Hypnotic

Last updated
Zolpidem tartrate, a common but potent sedative-hypnotic drug. Used for severe insomnia. Stilnoct2.JPG
Zolpidem tartrate, a common but potent sedative–hypnotic drug. Used for severe insomnia.

Hypnotic (from Greek Hypnos, sleep [1] ), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep [2] (or surgical anesthesia [note 1] ) and to treat insomnia (sleeplessness).

Contents

This group of drugs is related to sedatives . Whereas the term sedative describes drugs that serve to calm or 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. [3]

Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries. [4] 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 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. [5]

Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines, while 10.8% are taking benzodiazepines, as of 2010, in the USA. [6] Early classes of drugs, such as barbiturates, 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 terrors or sleepwalking. [7] Elderly people are more sensitive to potential side effects of daytime fatigue and cognitive impairments, and a meta-analysis found that the risks generally outweigh any marginal benefits of hypnotics in the elderly. [8] A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs can have adverse effects, such as dependence and accidents, and that optimal treatment uses the lowest effective dose for the shortest therapeutic time period, with gradual discontinuation in order to improve health without worsening of sleep. [9]

Falling outside the above-mentioned categories, the neurohormone melatonin and its analogues (such as ramelteon) serve a hypnotic function. [10]

History

Le Vieux Seducteur by Charles Motte [fr]. (A corrupt old man tries to seduce a woman by urging her to take a hypnotic draught in her drink) A corrupt old man tries to seduce a woman by urging Wellcome L0034228.jpg
Le Vieux Séducteur by 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 and Ohloralamid or Chloralimid. [11]

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. [12] Barbiturates emerged as the first class of drugs in the early 1900s, [13] 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. [14] [15] [16]

During the 1970s, quinazolinones [17] and benzodiazepines were introduced as safer alternatives to replace barbiturates; by the late 1970s, benzodiazepines emerged as the safer drug. [12]

Benzodiazepines are not without their drawbacks; substance dependence is possible, and deaths from overdoses sometimes occur, especially in combination with alcohol and/or other depressants. Questions have been raised as to whether they disturb sleep architecture. [18]

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 have 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. [19]

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 older antihypertensive drug), quetiapine (an antipsychotic), and the 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 abuse).

Types

Barbiturates

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, hypnotics, and anticonvulsalgesic 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 GABAA receptors. [20]

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

Quinazolinones

Quinazolinones are also a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core. Their use has also been proposed in the treatment of cancer. [21]

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

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 the sleep time, and, in general, reducing wakefulness. [22] [23] 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). [24] [25] [26]

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. [27] [28] The list of benzodiazepines approved for the treatment of insomnia is fairly 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. [23] Longer-acting benzodiazepines such as nitrazepam and diazepam have residual effects that may persist into the next day and are, in general, not recommended. [22]

It is not clear as to whether the new nonbenzodiazepine hypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar. [22] [28] 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. [28] Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia. [23] 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. [22]

Older adults should not use benzodiazepines to treat insomnia—unless other treatments have failed to be effective. [29] 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. [4] [29]

Their mechanism of action is primarily at GABAA receptors. [30]

Nonbenzodiazepines

Nonbenzodiazepines are a class of psychoactive drugs that are very "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 entirely different chemical structures, and therefore are unrelated to benzodiazepines on a molecular level. [19] [31]

Examples include zopiclone (Imovane, Zimovane), eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Stilnox, Stilnoct). Since the generic names of all drugs of this type start with Z, they are often referred to as Z-drugs. [32]

Research on nonbenzodiazepines is new and conflicting. A review by a team of researchers suggests the use of these drugs for people that have trouble falling asleep (but not staying asleep), [note 2] as next-day impairments were minimal. [33] 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 ] A different team was more skeptical, finding little benefit over benzodiazepines. [34]

Others

Melatonin

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. [35] Ramelteon and tasimelteon are synthetic analogues of melatonin which are also used for sleep-related indications.

Antihistamines

In common use, the term antihistamine refers only to compounds that inhibit action at the H1 receptor (and not H2, etc.).

Clinically, H1 antagonists are used to treat certain allergies. Sedation is a common side-effect, and some H1 antagonists, such as diphenhydramine (Benadryl) and doxylamine, are also used to treat insomnia.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first ones.[ medical citation needed ] This results in their primarily affecting peripheral histamine receptors, and therefore having a much lower sedative effect. High doses can still induce the central nervous system effect of drowsiness.

Antidepressants

Some antidepressants have sedating effects.

Examples include:

Serotonin antagonists and reuptake inhibitors
Tricyclic antidepressants
Tetracyclic antidepressants

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 antipsychotics as the risks frequently outweigh the benefits. [43] [44] 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, [45] [46] [47] [48] 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. [49] Examples of antipsychotics with sedation as a side effect that are occasionally used for insomnia: [50]

First-generation
Second-generation

Miscellaneous drugs

Alpha-adrenergic agonist
Cannabinoids
Orexin receptor antagonist
Gabapentinoids

Effectiveness

A major systematic review and network meta-analysis of medications for the treatment of insomnia was published in 2022. [51] It found a wide range of effect sizes (standardized mean difference (SMD)) in terms of efficacy for insomnia. [51] 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). [51] The certainty of evidence varied and ranged from high to very low depending on the medication. [51] 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. [51]

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. [52]

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). [53] The use of these medications can further impede cognitive function for people with dementia, who are also more sensitive to side effects of medications.


See also

Notes

  1. ↑ When used in anesthesia to produce and maintain unconsciousness, "sleep" is metaphorical as there are no regular sleep stages or cyclical natural states; patients rarely recover from anesthesia feeling refreshed and with renewed energy. The word is also used in art.
  2. ↑ 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 not clear.

Related Research Articles

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

Benzodiazepines, colloquially known as "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, which followed with the development of diazepam (Valium) three years later, 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">Insomnia</span> Disorder causing trouble with sleeping

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 accidents of all kinds 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 distinct possibilities: insomnia disorder (ID) or insomnia symptoms, and many abstracts of randomized controlled trials and systematic reviews often underreport on which of these two possibilities the word refers to.

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

Temazepam, sold under the brand name Restoril among others, 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. Prescriptions for hypnotics such as temazepam have seen a dramatic decrease since 2010, while anxiolytics such as alprazolam, clonazepam, and lorazepam 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.

<span class="mw-page-title-main">Sedative</span> Drug that reduces excitement without inducing sleep

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 after 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, specifically a cyclopyrrolone, 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 inducing sedation but not with the anti-anxiety properties of the benzodiazepines.

<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 benzodiazepine hypnotic medications 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 used to treat insomnia

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 and approved for medical use in the United States in 1999.

<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, depressant, sedative, hypnotic, anxiolytic 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 the 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">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">SX-3228</span> Chemical compound

SX-3228 is a sedative and hypnotic drug used in scientific research. It has similar effects to sedative-hypnotic benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine hypnotic.

<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">Lemborexant</span> Chemical compound

Lemborexant, sold under the brand name Dayvigo, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. The medication is taken by mouth.

<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.

<span class="mw-page-title-main">Somnifacient</span> Class of medications that induce sleep

Somnifacient, 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.

References

  1. ↑ "Definition of HYPNOTIC". www.merriam-webster.com. Retrieved 2021-09-27.
  2. ↑ "Dorlands Medical Dictionary:hypnotic". Mercksource.com. Archived from the original on 2008-12-11.
  3. ↑ Brunton LL, Parker K, Lazo KL, Buxton I, Blumenthal D (2006). "17: Hypnotics and Sedatives". Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). The McGraw-Hill Companies, Inc. ISBN   978-0-07-146804-6 . Retrieved 2014-02-06.
  4. 1 2 National Prescribing Service (2 February 2010). "NPS News 67: Addressing hypnotic medicines use in primary care". Archived from the original on 22 February 2011. Retrieved 19 March 2010.
  5. ↑ Mendels J (September 1991). "Criteria for selection of appropriate benzodiazepine hypnotic therapy". The Journal of Clinical Psychiatry. 52. 52 (Suppl): 42–46. PMID   1680126.
  6. ↑ Kaufmann CN, Spira AP, Alexander GC, Rutkow L, Mojtabai R (June 2016). "Trends in prescribing of sedative-hypnotic medications in the USA: 1993-2010". Pharmacoepidemiology and Drug Safety. 25 (6): 637–645. doi:10.1002/pds.3951. PMC   4889508 . PMID   26711081.
  7. ↑ Gelder M, Mayou R, Geddes J (2005). Psychiatry (3rd ed.). New York: Oxford. p. 238.
  8. ↑ Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE (November 2005). "Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits". BMJ. 331 (7526): 1169. doi:10.1136/bmj.38623.768588.47. PMC   1285093 . PMID   16284208.
  9. ↑ "What's wrong with prescribing hypnotics?". Drug and Therapeutics Bulletin. 42 (12): 89–93. December 2004. doi:10.1136/dtb.2004.421289. PMID   15587763. S2CID   40188442.
  10. ↑ Zhdanova IV (February 2005). "Melatonin as a hypnotic: pro". Sleep Medicine Reviews. 9 (1): 51–65. doi:10.1016/j.smrv.2004.04.003. PMID   15649738.
  11. ↑ Pacific Record of Medicine and Surgery - Volume 5 - Page 36 1890
  12. 1 2 Shorter E (2005). "Benzodiazepines". A Historical Dictionary of Psychiatry. Oxford University Press. pp. 41–2. ISBN   978-0-19-517668-1 . Retrieved 2014-02-06.
  13. ↑ "Barbiturates". Archived from the original on 2007-11-07. Retrieved 2007-10-31.
  14. ↑ Whitlock FA (June 1975). "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic". The Medical Journal of Australia. 1 (24): 737–743. doi:10.5694/j.1326-5377.1975.tb111781.x. PMID   239307. S2CID   28983030.
  15. ↑ Johns MW (1975). "Sleep and hypnotic drugs". Drugs. 9 (6): 448–478. doi:10.2165/00003495-197509060-00004. PMID   238826. S2CID   38775294.
  16. ↑ Jufe GS (July–August 2007). "[New hypnotics: perspectives from sleep physiology]". Vertex. 18 (74): 294–299. PMID   18265473.
  17. ↑ Voegtle MM, Marzinzik AL (July 2004). "Synthetic Approaches Towards Quinazolines, Quinazolinones and Quinazolinediones on Solid Phase". QSAR & Combinatorial Science. 23 (6): 440–459. doi:10.1002/qsar.200420018. ISSN   1611-020X.
  18. ↑ Barbera J, Shapiro C (2005). "Benefit-risk assessment of zaleplon in the treatment of insomnia". Drug Safety. 28 (4): 301–318. doi:10.2165/00002018-200528040-00003. PMID   15783240. S2CID   24222535.
  19. 1 2 Wagner J, Wagner ML, Hening WA (June 1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". The Annals of Pharmacotherapy. 32 (6): 680–691. doi:10.1345/aph.17111. PMID   9640488. S2CID   34250754.
  20. ↑ Löscher W, Rogawski MA (December 2012). "How theories evolved concerning the mechanism of action of barbiturates". Epilepsia. 53 (Suppl 8): 12–25. doi: 10.1111/epi.12025 . PMID   23205959. S2CID   4675696.
  21. ↑ Chen K, Wang K, Kirichian AM, Al Aowad AF, Iyer LK, Adelstein SJ, Kassis AI (December 2006). "In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and therapy". Molecular Cancer Therapeutics. 5 (12): 3001–3013. doi: 10.1158/1535-7163.MCT-06-0465 . PMID   17172404.
  22. 1 2 3 4 "Technology Appraisal Guidance 77. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia" (PDF). National Institute for Clinical Excellence. April 2004. Archived from the original (PDF) on 2008-12-03. Retrieved 2009-07-26.
  23. 1 2 3 Ramakrishnan K, Scheid DC (August 2007). "Treatment options for insomnia". American Family Physician. 76 (4): 517–526. PMID   17853625.
  24. ↑ Ashton H (May 2005). "The diagnosis and management of benzodiazepine dependence". Current Opinion in Psychiatry. 18 (3): 249–255. doi:10.1097/01.yco.0000165594.60434.84. PMID   16639148. S2CID   1709063.
  25. ↑ Morin CM, Bélanger L, Bastien C, Vallières A (January 2005). "Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse". Behaviour Research and Therapy. 43 (1): 1–14. doi:10.1016/j.brat.2003.12.002. PMID   15531349.
  26. ↑ Poyares D, Guilleminault C, Ohayon MM, Tufik S (2004-06-01). "Chronic benzodiazepine usage and withdrawal in insomnia patients". Journal of Psychiatric Research. 38 (3): 327–334. doi:10.1016/j.jpsychires.2003.10.003. PMID   15003439.
  27. ↑ Maiuro RD (13 December 2009). Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research. Springer Publishing Company. pp. 128–30. ISBN   978-0-8261-1094-7.
  28. 1 2 3 Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, et al. (June 2005). "Manifestations and management of chronic insomnia in adults". Evidence Report/Technology Assessment (125). Agency for Healthcare Research and Quality: 1–10. doi:10.1037/e439752005-001. PMC   4781279 . PMID   15989374.
  29. 1 2 American Geriatrics Society. "Five Things Physicians and Patients Should Question". Choosing Wisely: an initiative of the ABIM Foundation . American Geriatrics Society. Retrieved August 1, 2013., which cites
  30. ↑ Olsen RW, Betz H (2006). "GABA and glycine". In Siegel GJ, Albers RW, Brady S, Price DD (eds.). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (7th ed.). Elsevier. pp. 291–302. ISBN   978-0-12-088397-4.
  31. ↑ Siriwardena AN, Qureshi Z, Gibson S, Collier S, Latham M (December 2006). "GPs' attitudes to benzodiazepine and 'Z-drug' prescribing: a barrier to implementation of evidence and guidance on hypnotics". The British Journal of General Practice. 56 (533): 964–967. PMC   1934058 . PMID   17132386.
  32. ↑ 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.
  33. ↑ Benca RM (March 2005). "Diagnosis and treatment of chronic insomnia: a review". Psychiatric Services. 56 (3): 332–343. doi:10.1176/appi.ps.56.3.332. PMID   15746509. 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 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.
  34. ↑ Wagner J, Wagner ML, Hening WA (June 1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". The Annals of Pharmacotherapy. 32 (6): 680–691. doi:10.1345/aph.17111. PMID   9640488. S2CID   34250754. 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.
  35. ↑ Arendt J, Skene DJ (February 2005). "Melatonin as a chronobiotic". Sleep Medicine Reviews. 9 (1): 25–39. doi:10.1016/j.smrv.2004.05.002. PMID   15649736.
  36. ↑ Haria M, Fitton A, McTavish D (April 1994). "Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders". Drugs & Aging. 4 (4): 331–355. doi:10.2165/00002512-199404040-00006. PMID   8019056. S2CID   265772823.
  37. ↑ "Levate (amitriptyline), dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 1 December 2013.
  38. ↑ Hajak G, Rodenbeck A, Voderholzer U, Riemann D, Cohrs S, Hohagen F, et al. (June 2001). "Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study". The Journal of Clinical Psychiatry. 62 (6): 453–463. doi:10.4088/JCP.v62n0609. PMID   11465523.
  39. ↑ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN   978-0-85711-084-8.[ page needed ]
  40. ↑ Wakeling A (April 1983). "Efficacy and side effects of mianserin, a tetracyclic antidepressant". Postgraduate Medical Journal. 59 (690): 229–231. doi:10.1136/pgmj.59.690.229. PMC   2417496 . PMID   6346303.
  41. ↑ Hartmann PM (January 1999). "Mirtazapine: a newer antidepressant". American Family Physician. 59 (1): 159–161. PMID   9917581.
  42. ↑ Jindal RD (2009). "Insomnia in patients with depression: some pathophysiological and treatment considerations". CNS Drugs. 23 (4): 309–329. doi:10.2165/00023210-200923040-00004. PMID   19374460. S2CID   22052011.
  43. ↑ Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ (2011). Off-Label Use of Atypical Antipsychotics: An Update. Comparative Effectiveness Reviews, No. 43. Rockville: Agency for Healthcare Research and Quality. PMID   22973576.
  44. ↑ Coe HV, Hong IS (May 2012). "Safety of low doses of quetiapine when used for insomnia". The Annals of Pharmacotherapy. 46 (5): 718–722. doi:10.1345/aph.1Q697. PMID   22510671. S2CID   9888209.
  45. ↑ Højlund M (2022-09-12). Low-dose Quetiapine: Utilization and Cardiometabolic Risk (Ph.D. thesis). University of Southern Denmark. doi:10.21996/mr3m-1783.
  46. ↑ Højlund M, Andersen K, Ernst MT, Correll CU, Hallas J (October 2022). "Use of low-dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator-controlled cohort study". World Psychiatry. 21 (3): 444–451. doi:10.1002/wps.21010. PMC   9453914 . PMID   36073694.
  47. ↑ Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, et al. (January 2020). "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". The Lancet. Psychiatry. 7 (1): 64–77. doi:10.1016/s2215-0366(19)30416-x. PMC   7029416 . PMID   31860457.
  48. ↑ Yoshida K, Takeuchi H (March 2021). "Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia". Behavioural Brain Research. 402: 113098. doi: 10.1016/j.bbr.2020.113098 . PMID   33417992. S2CID   230507941.
  49. ↑ De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, et al. (July 2022). "Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis". Lancet. 400 (10347): 170–184. doi: 10.1016/S0140-6736(22)00878-9 . hdl: 11380/1288245 . PMID   35843245. S2CID   250536370.
  50. ↑ Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID   23810019. S2CID   32085212.
  51. 1 2 3 4 5 De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, et al. (July 2022). "Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis". Lancet. 400 (10347): 170–184. doi: 10.1016/S0140-6736(22)00878-9 . hdl: 11380/1288245 . PMID   35843245. S2CID   250536370.
  52. ↑ Xu, Chong; Leung, Janice Ching Nam; Shi, Jiaying; Lum, Dawn Hei; Lai, Francisco Tsz Tsun (February 2024). "Sedative-hypnotics and osteoporotic fractures: A systematic review of observational studies with over six million individuals". Sleep Medicine Reviews. 73: 101866. doi:10.1016/j.smrv.2023.101866. PMID   37926010.
  53. ↑ Citation error. See inline comment how to fix. [ verification needed ]

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.