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===Nonbenzodiazepines===
===Nonbenzodiazepines===
{{Details|Nonbenzodiazepines}}
{{Main|Nonbenzodiazepines}}
{{See also|Z-drug}}
{{See also|Z-drug}}


Nonbenzodiazepines are a class of [[psychoactive]] drugs that are very benzodiazepine-like in nature. Nonbenzodiazepines [[pharmacodynamics]] are almost entirely the same as [[benzodiazepine]] drugs and therefore employ 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.<ref>{{cite journal|last1=Siriwardena |first1=A. N. |last2=Qureshi |first2=Z. |last3=Gibson |first3=S. |last4=Collier |first4=S. |last5=Latham |first5=M. |title=GPs' attitudes to benzodiazepine and 'Z-drug' prescribing: a barrier to implementation of evidence and guidance on hypnotics |journal=Br J Gen Pract |volume=56 |issue=533 |pages=964–7 |date=December 2006 |pmid=17132386 |pmc=1934058 |doi=}} {{open access}}</ref><ref>{{cite journal|last1=Wagner |first1=J. |last2=Wagner |first2=M. L. |last3=Hening |first3=W. A. |title=Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia |journal=Ann Pharmacother |volume=32 |issue=6 |pages=680–91 |date=June 1998 |pmid=9640488 |doi=10.1345/aph.17111}}</ref>
⚫
Nonbenzodiazepines have demonstrated efficacy in treating some [[sleep disorders]]. Limited, inconclusive evidence suggests that [[drug tolerance|tolerance]] to nonbenzodiazepines is slower to develop than with [[benzodiazepines]]. Data is also limited with regard to long-term effects of nonbenzodiazepines; further research into the safety and long-term effectiveness of nonbenzodiazepines has been recommended in a review of the literature.<ref>{{cite journal|last=Benca |first=R. M. |title=Diagnosis and treatment of chronic insomnia: a review |journal=Psychiatr Serv |volume=56 |issue=3 |pages=332–43 |date=March 2005 |pmid=15746509 |doi=10.1176/appi.ps.56.3.332 |url=http://ps.psychiatryonline.org/cgi/content/full/56/3/332}}</ref>


Examples include [[zopiclone]] (Imovane/Zimovane), [[eszopiclone]] (Lunesta), [[zaleplon]] (Sonata/Stilnox), and [[zolpidem]] (Ambien).
Examples include [[zopiclone]] (Imovane/Zimovane), [[eszopiclone]] (Lunesta), [[zaleplon]] (Sonata/Stilnox), and [[zolpidem]] (Ambien).

====Comparison to benzodiazepines====
{{OR-section|date=February 2014}}

⚫
Nonbenzodiazepines have demonstrated efficacy in treating some [[sleep disorders]]. Limited, inconclusive evidence suggests that [[drug tolerance|tolerance]] to nonbenzodiazepines is slower to develop than with [[benzodiazepines]]. Data is also limited with regard to long-term effects of nonbenzodiazepines; further research into the safety and long-term effectiveness of nonbenzodiazepines has been recommended in a review of the literature.<ref>{{cite journal|last=Benca |first=R. M. |title=Diagnosis and treatment of chronic insomnia: a review |journal=Psychiatr Serv |volume=56 |issue=3 |pages=332–43 |date=March 2005 |pmid=15746509 |doi=10.1176/appi.ps.56.3.332 |url=http://ps.psychiatryonline.org/cgi/content/full/56/3/332}}</ref>


===Barbiturates===
===Barbiturates===

Revision as of 04:39, 8 February 2014

This article is about the class of prescription medicines. For the state of mind, see Hypnosis. For other uses, see Hypnotic (disambiguation).
Compare with Sedatives.
"Sleeping pills" redirects here. For the 2003 film, see Sleeping Pills (film).

Hypnotic (also called soporific) drugs are a class of psychoactives whose primary function is to induce sleep[1] and to be used in the treatment of insomnia, and in surgical anesthesia. 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. Because drugs in this class generally produce dose-dependent effects, ranging from anxiolysis to production of unconsciousness, they are often referred to collectively as "sedative-hypnotic" drugs.[2] Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries.[3] Many hypnotic drugs are habit-forming and, due to a large number of factors known to disturb the human sleep pattern, a physician may instead recommend alternative sleeping patterns, sleep hygiene, and exercise, before prescribing medication for sleep. Hypnotic medication when prescribed should be used for the shortest period of time possible.[4]

The benzodiazepine and nonbenzodiazepine hypnotic medications also have a number of side effects such as daytime fatigue, and cognitive impairments. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or somnambulism.[5] Elderly people are more sensitive to these side effects and a meta-analysis found that the risks generally outweigh any marginal benefits of hypnotics in the elderly.[6] A review of the literature regarding benzodiazepine hypnotic and Z-drugs concluded that these drugs caused an unjustifiable risk to the individual and to public health, and lack evidence of long-term effectiveness due to tolerance. The risks include dependence, accidents, and other adverse effects. Gradual discontinuation of hypnotics leads to improved health without worsening of sleep. Preferably they should be prescribed for only a few days at the lowest effective dose, and avoided altogether wherever possible in the elderly.[7]

History

Main articles: Barbiturate, Methaqualone, Benzodiazepine, and Nonbenzodiazepine

Research about using medications to treat insomnia evolved throughout the last half of the 20th century. The first class of drugs that emerged were barbiturates in the early 1900s.[8] Unfortunately, overdoses were a risk,[9][10][11] and replacements were sought.

During the 1970s, methaqualones[citation needed] 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; addiction 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.[13]

Nonbenzodiazepines are the most recent development. Although it's clear that they are less toxic than their predecessors, barbiturates, comparative efficacy over benzodiazepines have not been established. Without longitudinal studies, it is hard to determine; however some psychiatrists recommend these drugs, citing research suggesting they are equally potent with less potential for abuse.[14]

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, (generally prescribed to regulate blood pressure) quetiapine, (an antipsychotic) and the over-the-counter sleep aid diphenhydramine (Benadryl; an antihistamine).

As a non-medication alternative, changes in sleep hygiene and natural-based remedies such as chamomile or melatonin (present as a hormone in the brain) can also be used to facilitate sleep.

Types

Benzodiazepines

Template:Main section

See also: List of benzodiazepines

Benzodiazepines (e.g., alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium), and clonazepam (Klonopin)) 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.[15][16]

However, they worsen sleep quality by increasing light sleep and decreasing deep sleep. 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.[17][18] 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.[16] Longer-acting benzodiazepines such as nitrazepam and diazepam have residual effects that may persist into the next day and are, in general, not recommended.[15]

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.[15][18] 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.[18] This may make the non-benzodiazepines preferable as the first-line long-term treatment of insomnia.[16] However, the UK National Institute for Health and Clinical Excellence did not find any convincing evidence in favor of Z-drugs. 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.[15]

Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed to be effective.[19] 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.[19][3]

Nonbenzodiazepines

Main article: Nonbenzodiazepines
See also: Z-drug

Nonbenzodiazepines are a class of psychoactive drugs that are very benzodiazepine-like in nature. Nonbenzodiazepines pharmacodynamics are almost entirely the same as benzodiazepine drugs and therefore employ 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.[20][21]

Examples include zopiclone (Imovane/Zimovane), eszopiclone (Lunesta), zaleplon (Sonata/Stilnox), and zolpidem (Ambien).

Comparison to benzodiazepines

Nonbenzodiazepines have demonstrated efficacy in treating some sleep disorders. Limited, inconclusive evidence suggests that tolerance to nonbenzodiazepines is slower to develop than with benzodiazepines. Data is also limited with regard to long-term effects of nonbenzodiazepines; further research into the safety and long-term effectiveness of nonbenzodiazepines has been recommended in a review of the literature.[22]

Barbiturates

Main article: Barbiturate

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 anticonvulsants. Barbiturates also have analgesic effects; however, these effects are somewhat weak, preventing barbiturates from being used in surgery in the absence of other analgesics. They have addiction potential, both physical and psychological. Barbiturates have now largely been replaced by benzodiazepines in routine medical practice – for example, 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 assisted suicide. Barbiturates are derivatives of barbituric acid.

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

Quinazolinones

Template:Main section

Further information: Methaqualone and on the main drug of this class

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.[23]

Examples of quinazolinones:

Others

Antihistamines

Template:Main section 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 allergic reactions. Sedation is a common side-effect, and some H1 antagonists, such as diphenhydramine 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. This results in them primarily affect 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
Tricyclics
Tetracyclic antidepressants

Antipsychotics

Examples of antipsychotics with sedation as a side effect:[31]

Efficacy

Mechanism of action

More common drugs – including barbiturates, methaqualones, benzodiazepines, and nonbenzodiazepines – work by having an agonistic effect on the GABAA receptor and by acting as positive allosteric modulators;[citation needed] while others – such as antihistamines, 5-HT2A antagonists, anticholinergics, alpha blockers, and dopamine antagonists – have various mechanisms of action.[citation needed]

Examples

Original list (as of a former revision)
Normison 10 mg tablets
Seconal 100 mg capsules
Halcion .25 and .50 mg tablets
Ambien 5 and 10 mg caplets

These drugs include:

See also

References

  1. ^ "Dorlands Medical Dictionary:hypnotic".[dead link]
  2. ^ Brunton, Laurence L.; Lazo, John S.; Lazo Parker, Keith L. (2006). "17: Hypnotics and Sedatives". Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). The McGraw-Hill Companies, Inc. ISBN 0-07-146804-8. Retrieved 2014-02-06.
  3. ^ a b National Prescribing Service (2 February 2010). "NPS News 67: Addressing hypnotic medicines use in primary care". Retrieved 19 March 2010.
  4. ^ Mendels, J. (September 1991). "Criteria for selection of appropriate benzodiazepine hypnotic therapy". J Clin Psychiatry. 52. Suppl: 42–6. PMID 1680126.
  5. ^ Gelder, M.; Mayou, R.; Geddes, J. (2005). Psychiatry (3rd ed.). New York: Oxford. p. 238.
  6. ^ Glass, J.; Lanctôt, K. L.; Herrmann, N.; Sproule, B. A.; Busto, U. E. (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. Open access icon
  7. ^ "What's wrong with prescribing hypnotics?". Drug Ther Bull. 42 (12): 89–93. December 2004. doi:10.1136/dtb.2004.421289. PMID 15587763. {{cite journal}}: Unknown parameter |registration= ignored (|url-access= suggested) (help)
  8. ^ "Barbiturates". Archived from the original on 7 November 2007. Retrieved 2007-10-31. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  9. ^ Whitlock, F. A. (June 14, 1975). "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic". Med J Aust. 1 (24): 737–43. PMID 239307.
  10. ^ Johns, M. W. (1975). "Sleep and hypnotic drugs". Drugs. 9 (6): 448–78. doi:10.2165/00003495-197509060-00004. PMID 238826.
  11. ^ Jufe, G. S. (Jul–August 2007). "[New hypnotics: perspectives from sleep physiology]". Vertex. 18 (74): 294–9. PMID 18265473. {{cite journal}}: Check date values in: |date= (help)
  12. ^ Shorter, Edward (2005). "Benzodiazepines". A Historical Dictionary of Psychiatry. Oxford University Press. pp. 41–2. ISBN 0-19-517668-5. Retrieved 2014-02-06.
  13. ^ Barbera, J.; Shapiro, C. (2005). "Benefit-risk assessment of zaleplon in the treatment of insomnia". Drug Saf. 28 (4): 301–18. doi:10.2165/00002018-200528040-00003. PMID 15783240.
  14. ^ Wagner, J.; Wagner, M. L.; Hening, W. A. (June 1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". Ann Pharmacother. 32 (6): 680–91. doi:10.1345/aph.17111. PMID 9640488.
  15. ^ a b c d "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. Retrieved 2009-07-26.
  16. ^ a b c Ramakrishnan K, Scheid DC (August 2007). "Treatment options for insomnia". American Family Physician. 76 (4): 517–26. PMID 17853625.
  17. ^ D. Maiuro PhD, Roland (13 December 2009). Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research. Springer Publishing Company. pp. 128–30. ISBN 0-8261-1094-0.
  18. ^ a b c Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M (June 2005). "Manifestations and Management of Chronic Insomnia in Adults. Summary, Evidence Report/Technology Assessment: Number 125" (PDF). Agency for Healthcare Research and Quality.{{cite web}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b 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
  20. ^ Siriwardena, A. N.; 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". Br J Gen Pract. 56 (533): 964–7. PMC 1934058. PMID 17132386. Open access icon
  21. ^ Wagner, J.; Wagner, M. L.; Hening, W. A. (June 1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". Ann Pharmacother. 32 (6): 680–91. doi:10.1345/aph.17111. PMID 9640488.
  22. ^ Benca, R. M. (March 2005). "Diagnosis and treatment of chronic insomnia: a review". Psychiatr Serv. 56 (3): 332–43. doi:10.1176/appi.ps.56.3.332. PMID 15746509.
  23. ^ Chen K, Wang K, Kirichian AM; et al. (December 2006). "In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and therapy". Mol. Cancer Ther. 5 (12): 3001–13. doi:10.1158/1535-7163.MCT-06-0465. PMID 17172404. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  24. ^ 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): 331–55. doi:10.2165/00002512-199404040-00006. PMID 8019056.
  25. ^ "Levate (amitriptyline), dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 1 December 2013.
  26. ^ Hajak, G.; Rodenbeck, A.; Voderholzer, U.; Riemann, D.; Cohrs, S.; Hohagen, F.; et al. (2001). "Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study". J Clin Psychiatry. 62 (6): 453–63. doi:10.4088/JCP.v62n0609. PMID 11465523.
  27. ^ Template:Cite isbn[page needed]
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  29. ^ Hartmann, P. M. (January 1999). "Mirtazapine: a newer antidepressant". Am Fam Physician. 59 (1): 159–61. PMID 9917581.
  30. ^ Jindal, R. D. (2009). "Insomnia in patients with depression: some pathophysiological and treatment considerations". CNS Drugs. 23 (4): 309–29. doi:10.2165/00023210-200923040-00004. PMID 19374460.
  31. ^ 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.
  32. ^ Ratti, E.; Carpenter, D. J.; Zamuner, S.; Fernandes, S.; Squassante, L.; Danker-Hopfe, H.; et al. (2013). "Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia". Sleep. doi:10.5665/sleep.3208. PMID 24293756.
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