Editing Benzodiazepine (section)

===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/>