Editing Benzodiazepine (section)

==Medical uses==
{{See also|List of benzodiazepines}}
[[File:Midazolam.JPG|thumb|alt=Two 10 mL bottles labeled Midazolam. The bottle on the left has a label in red and says 1 mg/mL; the one on the right is in green and says 5 mg/mL. Both bottles have much fine print.|[[Midazolam]] 1 & 5 mg/mL [[Drug injection|injections]] (Canada)]]
Benzodiazepines possess [[psycholeptic]], [[sedative]], [[hypnotic]], [[anxiolytic]], anticonvulsant, [[muscle relaxant]], and [[anterograde amnesia|amnesic]] actions,<ref name=ip2002>{{cite book |vauthors=Page C, Michael C, Sutter M, Walker M, Hoffman BB |title=Integrated Pharmacology |edition=2nd |year=2002 |publisher=C.V. Mosby |isbn=978-0-7234-3221-0 }}</ref><ref name=pmid18175099>{{cite book | vauthors = Olkkola KT, Ahonen J | chapter = Midazolam and Other Benzodiazepines |editor1=Schüttler J |editor2=Schwilden H |title = Modern Anesthetics | series = Handbook of Experimental Pharmacology | volume = 182 | issue = 182 | pages = 335–360 | year = 2008 | pmid = 18175099 | doi = 10.1007/978-3-540-74806-9_16 | isbn = 978-3-540-72813-9 }}</ref> which are useful in a variety of indications such as [[alcohol dependence]], [[seizures]], [[anxiety disorders]], [[panic]], [[psychomotor agitation|agitation]], and insomnia. Most are administered orally; however, they can also be given [[intravenous therapy|intravenously]], [[intramuscular injection|intramuscularly]], or [[Rectal administration|rectally]].<ref name="BNF_2009">{{cite book |title=British National Formulary (BNF 57) |publisher=Royal Pharmaceutical Society of Great Britain |year=2009 |isbn=978-0-85369-845-6 |title-link=British National Formulary }}</ref>{{rp|189|date=November 2012}} In general, benzodiazepines are well tolerated and are safe and effective drugs in the short term for a wide range of conditions.<ref name=Perugi>{{cite journal | vauthors = Perugi G, Frare F, Toni C | title = Diagnosis and treatment of agoraphobia with panic disorder | journal = CNS Drugs | volume = 21 | issue = 9 | pages = 741–764 | year = 2007 | pmid = 17696574 | doi = 10.2165/00023210-200721090-00004 | s2cid = 43437233 }}</ref><ref name=Tesar>{{cite journal | vauthors = Tesar GE | title = High-potency benzodiazepines for short-term management of panic disorder: the U.S. experience | journal = The Journal of Clinical Psychiatry | volume = 51 | issue = Suppl | pages = 4–10; discussion 50–53 | date = May 1990 | pmid = 1970816 }}</ref> Tolerance can develop to their effects and there is also a risk of [[drug dependence|dependence]], and upon discontinuation a withdrawal syndrome may occur. These factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability.<ref>{{cite journal | vauthors = Faught E | title = Treatment of refractory primary generalized epilepsy | journal = Reviews in Neurological Diseases | volume = 1 | issue = Suppl 1 | pages = S34–43 | year = 2004 | pmid = 16400293 }}</ref><ref>{{cite journal | vauthors = Allgulander C, Bandelow B, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP | title = WCA recommendations for the long-term treatment of generalized anxiety disorder | journal = CNS Spectrums | volume = 8 | issue = Suppl 1 | pages = 53–61 | date = August 2003 | pmid = 14767398 | doi = 10.1017/S1092852900006945 | s2cid = 32761147 }}</ref> [[Long-term effects of benzodiazepines|The effects of long-term use]] or misuse include the tendency to cause or worsen [[cognitive deficit]]s, depression, and anxiety.<ref name=tdamobd2004>{{cite journal | vauthors = Ashton H | title = The diagnosis and management of benzodiazepine dependence | journal = Current Opinion in Psychiatry | volume = 18 | issue = 3 | pages = 249–255 | date = May 2005 | pmid = 16639148 | doi = 10.1097/01.yco.0000165594.60434.84 | s2cid = 1709063 | url = https://www.benzo.org.uk/amisc/ashdiag.pdf }}</ref><ref name=ohop/> The [[College of Physicians and Surgeons of British Columbia]] recommends discontinuing the usage of benzodiazepines in those on opioids and those who have used them long term.<ref>{{cite web | url = https://www.cpsbc.ca/for-physicians/college-connector/2016-V04-01/07 | title = Benzodiazepines in chronic pain | date = February 2016 | access-date = 22 September 2016 | archive-date = 23 September 2016 | archive-url = https://web.archive.org/web/20160923185441/https://www.cpsbc.ca/for-physicians/college-connector/2016-V04-01/07 | url-status = dead }}</ref> Benzodiazepines can have serious adverse health outcomes, and these findings support clinical and regulatory efforts to reduce usage, especially in combination with non-benzodiazepine receptor agonists.<ref name=":0" />

===Panic disorder===
{{Further|Panic disorder}}
[[File:Lorazepam Orion.jpg|thumb|A box of Lorazepam Orion (Lorazepam) tablets]]

Benzodiazepines are usually administered orally; however, very occasionally [[lorazepam]] or [[diazepam]] may be given intravenously for the treatment of [[panic attack]]s.<ref name="BNF_2009"/>

Because of their effectiveness, tolerability, and rapid onset of [[anxiolytic]] action, benzodiazepines are frequently used for the treatment of [[anxiety]] associated with [[panic disorder]].<ref name="pmid15762816">{{cite journal | vauthors = Stevens JC, Pollack MH | title = Benzodiazepines in clinical practice: consideration of their long-term use and alternative agents | journal = The Journal of Clinical Psychiatry | volume = 66 | issue = Suppl 2 | pages = 21–27 | year = 2005 | pmid = 15762816 | quote = The frequent use of benzodiazepines for the treatment of anxiety is likely a reflection of their effectiveness, rapid onset of anxiolytic effect, and tolerability. }}</ref> However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder. The views range from those holding benzodiazepines are not effective long-term<ref name=cgftmamoa2004/> and should be reserved for treatment-resistant cases<ref>{{cite journal | vauthors = Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ | title = World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders | journal = The World Journal of Biological Psychiatry | volume = 3 | issue = 4 | pages = 171–199 | date = October 2002 | pmid = 12516310 | doi = 10.3109/15622970209150621 | s2cid = 922780 | doi-access = free | title-link = doi }}</ref> to those holding they are as effective in the long term as [[selective serotonin reuptake inhibitors]] (SSRIs).<ref name=APA/>

[[American Psychiatric Association]] (APA) guidelines, published in January 2009,<ref name="APA">{{cite web |url=http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=PanicDisorder_2e_PracticeGuideline |format = PDF |title= APA Practice Guideline for the Treatment of Patients With Panic Disorder, Second Edition |publisher=Work Group on Panic Disorder |date=January 2009 |access-date=12 July 2009 }}</ref> note that, in general, benzodiazepines are well tolerated, and their use for the initial treatment for panic disorder is strongly supported by numerous controlled trials. APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another. The choice of treatment between benzodiazepines, SSRIs, [[serotonin–norepinephrine reuptake inhibitors]] (SNRIs), [[tricyclic antidepressant]]s, and psychotherapy should be based on the patient's history, preference, and other individual characteristics. Selective serotonin reuptake inhibitors are likely to be the best choice of pharmacotherapy for many patients with panic disorder, but benzodiazepines are also often used, and some studies suggest that these medications are still used with greater frequency than the SSRIs. One advantage of benzodiazepines is that they alleviate the anxiety symptoms much more quickly than antidepressants, and therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing [[benzodiazepine dependence]]. APA does not recommend benzodiazepines for persons with depressive symptoms or a recent history of [[substance use disorder]]. APA guidelines state that, in general, pharmacotherapy of panic disorder should be continued for at least a year, and that clinical experience supports continuing benzodiazepine treatment to prevent recurrence. Although major concerns about benzodiazepine tolerance and withdrawal have been raised, there is no evidence for significant dose escalation in patients using benzodiazepines long-term. For many such patients, stable doses of benzodiazepines retain their efficacy over several years.<ref name=APA/>

Guidelines issued by the UK-based [[National Institute for Health and Clinical Excellence]] (NICE), carried out a systematic review using different methodology and came to a different conclusion. They questioned the accuracy of studies that were not placebo-controlled. And, based on the findings of [[placebo-controlled studies]], they do not recommend use of benzodiazepines beyond two to four weeks, as tolerance and [[physical dependence]] develop rapidly, with withdrawal symptoms including [[rebound anxiety]] occurring after six weeks or more of use.<ref name=cgftmamoa2004>{{cite web |vauthors=McIntosh A, Cohen A, Turnbull N, Esmonde L, Dennis P, Eatock J, Feetam C, Hague J, Hughes I, Kelly J, Kosky N |title=Clinical guidelines and evidence review for panic disorder and generalised anxiety disorder |url=http://www.nice.org.uk/nicemedia/pdf/cg022fullguideline.pdf |publisher=National Collaborating Centre for Primary Care |year=2004 |access-date=16 June 2009 |archive-date=19 February 2009 |archive-url=https://web.archive.org/web/20090219140855/http://www.nice.org.uk/nicemedia/pdf/cg022fullguideline.pdf |url-status=dead }}</ref><ref>{{cite web |vauthors=Barbui C, Cipriani A |title=Proposal for the inclusion in the WHO Model List of Essential Medicines of a selective serotonin-reuptake inhibitor for Generalised Anxiety Disorder |url=http://who.int/selection_medicines/committees/expert/17/application/Section24_GAD.pdf |publisher=WHO Collaborating Centre for Research and Training in Mental Health |year=2009 |access-date=23 June 2009 |archive-date=5 May 2012 |archive-url=https://web.archive.org/web/20120505191411/http://who.int/selection_medicines/committees/expert/17/application/Section24_GAD.pdf |url-status=dead }}</ref> Nevertheless, benzodiazepines are still prescribed for long-term treatment of [[anxiety disorders]], although specific [[antidepressants]] and psychological therapies are recommended as the [[first-line treatment]] options with the [[anticonvulsant]] drug [[pregabalin]] indicated as a second- or third-line treatment and suitable for long-term use.<ref>{{cite journal | vauthors = Cloos JM, Ferreira V | title = Current use of benzodiazepines in anxiety disorders | journal = Current Opinion in Psychiatry | volume = 22 | issue = 1 | pages = 90–95 | date = January 2009 | pmid = 19122540 | doi = 10.1097/YCO.0b013e32831a473d | s2cid = 20715355 }}</ref> NICE stated that long-term use of benzodiazepines for panic disorder with or without [[agoraphobia]] is an unlicensed indication, does not have long-term efficacy, and is, therefore, not recommended by clinical guidelines. Psychological therapies such as [[cognitive behavioural therapy]] are recommended as a first-line therapy for panic disorder; benzodiazepine use has been found to interfere with therapeutic gains from these therapies.<ref name=cgftmamoa2004 />

===Generalized anxiety disorder===
{{Further|Generalized anxiety disorder}}
[[File:Boites d'alprazolam444.jpg|thumb|Alprazolam pills in boxes, as sold in [[France]]; both the original [[Pfizer]] brand product Xanax and various [[Generic drug|generic forms]] of alprazolam are depicted here.]]

Benzodiazepines have robust efficacy in the short-term management of [[generalized anxiety disorder]] (GAD) when standardized measures of anxiety are used as the outcome variable,<ref>{{cite journal | vauthors = Stimpfl JN, Mills JA, Strawn JR | title = Pharmacologic predictors of benzodiazepine response trajectory in anxiety disorders: a Bayesian hierarchical modeling meta-analysis | journal = CNS Spectrums | volume = 28 | issue = 1 | pages = 53–60 | date = February 2023 | pmid = 34593077 | pmc = 8971141 | doi = 10.1017/S1092852921000870 }}</ref> but did not demonstrate a favorable dropout rate compared to placebo in one meta-analysis.<ref name="pmid17881433">{{cite journal | vauthors = Martin JL, Sainz-Pardo M, Furukawa TA, Martín-Sánchez E, Seoane T, Galán C | title = Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and meta-analysis of clinical trials | journal = Journal of Psychopharmacology | volume = 21 | issue = 7 | pages = 774–782 | date = September 2007 | pmid = 17881433 | doi = 10.1177/0269881107077355 | s2cid = 1879448 }}</ref> A newer meta-analysis showed that benzodiazepines are significantly more effective than serotonergic agents, regardless of treatment length.<ref name="pmid29806492">{{cite journal | vauthors = Gomez AF, Barthel AL, Hofmann SG | title = Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review | journal = Expert Opinion on Pharmacotherapy | volume = 19 | issue = 8 | pages = 883–894 | date = June 2018 | pmid = 29806492 | pmc = 6097846 | doi = 10.1080/14656566.2018.1472767 }}</ref> More research is needed, but unfortunately, newer randomized controlled trials are scarce for the off patent benzodiazepines. According to [[National Institute for Health and Clinical Excellence]] (NICE), benzodiazepines can be used in the immediate management of GAD, if necessary. However, they should not usually be given for longer than 2–4 weeks. The only medications NICE recommends for the longer term management of GAD are antidepressants.<ref name=NICECG022>{{cite web |title=Clinical Guideline 22 (amended). Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care |pages=23–25 |url=http://www.nice.org.uk/nicemedia/pdf/CG022NICEguidelineamended.pdf |publisher=National Institute for Health and Clinical Excellence |year=2007 |access-date=8 August 2009 |archive-url=https://web.archive.org/web/20120514111817/http://www.nice.org.uk/nicemedia/pdf/CG022NICEguidelineamended.pdf |archive-date=14 May 2012 |url-status=dead }}</ref>

Likewise, Canadian Psychiatric Association (CPA) recommends benzodiazepines [[alprazolam]], [[bromazepam]], lorazepam, and diazepam only as a second-line choice, if the treatment with two different antidepressants was unsuccessful.<ref name="pmid16933543">{{cite journal |author=Canadian Psychiatric Association |date=July 2006 |title=Clinical practice guidelines. Management of anxiety disorders |url=http://publications.cpa-apc.org/media.php?mid=440 |url-status=dead |journal=The Canadian Journal of Psychiatry |type=PDF |volume=51 |issue=8 Suppl 2 |pages=9S–91S |pmid=16933543 |archive-url=https://web.archive.org/web/20100714202950/http://publications.cpa-apc.org/media.php?mid=440 |archive-date=14 July 2010 |access-date=8 August 2009}}</ref> Although they are second-line agents, benzodiazepines can be used for a limited time to relieve severe anxiety and agitation. CPA guidelines state that after 4–6 weeks the effect of benzodiazepines may decrease to the level of placebo,<ref name="pmid16933543" /> and that benzodiazepines are less effective than antidepressants in alleviating [[rumination (psychology)|ruminative worry]], the core symptom of GAD, but that in some cases, a prolonged treatment with benzodiazepines as the add-on to an antidepressant may be justified. Evidence from reviews of benzodiazepine tolerance mechanisms<ref name=":2" /> and clonazepam use in psychiatric disorders<ref name="pmid16528135" /> is strongly discordant with the claim that benzodiazepines lose anxiolytic efficacy over a period of weeks, as these reviews present RCT evidence of continued anxiolytic efficacy at up to 22 weeks<ref name=":3" /> and observational (open-label) evidence of continued efficacy at up to 3 years.<ref name=":4" />

A 2015 review found a larger effect with medications than talk therapy.<ref name=Band2015>{{cite journal | vauthors = Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D | title = Efficacy of treatments for anxiety disorders: a meta-analysis | journal = International Clinical Psychopharmacology | volume = 30 | issue = 4 | pages = 183–192 | date = July 2015 | pmid = 25932596 | doi = 10.1097/YIC.0000000000000078 | s2cid = 24088074 }}</ref> Medications with benefit include [[serotonin-noradrenaline reuptake inhibitors]], benzodiazepines, and [[selective serotonin reuptake inhibitors]].<ref name=Band2015/>

===Insomnia===
{{Further|Insomnia}}
[[File:Normison.jpg|thumb|[[Temazepam]] (Normison) 10 mg tablets]]
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. The Committee on Safety of Medicines report recommended that where long-term use of benzodiazepines for insomnia is indicated then treatment should be intermittent wherever possible.<ref>{{cite web|url= http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con2024428.pdf|archive-url= http://webarchive.nationalarchives.gov.uk/20141206140040/http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con2024428.pdf|url-status= dead|archive-date= 6 December 2014|title= Current problems|date= 1988|website= www.mhra.gov.uk|access-date= 21 March 2020}}</ref> 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.<ref name="nice-hypnotics">{{cite web|title=Technology Appraisal Guidance 77. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia |url=http://www.nice.org.uk/nicemedia/pdf/TA077fullguidance.pdf |publisher=National Institute for Clinical Excellence |date=April 2004 |access-date=26 July 2009 |url-status=dead |archive-url=https://web.archive.org/web/20081203063917/http://www.nice.org.uk/nicemedia/pdf/TA077fullguidance.pdf |archive-date=3 December 2008 }}</ref><ref name="pmid17853625">{{cite journal | vauthors = Ramakrishnan K, Scheid DC | title = Treatment options for insomnia | journal = American Family Physician | volume = 76 | issue = 4 | pages = 517–526 | date = August 2007 | pmid = 17853625 | url = http://www.aafp.org/afp/2007/0815/p517.html }}</ref> 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.<ref name="handbook_of_integrative">{{cite book | vauthors = Carlstedt RA | title = Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research | date = 13 December 2009 | publisher = Springer Publishing Company | url = https://books.google.com/books?id=4Tkdm1vRFbUC | isbn = 978-0-8261-1094-7 | pages = 128–130 }}</ref><ref name="ahrq"/>

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 varies between countries.<ref name="pmid17853625"/> Longer-acting benzodiazepines such as [[nitrazepam]] and [[diazepam]] have residual effects that may persist into the next day and are, in general, not recommended.<ref name="nice-hypnotics"/>

Since the release of [[nonbenzodiazepines]], also known as z-drugs, in 1992 in response to safety concerns, individuals with insomnia and other sleep disorders have increasingly been prescribed nonbenzodiazepines (2.3% in 1993 to 13.7% of Americans in 2010), less often prescribed benzodiazepines (23.5% in 1993 to 10.8% in 2010).<ref name="Kaufmann_2016">{{cite journal | vauthors = Kaufmann CN, Spira AP, Alexander GC, Rutkow L, Mojtabai R | title = Trends in prescribing of sedative-hypnotic medications in the USA: 1993–2010 | journal = Pharmacoepidemiology and Drug Safety | volume = 25 | issue = 6 | pages = 637–645 | date = June 2016 | pmid = 26711081 | pmc = 4889508 | doi = 10.1002/pds.3951 }}</ref><ref>{{cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/019908_S000_AP&AE_LTRS&FPL.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/019908_S000_AP&AE_LTRS&FPL.pdf |archive-date=9 October 2022 |url-status=live|title=Approval letter for Ambien|website=Food and Drug Administration}}</ref> It is not clear as to whether the new [[nonbenzodiazepine|non benzodiazepine]] hypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar.<ref name="nice-hypnotics"/><ref name="ahrq"/> 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.<ref name="ahrq">{{cite web |vauthors=Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M |title=Manifestations and Management of Chronic Insomnia in Adults. Summary, Evidence Report/Technology Assessment: Number 125 | publisher = Agency for Healthcare Research and Quality |date=June 2005 |url=http://www.ahrq.gov/clinic/epcsums/insomnsum.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.ahrq.gov/clinic/epcsums/insomnsum.pdf |archive-date=9 October 2022 |url-status=live }}</ref> Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia.<ref name="pmid17853625"/> 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.<ref name="nice-hypnotics"/>

Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed.<ref name="AGSfive"/> When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence that shows twice the incidence of [[traffic collisions]] among driving patients, and falls and hip fracture for older patients.<ref name="AGSfive">{{cite journal |author1 = American Geriatrics Society |author1-link = American Geriatrics Society |title = Five Things Physicians and Patients Should Question |journal = Choosing Wisely: An Initiative of the ABIM Foundation |url = http://www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society/ |access-date = 1 August 2013 |archive-date = 1 September 2013 |archive-url = https://web.archive.org/web/20130901100140/http://www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society/ |url-status = dead }}, which cites</ref><ref name="pmid16156679"/><ref>{{cite journal | publisher = American Geriatrics Society 2012 Beers Criteria Update Expert Panel | title = American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults | journal = Journal of the American Geriatrics Society | volume = 60 | issue = 4 | pages = 616–631 | date = April 2012 | pmid = 22376048 | pmc = 3571677 | doi = 10.1111/j.1532-5415.2012.03923.x | vauthors = Fick D, Semla T, Beizer J, Brandt N, Dombrowski R, DuBeau CE, Flanagan N, Hanlon J, Hollmann P, Linnebur S, Nau D, Rehm B, Sandhu S, Steinman M | collaboration = American Geriatrics Society 2012 Beers Criteria Update Expert Panel }}</ref>

===Seizures===
{{Further|Seizure}}
[[File:Diazepam 10mg-2ml vial yellow background.jpg|thumb|Diazepam 10mg/2ml vial]]

Prolonged convulsive [[epileptic seizure]]s are a [[medical emergency]] that can usually be dealt with effectively by administering fast-acting benzodiazepines, which are potent [[anticonvulsants]]. In a hospital environment, [[intravenous]] [[clonazepam]], [[lorazepam]], and [[diazepam]] are first-line choices. In the community, intravenous administration is not practical and so [[rectal]] diazepam or [[buccal mucosa|buccal]] [[midazolam]] are used, with a preference for midazolam as its administration is easier and more socially acceptable.<ref name=SIGN70>{{cite web |url=http://sign.ac.uk/pdf/sign70.pdf |title=Diagnosis and management of epilepsy in adults |access-date=5 June 2009 |publisher=Scottish Intercollegiate Guidelines Network |year=2005 |pages=17–19 |archive-url=https://web.archive.org/web/20090126152302/http://sign.ac.uk/pdf/sign70.pdf |archive-date=26 January 2009 |url-status=dead }}</ref><ref name=NICECG020>{{cite book |url=http://www.nice.org.uk/nicemedia/pdf/CG020fullguideline.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.nice.org.uk/nicemedia/pdf/CG020fullguideline.pdf |archive-date=9 October 2022 |url-status=live |title=Clinical Guidelines and Evidence Review for the Epilepsies: diagnosis and management in adults and children in primary and secondary care |access-date=2 June 2009 |vauthors=Stokes T, Shaw EJ, Juarez-Garcia A, Camosso-Stefinovic J, Baker R |date=October 2004 |publisher=Royal College of General Practitioners |pages=61, 64–65 | location = London }}</ref>

When benzodiazepines were first introduced, they were enthusiastically adopted for treating all forms of [[epilepsy]]. However, drowsiness and [[drug tolerance|tolerance]] become problems with continued use and none are now considered [[first-line treatment|first-line]] choices for long-term epilepsy therapy.<ref name="pmid19298435">{{cite journal | vauthors = Shorvon SD | title = Drug treatment of epilepsy in the century of the ILAE: the second 50 years, 1959-2009 | journal = Epilepsia | volume = 50 | issue = Suppl 3 | pages = 93–130 | date = March 2009 | pmid = 19298435 | doi = 10.1111/j.1528-1167.2009.02042.x | s2cid = 20445985 | doi-access = free | title-link = doi }}</ref> [[Clobazam]] is widely used by specialist epilepsy clinics worldwide and clonazepam is popular in the Netherlands, Belgium and France.<ref name="pmid19298435"/> Clobazam was approved for use in the United States in 2011. In the UK, both clobazam and clonazepam are second-line choices for treating many forms of epilepsy.<ref name=NICECG020b>{{cite web |url=http://www.nice.org.uk/nicemedia/pdf/CG020fullguideline_appendixB.pdf |title=Clinical Guidelines and Evidence Review for the Epilepsies: diagnosis and management in adults and children in primary and secondary care (Appendix B) |access-date=2 June 2009 |vauthors=Stokes T, Shaw EJ, Juarez-Garcia A, Camosso-Stefinovic J, Baker R |date=October 2004 |publisher=Royal College of General Practitioners |page=432 |location=London |archive-url=https://web.archive.org/web/20111127113914/http://www.nice.org.uk/nicemedia/pdf/CG020fullguideline_appendixB.pdf |archive-date=27 November 2011 |url-status=dead }}</ref> Clobazam also has a useful role for very short-term seizure [[prophylaxis]] and in [[catamenial epilepsy]].<ref name="pmid19298435"/> Discontinuation after long-term use in epilepsy requires additional caution because of the risks of rebound seizures. Therefore, the dose is slowly tapered over a period of up to six months or longer.<ref name=NICECG020/>

===Alcohol withdrawal===
{{Further|Alcohol detoxification}}
[[File:Liverty 10mg.jpg|thumb|Chlordiazepoxide 10 mg pill]]

[[Chlordiazepoxide]] is the most commonly used benzodiazepine for [[alcohol detoxification]],<ref name="pmid9270461">{{cite journal | vauthors = Ashworth M, Gerada C | title = ABC of mental health. Addiction and dependence – II: Alcohol | journal = BMJ | volume = 315 | issue = 7104 | pages = 358–360 | date = August 1997 | pmid = 9270461 | pmc = 2127236 | doi = 10.1136/bmj.315.7104.358 }}</ref> but [[diazepam]] may be used as an alternative. Both are used in the detoxification of individuals who are motivated to stop drinking, and are prescribed for a short period of time to reduce the risks of developing tolerance and dependence to the benzodiazepine medication itself.<ref name="BNF_2009"/>{{rp|275|date=November 2012}} The benzodiazepines with a longer half-life make detoxification more tolerable, and dangerous (and potentially lethal) alcohol withdrawal effects are less likely to occur. On the other hand, short-acting benzodiazepines may lead to [[Causes of seizures#Breakthrough seizure|breakthrough seizures]], and are, therefore, not recommended for detoxification in an outpatient setting. [[Oxazepam]] and [[lorazepam]] are often used in patients at risk of drug accumulation, in particular, the elderly and those with [[cirrhosis]], because they are metabolized differently from other benzodiazepines, through [[Glucuronidation|conjugation]].<ref>{{cite journal | vauthors = Kraemer KL, Conigliaro J, Saitz R | title = Managing alcohol withdrawal in the elderly | journal = Drugs & Aging | volume = 14 | issue = 6 | pages = 409–425 | date = June 1999 | pmid = 10408740 | doi = 10.2165/00002512-199914060-00002 | s2cid = 2724630 }}</ref><ref>{{cite journal | vauthors = Prater CD, Miller KE, Zylstra RG | title = Outpatient detoxification of the addicted or alcoholic patient | journal = American Family Physician | volume = 60 | issue = 4 | pages = 1175–1183 | date = September 1999 | pmid = 10507746 }}</ref>

Benzodiazepines are the preferred choice in the management of [[alcohol withdrawal syndrome]], in particular, for the prevention and treatment of the dangerous complication of seizures and in subduing severe [[delirium]].<ref>{{cite journal | vauthors = Ebell MH | title = Benzodiazepines for alcohol withdrawal | journal = American Family Physician | volume = 73 | issue = 7 | pages = 1191 | date = April 2006 | pmid = 16623205 }}</ref> Lorazepam is the only benzodiazepine with predictable intramuscular absorption and it is the most effective in preventing and controlling acute seizures.<ref>{{cite journal | vauthors = Peppers MP | title = Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease | journal = Pharmacotherapy | volume = 16 | issue = 1 | pages = 49–57 | year = 1996 | pmid = 8700792 | doi = 10.1002/j.1875-9114.1996.tb02915.x | s2cid = 1389910 | url = https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/j.1875-9114.1996.tb02915.x | access-date = 1 February 2020 | archive-date = 15 January 2020 | archive-url = https://web.archive.org/web/20200115181651/https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/j.1875-9114.1996.tb02915.x | url-status = dead }}</ref>

===Other indications===
Benzodiazepines are often prescribed for a wide range of conditions:
* They can sedate patients receiving [[mechanical ventilation]] or those in extreme distress. Caution is exercised in this situation due to the risk of [[respiratory depression]], and it is recommended that [[benzodiazepine overdose]] treatment facilities should be available.<ref>{{cite journal | vauthors = Devlin JW, Roberts RJ | title = Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids | journal = Critical Care Clinics | volume = 25 | issue = 3 | pages = 431–49, vii | date = July 2009 | pmid = 19576523 | doi = 10.1016/j.ccc.2009.03.003 }}</ref> They have also been found to increase the likelihood of later PTSD after people have been removed from ventilators.<ref>{{cite journal | vauthors = Parker AM, Sricharoenchai T, Raparla S, Schneck KW, Bienvenu OJ, Needham DM | title = Posttraumatic stress disorder in critical illness survivors: a metaanalysis | journal = Critical Care Medicine | volume = 43 | issue = 5 | pages = 1121–1129 | date = May 2015 | pmid = 25654178 | doi = 10.1097/CCM.0000000000000882 | s2cid = 11478971 }}</ref>
*Benzodiazepines are indicated in the management of breathlessness (shortness of breath) in advanced diseases, in particular where other treatments have failed to adequately control symptoms.<ref>{{cite journal | vauthors = Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C | title = Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD007354 | date = October 2016 | issue = 10 | pmid = 27764523 | pmc = 6464146 | doi = 10.1002/14651858.CD007354.pub3 }}</ref>
* Benzodiazepines are effective as medication given a couple of hours before surgery to relieve anxiety. They also produce [[amnesia]], which can be useful, as patients may not remember unpleasantness from the procedure.<ref name="Broscheit-2008">{{cite journal | vauthors = Broscheit J, Kranke P | title = [The preoperative medication: background and specific indications for the selection of the drugs] | journal = Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie | volume = 43 | issue = 2 | pages = 134–143 | date = February 2008 | pmid = 18293248 | doi = 10.1055/s-2008-1060547 | s2cid = 259982203 }}</ref> They are also used in patients with [[dental phobia]] as well as some ophthalmic procedures like refractive surgery; although such use is controversial and only recommended for those who are very anxious.<ref>{{cite journal | vauthors = Berthold C | title = Enteral sedation: safety, efficacy, and controversy | journal = Compendium of Continuing Education in Dentistry | volume = 28 | issue = 5 | pages = 264–271; quiz 272, 282 | date = May 2007 | pmid = 17607891 }}</ref> Midazolam is the most commonly prescribed for this use because of its strong sedative actions and fast recovery time, as well as its water solubility, which reduces pain upon injection. Diazepam and lorazepam are sometimes used. Lorazepam has particularly marked amnesic properties that may make it more effective when amnesia is the desired effect.<ref name="BNF_2009"/>{{rp|693|date=November 2012}}
* Benzodiazepines are well known for their strong muscle-relaxing properties and can be useful in the treatment of muscle spasms,<ref name="BNF_2009"/>{{rp|577–578|date=November 2012}} although tolerance often develops to their muscle relaxant effects.<ref name=tdamobd2004 /> [[Baclofen]]<ref>{{cite journal | vauthors = Mañon-Espaillat R, Mandel S | title = Diagnostic algorithms for neuromuscular diseases | journal = Clinics in Podiatric Medicine and Surgery | volume = 16 | issue = 1 | pages = 67–79 | date = January 1999 | doi = 10.1016/S0891-8422(23)00935-7 | pmid = 9929772 | s2cid = 12493035 }}</ref> or [[tizanidine]] are sometimes used as an alternative to benzodiazepines. Tizanidine has been found to have superior tolerability compared to diazepam and baclofen.<ref name="Kamen-2008">{{cite journal | vauthors = Kamen L, Henney HR, Runyan JD | title = A practical overview of tizanidine use for spasticity secondary to multiple sclerosis, stroke, and spinal cord injury | journal = Current Medical Research and Opinion | volume = 24 | issue = 2 | pages = 425–439 | date = February 2008 | pmid = 18167175 | doi = 10.1185/030079908X261113 | s2cid = 73086671 }}</ref>
* Benzodiazepines are also used to treat the acute panic caused by [[hallucinogen]] intoxication.<ref>{{cite book |vauthors=Wyatt JP, Illingworth RN, Robertson CE, Clancy MJ, Munro PT |title=Oxford Handbook of Accident and Emergency Medicine |edition=2nd |year=2005 |publisher=Oxford University Press |isbn=978-0-19-852623-0 |pages=173–208 |chapter=Poisoning }}</ref> Benzodiazepines are also used to calm the acutely agitated individual and can, if required, be given via an intramuscular injection.<ref>{{cite journal | vauthors = Zimbroff DL | title = Pharmacological control of acute agitation: focus on intramuscular preparations | journal = CNS Drugs | volume = 22 | issue = 3 | pages = 199–212 | year = 2008 | pmid = 18278976 | doi = 10.2165/00023210-200822030-00002 | s2cid = 73223621 }}</ref> They can sometimes be effective in the short-term treatment of psychiatric emergencies such as acute [[psychosis]] as in [[schizophrenia]] or [[mania]], bringing about rapid tranquillization and sedation until the effects of [[Lithium pharmacology|lithium]] or [[neuroleptics]] (antipsychotics) take effect. [[Lorazepam]] is most commonly used but [[clonazepam]] is sometimes prescribed for acute psychosis or mania;<ref>{{cite journal | vauthors = Curtin F, Schulz P | title = Clonazepam and lorazepam in acute mania: a Bayesian meta-analysis | journal = Journal of Affective Disorders | volume = 78 | issue = 3 | pages = 201–208 | date = March 2004 | pmid = 15013244 | doi = 10.1016/S0165-0327(02)00317-8 }}</ref> their long-term use is not recommended due to risks of dependence.<ref name="BNF_2009"/>{{rp|204|date=November 2012}} Further research investigating the use of benzodiazepines alone and in combination with antipsychotic medications for treating acute psychosis is warranted.<ref>{{cite journal | vauthors = Gillies D, Sampson S, Beck A, Rathbone J | title = Benzodiazepines for psychosis-induced aggression or agitation | journal = Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD003079 | date = April 2013 | pmid = 23633309 | doi = 10.1002/14651858.CD003079.pub3 | hdl = 10454/16512 | hdl-access = free }}</ref>
* [[Clonazepam]], a benzodiazepine is used to treat many forms of [[parasomnia]].<ref>{{cite journal | vauthors = Schenck CH, Arnulf I, Mahowald MW | title = Sleep and sex: what can go wrong? A review of the literature on sleep related disorders and abnormal sexual behaviors and experiences | journal = Sleep | volume = 30 | issue = 6 | pages = 683–702 | date = June 2007 | pmid = 17580590 | pmc = 1978350 | doi = 10.1093/sleep/30.6.683}}</ref> [[Rapid eye movement behavior disorder]] responds well to low doses of clonazepam.<ref name="pmid10996567">{{cite journal | vauthors = Ferini-Strambi L, Zucconi M | title = REM sleep behavior disorder | journal = Clinical Neurophysiology | volume = 111 | issue = Suppl 2 | pages = S136–140 | date = September 2000 | pmid = 10996567 | doi = 10.1016/S1388-2457(00)00414-4 | s2cid = 43692512 }}</ref><ref>{{cite journal | vauthors = Silber MH | title = Sleep disorders | journal = Neurologic Clinics | volume = 19 | issue = 1 | pages = 173–186 | date = February 2001 | pmid = 11471763 | doi = 10.1016/S0733-8619(05)70011-6 }}</ref> [[Restless legs syndrome]] can be treated using clonazepam as a third line treatment option as the use of clonazepam is still investigational.<ref>{{cite journal | author = Grupo Brasileiro de Estudos em Síndrome das Pernas Inquietas (GBE-SPI) | title = Síndrome das pernas inquietas: diagnóstico e tratamento. Opinião de especialistas brasileiros | trans-title = Restless legs syndrome: diagnosis and treatment. Opinion of Brazilian experts | language = pt | journal = Arquivos de Neuro-Psiquiatria | volume = 65 | issue = 3A | pages = 721–727 | date = September 2007 | pmid = 17876423 | doi = 10.1590/S0004-282X2007000400035 | doi-access = free | title-link = doi | hdl = 11449/69841 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Trenkwalder C, Hening WA, Montagna P, Oertel WH, Allen RP, Walters AS, Costa J, Stiasny-Kolster K, Sampaio C | title = Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice | journal = Movement Disorders | volume = 23 | issue = 16 | pages = 2267–2302 | date = December 2008 | pmid = 18925578 | doi = 10.1002/mds.22254 | s2cid = 91440 | url = http://www.movementdisorders.org/publications/ebm_reviews/treatmentofrls.pdf | access-date = 19 January 2010 | archive-url = https://web.archive.org/web/20091229102940/http://www.movementdisorders.org/publications/ebm_reviews/treatmentofrls.pdf | archive-date = 29 December 2009 | url-status=dead }}</ref>
* Benzodiazepines are sometimes used for [[obsessive–compulsive disorder]] (OCD), although they are generally believed ineffective for this indication. Effectiveness was, however, found in one small study.<ref>{{cite book | title = The American Psychiatric Publishing Textbook of Psychopharmacology | date = 2009 | edition = Fourth | publisher = American Psychiatric Publishing | url = https://books.google.com/books?id=Xx7iNGdV25IC&pg=PA470 | isbn = 978-1-58562-309-9 | page = 470 | veditors = Schatzberg AF, Nemeroff CB }}</ref> Benzodiazepines can be considered as a treatment option in treatment resistant cases.<ref>{{cite journal | vauthors = Bandelow B | title = The medical treatment of obsessive-compulsive disorder and anxiety | journal = CNS Spectrums | volume = 13 | issue = 9 Suppl 14 | pages = 37–46 | date = September 2008 | pmid = 18849910 | doi = 10.1017/S1092852900026924 | s2cid = 26691595 }}</ref>
* [[Antipsychotics]] are generally a first-line treatment for delirium; however, when [[delirium]] is caused by alcohol or sedative hypnotic [[Drug withdrawal|withdrawal]], benzodiazepines are a first-line treatment.<ref name="Attard-2008">{{cite journal | vauthors = Attard A, Ranjith G, Taylor D | title = Delirium and its treatment | journal = CNS Drugs | volume = 22 | issue = 8 | pages = 631–644 | date = August 2008 | pmid = 18601302 | doi = 10.2165/00023210-200822080-00002 | s2cid = 94743 }}</ref>
* There is some evidence that low doses of benzodiazepines reduce adverse effects of [[electroconvulsive therapy]].<ref name="pmid22531198">{{cite journal | vauthors = Gallegos J, Vaidya P, D'Agati D, Jayaram G, Nguyen T, Tripathi A, Trivedi JK, Reti IM | title = Decreasing adverse outcomes of unmodified electroconvulsive therapy: suggestions and possibilities | journal = The Journal of ECT | volume = 28 | issue = 2 | pages = 77–81 | date = June 2012 | pmid = 22531198 | doi = 10.1097/YCT.0b013e3182359314 | s2cid = 6423840 }}</ref>