This is currently being
merged.
After
a discussion, consensus to merge this with content from
Somnifacient was found. You can help implement the merge by following the instructions at
Help:Merging and the resolution on
the discussion. Process started in July 2023.
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]
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).
Barbiturates are drugs that act as
central nervous systemdepressants, 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.
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]
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]
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]
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.[32] 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.[33]
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.[34]Ramelteon and
tasimelteon are
syntheticanalogues of melatonin which are also used for sleep-related indications.
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.
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.[42][43] 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,[44][45][46][47] 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 did not demonstrated any short-term benefits in sleep quality.[48] Examples of
antipsychotics with sedation as a side effect that are occasionally used for insomnia:[49]
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.[51]
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).[52] The use of these medications can further impede cognitive function for people with dementia, who are also more sensitive to side effects of medications.
^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.
^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.
^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.
ISBN978-0-07-146804-6. Retrieved 2014-02-06.
^
abWagner 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.
PMID9640488.
S2CID34250754.
^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.
PMID15531349.
^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.
PMID15003439.
Finkle WD, Der JS, Greenland S, Adams JL, Ridgeway G, Blaschke T, et al. (October 2011). "Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults". Journal of the American Geriatrics Society. 59 (10): 1883–1890.
doi:
10.1111/j.1532-5415.2011.03591.x.
PMID22091502.
S2CID23523742.
Allain H, Bentué-Ferrer D, Polard E, Akwa Y, Patat A (2005). "Postural instability and consequent falls and hip fractures associated with use of hypnotics in the elderly: a comparative review". Drugs & Aging. 22 (9): 749–765.
doi:
10.2165/00002512-200522090-00004.
PMID16156679.
S2CID9296501.
^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.
PMID15746509. 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.
^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.
PMID9640488.
S2CID34250754. 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.
^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.
PMID8019056.
S2CID265772823.
^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.
PMID11465523.
^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.
PMID22973576.
^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.
PMID22510671.
S2CID9888209.
Harrison N, Mendelson WB, de Wit H (2000).
"Barbiturates". In Bloom FE, Kupfer DJ (eds.). Psychopharmacology (The Fourth Generation of Progress ed.). New York: Raven Press. discusses Barbs vs. benzos
Godard M, Barrou Z, Verny M (December 2010). "[Geriatric approach of sleep disorders in the elderly]". Psychologie & Neuropsychiatrie du Vieillissement. 8 (4): 235–241.
doi:
10.1684/pnv.2010.0232.
PMID21147662.