Wikipedia

Hypnotic

(Redirected fromSoporific)
This article is about the class of prescription medicines. For the state of mind, seeHypnosis.For other uses, seeHypnotic (disambiguation).
"Sleeping pills" redirects here. For the 2003 film, seeSleeping Pills (film).
See also:Sedative

Hypnotic(fromGreekHypnos,sleep[1]), orsoporificdrugs, commonly known assleeping pills,are a class of (and umbrella term for)psychoactive drugswhose primary function is toinduce sleep[2](or surgicalanesthesia[note 1]) and to treatinsomnia(sleeplessness).

refer to caption
Zolpidem tartrate,a common but potent sedative–hypnotic drug. Used for severe insomnia.

This group of drugs is related tosedatives.Whereas the term sedative describes drugs that serve to calm orrelieve 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 fromanxiolysistoloss of consciousness), they are often referred to collectively assedative–hypnoticdrugs.[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, bettersleep hygiene,the avoidance of caffeine andalcoholor other stimulating substances, or behavioral interventions such ascognitive 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 prescribednonbenzodiazepines,while 10.8% are takingbenzodiazepines,as of 2010, in the USA.[6]Early classes of drugs, such asbarbiturates,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 treatnight terrorsorsleepwalking.[7]Elderly people are more sensitive to potential side effects of daytime fatigue andcognitive impairments,and ameta-analysisfound that the risks generally outweigh any marginal benefits of hypnotics in the elderly.[8]A review of the literature regarding benzodiazepine hypnotics andZ-drugsconcluded that these drugs can have adverse effects, such asdependenceand 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 neurohormonemelatoninand its analogues (such asramelteon) serve a hypnotic function.[10]

History

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Le VieuxSéducteurbyCharles Motte[fr].
(A corrupt old man tries to seduce a woman by urging her to take a hypnotic draught in her drink)

Hypnoticawas a class of somniferous drugs and substances tested in medicine of the 1890s and later. These includeUrethan,Acetal,Methylal,Sulfonal,Paraldehyde,Amylenhydrate,Hypnon,ChloralurethanandOhloralamidorChloralimid.[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, whenchloral hydratewas first used as a soporific.[12]Barbituratesemerged 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 inoverdoseand tended to cause physical and psychological dependence.[14][15][16]

During the 1970s,quinazolinones[17]andbenzodiazepineswere 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 dependenceis possible, and deaths from overdoses sometimes occur, especially in combination withalcoholand/or otherdepressants.Questions have been raised as to whether they disturb sleep architecture.[18]

Nonbenzodiazepinesare 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 withoutlongitudinal 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 medicinesoff-labelif they have sedating effects. Examples of these includemirtazapine(an antidepressant),clonidine(an olderantihypertensive drug),quetiapine(an antipsychotic), and theover-the-counterallergy andantiemeticmedicationsdoxylamineanddiphenhydramine.Off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe (as in patients with a history ofsubstance abuse).

Types

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Main articles:Barbiturate,Quinazolinone,Benzodiazepine,andNonbenzodiazepine

Barbiturates

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Main article:Barbiturate

Barbiturates are drugs that act ascentral nervous systemdepressants,and can therefore produce a wide spectrum of effects, from mildsedationto totalanesthesia.They are also effective asanxiolytics,hypnotics, andanticonvulsalgesiceffects; however, these effects are somewhat weak, preventing barbiturates from being used insurgeryin the absence of other analgesics. They have dependence liability, bothphysicalandpsychological.Barbiturates have now largely been replaced bybenzodiazepinesin routine medical practice – such as in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous inoverdose.However, barbiturates are still used in general anesthesia, forepilepsy,and forassisted suicide.Barbiturates are derivatives ofbarbituric acid.

The principalmechanism of actionof barbiturates is believed to bepositive allosteric modulationofGABAAreceptors.[20]

Examples includeamobarbital,pentobarbital,phenobarbital,secobarbital,andsodium thiopental.

Quinazolinones

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Main article:Quinazolinone
See also:Methaqualone

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 ofcancer.[21]

Examples of quinazolinones includecloroqualone,diproqualone,etaqualone(Aolan, Athinazone, Ethinazone),mebroqualone,Afloqualone(Arofuto),mecloqualone(Nubarene, Casfen), andmethaqualone(Quaalude).

Benzodiazepines

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Main article: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 the sleep time, and, in general, reducing wakefulness.[22][23]Likealcohol,benzodiazepinesare 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 disruptsleep architectureby decreasing sleep time, delaying time to REM sleep, and decreasing deepslow-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 asnitrazepamanddiazepamhave residual effects that may persist into the next day and are, in general, not recommended.[22]

It is not clear as to whether the newnonbenzodiazepinehypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar.[22][28]According to the USAgency 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 UKNational 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 oftraffic collisionsamong driving patients, as well as falls and hip fracture for all older patients.[4][29]

Theirmechanism of actionis primarily atGABAAreceptors.[30]

Nonbenzodiazepines

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Main article:Nonbenzodiazepines

Nonbenzodiazepines are a class ofpsychoactive drugsthat are very "benzodiazepine-like" in nature. Nonbenzodiazepinepharmacodynamicsare almost entirely the same asbenzodiazepinedrugs, 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 includezopiclone(Imovane, Zimovane),eszopiclone(Lunesta),zaleplon(Sonata), andzolpidem(Ambien, Stilnox, Stilnoct). Since thegeneric namesof 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 thattoleranceto nonbenzodiazepines may be slower to develop than withbenzodiazepines.[failed verification]A different team was more skeptical, finding little benefit over benzodiazepines.[34]

Others

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Melatonin

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Melatonin,the hormone produced in thepineal glandin the brain and secreted in dim light and darkness, among its other functions, promotes sleep indiurnalmammals.[35]Ramelteonandtasimelteonaresyntheticanaloguesof melatonin which are also used for sleep-related indications.

Antihistamines

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Main article:H1 antagonist

In common use, the termantihistaminerefers only to compounds that inhibit action at the H1receptor (and not H2,etc.).

Clinically, H1antagonists are used to treat certainallergies.Sedation is a common side-effect, and some H1antagonists, such asdiphenhydramine(Benadryl) anddoxylamine,are also used to treat insomnia.

Second-generation antihistaminescross theblood–brain barrierto 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 thecentral nervous systemeffect of drowsiness.

Antidepressants

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Someantidepressantshave sedating effects.

Examples include:

Serotonin antagonists and reuptake inhibitors
Tricyclic antidepressants
Tetracyclic antidepressants

Antipsychotics

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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 asdyslipidemiaandneutropenia,[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 ofantipsychoticswith sedation as a side effect that are occasionally used for insomnia:[50]

First-generation
Second-generation

Miscellaneous drugs

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Alpha-adrenergic agonist
Cannabinoids
Orexin receptor antagonist
Gabapentinoids

Effectiveness

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A majorsystematic reviewandnetwork meta-analysisof medications for the treatment of insomnia was published in 2022.[51]It found a wide range ofeffect sizes(standardized mean difference(SMD)) in terms of efficacy for insomnia.[51]The assessed medications includedbenzodiazepines(e.g.,temazepam,triazolam,many others) (SMDs 0.58 to 0.83),Z-drugs(eszopiclone,zaleplon,zolpidem,zopiclone) (SMDs 0.03 to 0.63), sedativeantidepressantsandantihistamines(doxepin,doxylamine,trazodone,trimipramine) (SMDs 0.30 to 0.55), theantipsychoticquetiapine(SMD 0.07),orexin receptor antagonists(daridorexant,lemborexant,seltorexant,suvorexant) (SMDs 0.23 to 0.44), andmelatonin receptor agonists(melatonin,ramelteon) (SMDs 0.00 to 0.13).[51]Thecertainty of evidencevaried and ranged from high to very low depending on the medication.[51]Certain medications often used as hypnotics, including the antihistaminesdiphenhydramine,hydroxyzine,andpromethazineand the antidepressantsamitriptylineandmirtazapine,were not included in analyses due to insufficient data.[51]

Risks

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The use of sedative medications in older people generally should be avoided. These medications are associated with poorer health outcomes, includingcognitive decline,and bone fractures.[52]

Therefore, sedatives and hypnotics should be avoided in people with dementia, according to the clinical guidelines known as theMedication 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

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Notes

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  1. ^When used in anesthesia to produce and maintain unconsciousness, "sleep" is metaphorical as there are no regularsleep stagesor 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 shorterelimination half lifethey 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.

References

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Further reading

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Look uphypnoticin Wiktionary, the free dictionary.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Hypnotic&oldid=1251554282"