.; Buysse, Daniel J.; Krystal, Andrew D.; Neubauer, David N.; Heald, Jonathan L. (15 February 2017). "Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline". Journal of Clinical Sleep Medicine. 13 (2): 307–349. doi:10.5664/jcsm.6470. ISSN   1550-9397. PMC   5263087 . PMID   27998379.
  8. ↑ Donaldson, Mark; Gizzarelli, Gino; Chanpong, Brian (2007). "Oral sedation: a primer on anxiolysis for the adult patient". Anesthesia Progress. 54 (3): 118–128, quiz 129. doi:10.2344/0003-3006(2007)54[118:OSAPOA]2.0.CO;2. ISSN   0003-3006. PMC   1993866 . PMID   17900211.
  9. ↑ "MedicinesComplete — CONTENT > MARTINDALE > Insomnia (Anxiolytic Sedatives Hypnotics and Antipsychotics - Sleep disorders)". Medicinescomplete.com.
  10. ↑ Griffin, Charles E.; Kaye, Adam M.; Bueno, Franklin Rivera; Kaye, Alan D. (2013). "Benzodiazepine pharmacology and central nervous system-mediated effects". The Ochsner Journal. 13 (2): 214–223. ISSN   1524-5012. PMC   3684331 . PMID   23789008.
  11. ↑ Morin, Charles M.; Beaulieu-Bonneau, Simon; Cheung, Janet M.Y. (1 January 2019). "Treatment of Insomnia". Handbook of Sleep Disorders in Medical Conditions: 27–50. doi:10.1016/B978-0-12-813014-8.00002-0. ISBN   9780128130148. S2CID   87505809.
  12. ↑ "Overview | Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia | Guidance | NICE". www.nice.org.uk. 28 April 2004. Retrieved 13 March 2023.
  13. ↑ Pétursson, H. (1994). "The benzodiazepine withdrawal syndrome". Addiction. 89 (11): 1455–1459. doi:10.1111/j.1360-0443.1994.tb03743.x. ISSN   0965-2140. PMID   7841856.
  14. ↑ Ogbonna, Chinyere I.; Lembke, Anna (1 November 2017). "Tapering Patients Off of Benzodiazepines". American Family Physician. 96 (9): 606–608. PMID   29094883.
  15. ↑ "Effective Treatments for PTSD: Helping Patients Taper from Benzodiazepines" (PDF). National Center for PTSD.
  16. 1 2 "benzo.org.uk : Toxicity and Adverse Consequences of Benzodiazepine Use, Professor Ashton, 1995". www.benzo.org.uk. Retrieved 13 March 2023.
  17. ↑ "FDA adds Boxed Warning on risk of death with febuxostat". Reactions Weekly. 1742 (1): 1. 2019. doi:10.1007/s40278-019-58459-9. ISSN   0114-9954. S2CID   195088444.
  18. ↑ American Geriatrics Society 2012 Beers Criteria Update Expert Panel (2012). "American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults". Journal of the American Geriatrics Society. 60 (4): 616–631. doi:10.1111/j.1532-5415.2012.03923.x. ISSN   1532-5415. PMC   3571677 . PMID   22376048.
  19. ↑ Buscemi, Nina; Vandermeer, Ben; Friesen, Carol; Bialy, Liza; Tubman, Michelle; Ospina, Maria; Klassen, Terry P.; Witmans, Manisha (June 2005). Manifestations and Management of Chronic Insomnia in Adults. Agency for Healthcare Research and Quality (US).
  20. ↑ Wagner, J.; Wagner, M. L.; Hening, W. A. (1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". The Annals of Pharmacotherapy. 32 (6): 680–691. doi:10.1345/aph.17111. ISSN   1060-0280. PMID   9640488. S2CID   34250754.
  21. 1 2 Ramakrishnan, Kalyanakrishnan; Scheid, Dewey C. (15 August 2007). "Treatment Options for Insomnia". American Family Physician. 76 (4): 517–526. PMID   17853625.
  22. ↑ Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia (PDF). National Institute for Health and Care Excellence. April 2004. ISBN   1-84257-606-2. Archived from the original (PDF) on 3 December 2008. Retrieved 2 July 2023.
  23. ↑ Kripke, Daniel F. (21 August 2007). "Greater incidence of depression with hypnotic use than with placebo". BMC Psychiatry. 7: 42. doi:10.1186/1471-244X-7-42. ISSN   1471-244X. PMC   1994947 . PMID   17711589.
  24. ↑ Toner, Laura C.; Tsambiras, Belen M.; Catalano, Glenn; Catalano, Maria C.; Cooper, David S. (2000). "Central Nervous System Side Effects Associated with Zolpidem Treatment". Clinical Neuropharmacology. 23 (1): 54–58. doi:10.1097/00002826-200001000-00011. ISSN   0362-5664. PMID   10682233.
  25. ↑ Löscher, Wolfgang; Rogawski, Michael A. (2012). "How theories evolved concerning the mechanism of action of barbiturates". Epilepsia. 53 Suppl 8: 12–25. doi: 10.1111/epi.12025 . ISSN   1528-1167. PMID   23205959. S2CID   4675696.
  26. ↑ "Brochure of DIGNITAS". www.dignitas.ch. Retrieved 13 March 2023.
  27. 1 2 "MedicinesComplete — CONTENT > BNF > antihistamine". Medicinescomplete.com. Retrieved 13 March 2020.
  28. ↑ Culpepper, Larry; Wingertzahn, Mark A. (2015). "Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety". The Primary Care Companion for CNS Disorders. 17 (6). doi:10.4088/PCC.15r01798. ISSN   2155-7772. PMC   4805417 . PMID   27057416.
  29. ↑ Slater, J. W.; Zechnich, A. D.; Haxby, D. G. (1999). "Second-generation antihistamines: a comparative review". Drugs. 57 (1): 31–47. doi:10.2165/00003495-199957010-00004. ISSN   0012-6667. PMID   9951950. S2CID   46984477.
  30. ↑ "Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders". openresearch.surrey.ac.uk.
  31. ↑ Liu, Jiabei; Clough, Shannon J.; Hutchinson, Anthony J.; Adamah-Biassi, Ekue B.; Popovska-Gorevski, Marina; Dubocovich, Margarita L. (2016). "MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective". Annual Review of Pharmacology and Toxicology. 56: 361–383. doi:10.1146/annurev-pharmtox-010814-124742. ISSN   1545-4304. PMC   5091650 . PMID   26514204.
  32. ↑ Low, Tian Ling; Choo, Faith Nadine; Tan, Shian Ming (2020). "The efficacy of melatonin and melatonin agonists in insomnia - An umbrella review". Journal of Psychiatric Research. 121: 10–23. doi:10.1016/j.jpsychires.2019.10.022. ISSN   1879-1379. PMID   31715492. S2CID   207949129.
  33. ↑ Mieda, Michihiro; Tsujino, Natsuko; Sakurai, Takeshi (2013). "Differential roles of orexin receptors in the regulation of sleep/wakefulness". Frontiers in Endocrinology. 4: 57. doi: 10.3389/fendo.2013.00057 . ISSN   1664-2392. PMC   3656340 . PMID   23730297.
  34. ↑ Kuriyama, Akira; Tabata, Hiromitsu (2017). "Suvorexant for the treatment of primary insomnia: A systematic review and meta-analysis". Sleep Medicine Reviews. 35: 1–7. doi:10.1016/j.smrv.2016.09.004. ISSN   1532-2955. PMID   28365447.
  35. ↑ Mignot, Emmanuel; Mayleben, David; Fietze, Ingo; Leger, Damien; Zammit, Gary; Bassetti, Claudio L. A.; Pain, Scott; Kinter, Dalma Seboek; Roth, Thomas; investigators (2022). "Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials". The Lancet. Neurology. 21 (2): 125–139. doi:10.1016/S1474-4422(21)00436-1. ISSN   1474-4465. PMID   35065036. S2CID   246054876.
  36. ↑ Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R.; Geddes, John R.; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M. (14 September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". The Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. ISSN   0140-6736. PMID   23810019. S2CID   32085212.
  37. ↑ Everitt, Hazel; Baldwin, David S.; Stuart, Beth; Lipinska, Gosia; Mayers, Andrew; Malizia, Andrea L.; Manson, Christopher Cf; Wilson, Sue (14 May 2018). "Antidepressants for insomnia in adults". The Cochrane Database of Systematic Reviews. 2018 (5): CD010753. doi:10.1002/14651858.CD010753.pub2. ISSN   1469-493X. PMC   6494576 . PMID   29761479.
  38. ↑ Lavender, Isobel; McGregor, Iain S.; Suraev, Anastasia; Grunstein, Ronald R.; Hoyos, Camilla M. (2022). "Cannabinoids, Insomnia, and Other Sleep Disorders". Chest. 162 (2): 452–465. doi:10.1016/j.chest.2022.04.151. ISSN   1931-3543. PMID   35537535. S2CID   248584784.
  39. ↑ By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel (2019). "American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults". Journal of the American Geriatrics Society. 67 (4): 674–694. doi:10.1111/jgs.15767. ISSN   1532-5415. PMID   30693946. S2CID   59338182.
  40. 1 2 "MedicinesComplete — CONTENT > BNF > anxiolytics". Medicinescomplete.com. Retrieved 13 March 2023.
  41. ↑ Page, A. T.; Potter, K.; Clifford, R.; McLachlan, A. J.; Etherton-Beer, C. (2016). "Medication appropriateness tool for co-morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel". Internal Medicine Journal. 46 (10): 1189–1197. doi:10.1111/imj.13215. ISSN   1445-5994. PMC   5129475 . PMID   27527376.
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