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==History==
==History==
{{Main|Barbiturates|Benzodiazepines|Nonbenzodiazepines}}
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Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Whereas ancient remedies were non-medicinal or dangerous, scientists sought to change that. The first class of drugs that emerged were called [[barbiturates]] (circa 1930s), and did their job well when compared to chloroform. Addiction was a risk; as was lethality. Benzodiazepines, were later discovered (circa 1950s) and continued to be developed. In many respects, they were advantageous over barbiturates:<ref name="pmid15783240" /> lower doses could be prescribed, they had fewer negative effects, and it was harder to overdose on them.
Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Whereas ancient remedies were non-medicinal or dangerous, scientists sought to change that. The first class of drugs that emerged were [[barbiturates]] in the early 1900s.<ref name="rzepa">{{cite web|url=http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/barbiturate_text.htm|title=Barbiturates|accessdate=2007-10-31|archiveurl=https://web.archive.org/web/20071107090620/http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/barbiturate_text.htm|archivedate=7 November 2007|deadurl=no}}</ref> Unfortunately, overdoses were a risk,<ref>{{cite journal|author=Whitlock FA|date=June 14, 1975|title=Suicide in Brisbane, 1956 to 1973: the drug-death epidemic|journal=Med J Aust|volume=1|issue=24|pages=737–43|pmid=239307}}</ref><ref>{{cite journal|author=Johns MW|year=1975|title=Sleep and hypnotic drugs|journal=Drugs|volume=9|issue=6|pages=448–78|pmid=238826|doi=10.2165/00003495-197509060-00004}}</ref><ref>{{cite journal|author=Jufe GS|date=Jul–August 2007|title=[New hypnotics: perspectives from sleep physiology]|journal=Vertex|volume=18|issue=74|pages=294–9|pmid=18265473}}</ref> and were replaced with the newer class of drugs benzodiazepines by the late 1970s.<ref name=isbn0-19-517668-5>{{cite book |author=Shorter E |title=A Historical Dictionary of Psychiatry |publisher=Oxford University Press |year=2005 |chapter=Benzodiazepines |pages=41–2 |isbn=0-19-517668-5 }}</ref>


Drug research is a developing field, where newer, safer drugs are constantly being developed; yet benzodiazepines have their drawbacks. Addiction is possible, and deaths have occurred (especially when combined with alcohol or other [[depressants]].
Drug research is a developing field, where newer, safer drugs are constantly being developed; yet benzodiazepines have their drawbacks. Addiction is possible, and deaths have occurred (especially when combined with alcohol or other [[depressants]].


Nonbenzodiazepines, or the "Z-drug" family (so named because the drugs in this class all begin with the letter ''Z''), 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 they are hailed by some psychiatrists as equally-potent soporifics with less potential for abuse.
[[Nonbenzodiazepines]], or the "Z-drug" family, 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 they are hailed by some psychiatrists as equally-potent soporifics with less potential for abuse.<ref name="pmid9640488">{{cite journal | author = Wagner J, Wagner ML, Hening WA | title = Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia | journal = Ann Pharmacother | volume = 32 | issue = 6 | pages = 680–91 | year = 1998 | month = June | pmid = 9640488 | doi = 10.1345/aph.17111 }}</ref>


It should be noted that barbiturates, benzodiazepines, and Z-drugs are ''not'' the only remedy for insomnia; psychiatrists sometimes prescribe other medicines [[off-label]] that have sedating effects. Among these are [[mirtazapine]], [[clonidine]], [[quetiapine]], or the over-the-counter sleep aid [[diphenhydramine]].
It should be noted that barbiturates, benzodiazepines, and Z-drugs are ''not'' the only remedy for insomnia; psychiatrists sometimes prescribe other medicines [[off-label]] that have sedating effects. Among these are [[mirtazapine]], [[clonidine]], [[quetiapine]], or the over-the-counter sleep aid [[diphenhydramine]].

Revision as of 08:14, 21 January 2014

This article is about the class of prescription medicines. For the state of mind, see Hypnosis. For other uses, see Hypnotic (disambiguation).
"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 metaanalysis found[undue weight? – discuss] 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: Barbiturates, Benzodiazepines, and Nonbenzodiazepines

Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Whereas ancient remedies were non-medicinal or dangerous, scientists sought to change that. The first class of drugs that emerged were barbiturates in the early 1900s.[8] Unfortunately, overdoses were a risk,[9][10][11] and were replaced with the newer class of drugs benzodiazepines by the late 1970s.[12]

Drug research is a developing field, where newer, safer drugs are constantly being developed; yet benzodiazepines have their drawbacks. Addiction is possible, and deaths have occurred (especially when combined with alcohol or other depressants.

Nonbenzodiazepines, or the "Z-drug" family, 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 they are hailed by some psychiatrists as equally-potent soporifics with less potential for abuse.[13]

It should be noted that barbiturates, benzodiazepines, and Z-drugs are not the only remedy for insomnia; psychiatrists sometimes prescribe other medicines off-label that have sedating effects. Among these are mirtazapine, clonidine, quetiapine, or the over-the-counter sleep aid diphenhydramine.

Benzodiazepines

Further information: Benzodiazepines

Benzodiazepines are the most frequently-prescribed hypnotic medications,

although their use in recent years[vague] is being increasingly replaced by newer nonbenzodiazepine hypnotic drugs and the hormone melatonin.[citation needed] Benzodiazepines are effective in the short term but tolerance to their hypnotic effects develops after 1 or 2 weeks, thus making them ineffective for long-term use.


They are also a cause of hospital admissions, especially in the elderly who are more sensitive to their effects.[3]


When used for extended periods of time, benzodiazepine withdrawal syndrome frequently develops upon discontinuation—a condition marked by symptoms such as insomnia, anxiety, confusion, depersonalization, mood swings and perceptual disturbances.


Benzodiazepine withdrawal is a medical emergency and should be treated as such. It is a common misconception that drugs such as heroin, oxycodone, and other opiates are the most physically dangerous in withdrawal. Benzodiazepine and z-drug dependence can be lethal in withdrawal. To avoid long-term dependence, doctors generally prescribe benzodiazepines (as indicated for sleep) for no more than two weeks.

This purpose is two-fold: it prevents hoarding of drugs and their abuse; and, more importantly, prevents rebound effects—the condition observed when the original disorder (insomnia) worsens after the patient becomes tolerant. Larger and larger doses are required to gain the same effect as the GABA receptors in the brain decrease in number.

Benzodiazepines tend to exert their hypnotic effects at high dosage compared to the more moderate dosage needed for anxiolytic effects to be felt.[14] The downside of the hypnotic properties of benzodiazepines is that they actually worsen the sleep architecture and thus the quality of sleep.[15] They are also associated with an increased risk of road traffic accidents.[16]

Controversies

Case reports that have been quietly accumulating for the past 20 years in the medical literature, demonstrating that some sleeping medications, such as zolpidem (marketed as Ambien in the United States), can induce hallucinations, delusions and psychosis in both psychiatric populations and in individuals without psychiatric conditions.[17][18][19][20]

On another front, a 2012 University of California study shows that use of prescribed sleeping pills increases risk of death by cancer, heart disease and other causes regardless of health status.[21] The 2012 study by University of California, San Diego professor of psychiatry Daniel F. Kripke MD and colleagues, compared 10,500 individuals who took sleeping pills (with 23,500 matched controls) from 2002 to 2007.[22] Individuals who took sleeping pills were at a higher risk for death from all causes even after researchers controlled for age, sex, lifestyle factors and underlying health problems.[21] Prescribed sleeping pills included in this study included benzodiazepines, such as Restoril; non-benzodiazepines, such as Ambien, Intermezzo, Lunesta, and Sonata; barbiturates; and sedative antihistamines [such as diphenhydramine].[21] In a WebMD article, the study's author, Daniel F. Kripke MD[peacock prose] states unambiguously:

"We think these sleeping pills are very dangerous. We think they cause death. We think they cause cancers." And because they are currently so widely used, he concludes, "it is possible but not proven that reducing the use of these pills would lower the U.S. death rate."[23]

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Other options may include the patient learning about sleep hygiene and implementing behavioral changes; reducing stress by possibly seeking less stressful work; learning daytime stress reduction techniques including exercise, techniques in time management, organization and planning; yoga and meditation. Individuals already taking a sleeping pill should talk with their treatment provider before making any medication changes.

Nonbenzodiazepines

Further information: Nonbenzodiazepines

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.[24]

Examples

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".
  2. ^ Brunton, Laurence L; Lazo, John S; Lazo Parker, Keith L (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th Edition (11 ed.). The McGraw-Hill Companies, Inc. ISBN 0-07-146804-8.
  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 (1991). "Criteria for selection of appropriate benzodiazepine hypnotic therapy". J Clin Psychiatry. 52. Suppl: 42–6. PMID 1680126. {{cite journal}}: Unknown parameter |month= ignored (help)
  5. ^ Gelder, M, Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp238.
  6. ^ Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ "What's wrong with prescribing hypnotics?". Drug Ther Bull. 42 (12): 89–93. 2004. doi:10.1136/dtb.2004.421289. PMID 15587763. {{cite journal}}: Unknown parameter |month= ignored (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 FA (June 14, 1975). "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic". Med J Aust. 1 (24): 737–43. PMID 239307.
  10. ^ Johns MW (1975). "Sleep and hypnotic drugs". Drugs. 9 (6): 448–78. doi:10.2165/00003495-197509060-00004. PMID 238826.
  11. ^ Jufe GS (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 E (2005). "Benzodiazepines". A Historical Dictionary of Psychiatry. Oxford University Press. pp. 41–2. ISBN 0-19-517668-5.
  13. ^ Wagner J, Wagner ML, Hening WA (1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". Ann Pharmacother. 32 (6): 680–91. doi:10.1345/aph.17111. PMID 9640488. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Montenegro M, Veiga H, Deslandes A (2005). "[Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study.]". Arq Neuropsiquiatr. 63 (2B): 410–5. doi:10.1590/S0004-282X2005000300009. PMID 16059590. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ 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.
  16. ^ Gustavsen I, Bramness JG, Skurtveit S, Engeland A, Neutel I, Mørland J (2008). "Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam". Sleep Med. 9 (8): 818–22. doi:10.1016/j.sleep.2007.11.011. PMID 18226959. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Bruun TG. (August 30, 1993). "[Abuse potential during use and withdrawal psychosis after treatment with the hypnotic zolpidem (Stilnoct)] Original in Danish". Ugeskr Laeger. 155 (35): 2711–3. PMID 7786333.{{cite journal}}: CS1 maint: postscript (link)
  18. ^ Markowitz JS, Brewerton TD. (1996). "Zolpidem-induced psychosis". Annals of Clinical Psychiatry. 8 (2): 89–91. doi:10.3109/10401239609148806. PMID 8807033. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: postscript (link)
  19. ^ Pitner JK, Gardner M, Neville M, Mintzer J. (1997). "Zolpidem-induced psychosis in an older woman". J Am Geriatr Soc. 45 (4): 533–4. PMID 9100733. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: postscript (link)
  20. ^ Chiung-Lei H, Ching-Jui C, Ching-Feng H, Hsi-Len L. (2003). "Zolpidem-induced distortion in visual perception". Annals of Pharmacotherapy. 37 (5): 683–86. doi:10.1345/aph.1C318. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: postscript (link)
  21. ^ a b c "Prescription Sleeping Pills tied to Increased Death, Cancer". Retrieved 2013-01-24.
  22. ^ Kripke DF, Langer RD, Kline LE. (2012). "Hypnotics' association with mortality or cancer: a matched cohort study". British Journal of Medicine Open (BMJ Open). 2 (e000850): . doi:10.1136/bmjopen-2012-000850. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: postscript (link)
  23. ^ DeNoon DJ (27 February 2012). "Sleeping Pills Called 'as Risky as Cigarettes': Study Links Sleeping Pills to 4.6-Fold Higher Death Risk". Retrieved 23 January 2013.
  24. ^ Benca RM (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ Ratti, E. "Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia". Sleep. (2013). PMID http://www.ncbi.nlm.nih.gov./pubmed/24293756. {{cite journal}}: Check |pmid= value (help); External link in |pmid= (help)

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