# Zolpidem > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Zolpidem > Markdown URL: https://mediated.wiki/source/Zolpidem.md > Source: https://en.wikipedia.org/wiki/Zolpidem > Source revision: 1355992328 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Sleep medication}} {{Use dmy dates|date=September 2024}} {{CS1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 418554530 | image = Zolpidem2DACS.svg | image_class = skin-invert-image | width = | alt = | image2 = Zolpidem ball-and-stick model.png | image_class2 = bg-transparent | width2 = | alt2 = | caption = | pronounce = | tradename = Ambien, others | Drugs.com = {{drugs.com|monograph|zolpidem-tartrate}} | MedlinePlus = a693025 | DailyMedID = Zolpidem | pregnancy_AU = B3 | pregnancy_AU_comment = {{cite web | title=Zolpidem Use During Pregnancy | website=Drugs.com | date=30 June 2020 | url=https://www.drugs.com/pregnancy/zolpidem.html | access-date=14 August 2020 | archive-date=20 June 2020 | archive-url=https://web.archive.org/web/20200620053822/https://www.drugs.com/pregnancy/zolpidem.html | url-status=live }} | pregnancy_category = | dependency_liability = [Physical](/source/Physical_dependence): High [Psychological](/source/Psychological_dependence): Moderate{{cite book| vauthors = Ries RK |title= Principles of addiction medicine|date=2009|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-7477-2|page=106|edition=4|url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PA106|url-status=live|archive-url=https://web.archive.org/web/20170908135444/https://books.google.com/books?id=j6GGBud8DXcC&pg=PA106|archive-date=8 September 2017}} | addiction_liability = High | routes_of_administration = [By mouth](/source/Oral_administration), [sublingual](/source/Sublingual_administration), oromucosal (spray), [rectal](/source/Rectal_administration) | class = [Nonbenzodiazepine](/source/Nonbenzodiazepine), [sedative-hypnotic](/source/sedative-hypnotic) | ATCvet = | ATC_prefix = N05 | ATC_suffix = CF02 | ATC_supplemental = | legal_AU = S4 | legal_AU_comment = {{cite web | title=Scheduling of zolpidem (Stilnox) | website=[Therapeutic Goods Administration](/source/Therapeutic_Goods_Administration) (TGA) | date=21 February 2008 | url=https://www.tga.gov.au/scheduling-zolpidem-stilnox | access-date=15 August 2020 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805143137/https://www.tga.gov.au/scheduling-zolpidem-stilnox | url-status=live }} | legal_BR = B1 | legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=3 August 2023 |publisher=[Diário Oficial da União](/source/Di%C3%A1rio_Oficial_da_Uni%C3%A3o) |language=pt-BR |publication-date=4 April 2023}} | legal_CA = Schedule IV | legal_CA_comment = | legal_DE = Rx-only/Anlage III | legal_DE_comment = | legal_NZ = Class C5 -rarely prescribed | legal_UK = Class C | legal_UK_comment = | legal_US = Schedule IV | legal_US_comment = {{cite web | title=Ambien- zolpidem tartrate tablet, film coated | website=DailyMed | date=29 August 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c36cadf4-65a4-4466-b409-c82020b42452 | access-date=15 August 2020 | archive-date=12 August 2020 | archive-url=https://web.archive.org/web/20200812034554/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c36cadf4-65a4-4466-b409-c82020b42452 | url-status=live }} | legal_EU = | legal_EU_comment = | legal_UN = Psychotropic Schedule IV | legal_UN_comment = | legal_status = Rx-only | bioavailability = 70% (by mouth) | protein_bound = 92% | metabolism = [Liver](/source/Liver) through [CYP3A4](/source/CYP3A4) (~60%), [CYP2C9](/source/CYP2C9) (~20%), and [CYP1A2](/source/CYP1A2) (~14%){{cite journal | vauthors = Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K, Harmatz JS, Shader RI | title = Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations | journal = British Journal of Clinical Pharmacology | volume = 48 | issue = 1 | pages = 89–97 | date = July 1999 | pmid = 10383565 | doi = 10.1046/j.1365-2125.1999.00953.x | pmc = 2014868 }} | metabolites = (ZCA) zolpidem 6-carboxylic acid; (ZPCA) zolpidem phenyl-4-carboxylic acid | onset = 15 minutes (oral spray)
30 minutes (oral tablets){{cite journal | vauthors = Neubauer D | title = ZolpiMistTM: a new formulation of zolpidem tartrate for the short-term treatment of insomnia in the US | journal = Nature and Science of Sleep | volume = 2 | pages = 79–84 | date = 10 May 2010 | pmid = 23616700 | pmc = 3630936 | doi = 10.2147/nss.s6431 | publisher = Dovepress | doi-access = free }} | elimination_half-life = 2–3 hours{{cite journal | vauthors = Salvà P, Costa J | title = Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications | journal = Clinical Pharmacokinetics | volume = 29 | issue = 3 | pages = 142–153 | date = September 1995 | pmid = 8521677 | doi = 10.2165/00003088-199529030-00002 | s2cid = 23391285 }} | duration_of_action = {{citation needed span|date=November 2025|3 hours (immediate release) }}
3–6 hours ([extended release](/source/Modified-release_dosage)) (duration & elimination varies by gender & age){{cite journal | vauthors = Bouchette D, Akhondi H, Patel P, Quick J | title = Zolpidem | journal = StatPearls | date = 29 February 2024 | url = https://www.ncbi.nlm.nih.gov/books/NBK442008/ | publisher = StatPearls Publishing | quote=for faster sleep onset, zolpidem tartrate tablets should not be ingested with or immediately after a meal. The controlled-release formulation maintains plasma levels for over 3 hours post-administration.}}{{cite journal | vauthors = Monti JM, Spence DW, Buttoo K, Pandi-Perumal SR | title = Zolpidem's use for insomnia | journal = Asian Journal of Psychiatry | volume = 25 | pages = 79–90 | date = February 2017 | pmid = 28262178 | doi = 10.1016/j.ajp.2016.10.006 | publisher = [Elsevier](/source/Elsevier) Inc. |quote=The duration of action of sublingual zolpidem-LD at the available dosages of 3.5 mg and 1.75 mg is approximately 4 h for patients who experience middle-of-the-night (MOTN) awakenings. A similar duration of action is observed following the administration of sublingual zolpidem-SD at the available dosages of 10 and 5 mg for the treatment of sleep-onset insomnia. Rebound insomnia as well as next-day hangover effects have been observed with zolpidem, but these symptoms are usually of short duration. | type = secondary source}}{{cite journal | vauthors = Kirkwood C, Neill J, Breden E | title = Zolpidem modified-release in insomnia. | journal = Neuropsychiatric Disease and Treatment | volume = 3 | issue = 5 | pages = 521–526 | date = 2007 | pmid = 19300582 | pmc = 2656288 | publisher = Dovepress | quote=The tmax of zolpidem MR (2.0 hours) was significantly longer than immediate-release zolpidem (2.4 hours) (p < 0.004). Pharmacodynamically, zolpidem MR potentiates sleep maintenance for greater than 3 hours and up to 6 hours compared with placebo in patients with primary insomnia. | type = Secondary source}} | excretion = [Kidney](/source/Kidney) (56%)
[fecal](/source/Feces) (34%){{cite journal | vauthors = Yaripour S, Mohammadi A, Esfanjani I, Walker R, Nojavan S | title = Quantitation of zolpidem in biological fluids by electro-driven microextraction combined with HPLC-UV analysis. | journal = EXCLI Journal | location = Tehran, Iran | volume = 17 | pages = 349–361 | date = 23 April 2018 | pmid = 29805344 | pmc = 5962899 | doi = 10.17179/excli2018-1140 | veditors = Mohammadi A | publisher = Tehran University of Medical Sciences | issn = 1611-2156 }} | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 82626-48-0 | PubChem = 5732 | IUPHAR_ligand = 4362 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00425 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5530 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 7K383OQI23 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08690 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 10125 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 911 | NIAID_ChemDB = | PDB_ligand = | synonyms = | IUPAC_name = ''N'',''N''-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide hemitartrate | C = 19 | H = 21 | N = 3 | O = 1 | SMILES = CN(C)C(=O)Cc1c(nc2ccc(C)cn12)c3ccc(C)cc3 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C19H21N3O/c1-13-5-8-15(9-6-13)19-16(11-18(23)21(3)4)22-12-14(2)7-10-17(22)20-19/h5-10,12H,11H2,1-4H3 | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = ZAFYATHCZYHLPB-UHFFFAOYSA-N | density = | density_notes = | melting_point = 193-197 | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }} '''Zolpidem''', sold under the brand name '''Ambien''' among others, is a [medication](/source/medication) primarily used for the short-term treatment of [sleeping problems](/source/sleeping_problems).{{cite web|title=Zolpidem (Monograph)|url=https://www.drugs.com/monograph/zolpidem-tartrate.html|publisher=The American Society of Health-System Pharmacists|date=27 April 2023|access-date=10 March 2024|archive-date=16 March 2018|archive-url=https://web.archive.org/web/20180316023759/https://www.drugs.com/monograph/zolpidem-tartrate.html|url-status=live}} Guidelines recommend that it be used only after [cognitive behavioral therapy for insomnia](/source/cognitive_behavioral_therapy_for_insomnia) and after behavioral changes, such as [sleep hygiene](/source/sleep_hygiene), have been tried. It decreases the time to [sleep onset](/source/sleep_onset) by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken [by mouth](/source/Oral_administration) and is available as conventional tablets, [extended-release tablets](/source/Modified-release_dosage), or [sublingual tablet](/source/sublingual_tablet)s. Common side effects include daytime [sleepiness](/source/sleepiness), headache, nausea, and diarrhea. More severe side effects include [memory problems](/source/memory_problems) and [hallucination](/source/hallucination)s.{{cite journal | vauthors = Matheson E, Hainer BL | title = Insomnia: Pharmacologic Therapy | journal = American Family Physician | volume = 96 | issue = 1 | pages = 29–35 | date = July 2017 | pmid = 28671376 | url = https://www.aafp.org/afp/2017/0701/p29.html | access-date = 18 August 2018 | archive-date = 19 August 2018 | archive-url = https://web.archive.org/web/20180819051215/https://www.aafp.org/afp/2017/0701/p29.html | url-status = live }} While [flumazenil](/source/flumazenil), a [GABAA receptor](/source/GABAA-rho_receptor) [antagonist](/source/receptor_antagonist), can reverse zolpidem's effects, usually [supportive care](/source/supportive_care) is all that is recommended in overdose.{{cite journal | vauthors = Gunja N | title = The clinical and forensic toxicology of Z-drugs | journal = Journal of Medical Toxicology | volume = 9 | issue = 2 | pages = 155–62 | date = June 2013 | pmid = 23404347 | pmc = 3657020 | doi = 10.1007/s13181-013-0292-0 }} Zolpidem is a [nonbenzodiazepine](/source/nonbenzodiazepine), or [Z-drug](/source/Z-drug), which acts as a [sedative](/source/sedative) and [hypnotic](/source/hypnotic) as a positive allosteric modulator at the GABAA receptor. It is an [imidazopyridine](/source/imidazopyridine) and increases [GABA](/source/GABA) effects in the [central nervous system](/source/central_nervous_system) by binding to GABAA receptors at the same location as [benzodiazepine](/source/benzodiazepine)s. It generally has a [half-life](/source/Elimination_half-life) of two to three hours. This, however, is increased in those with [liver problems](/source/liver_problems). Zolpidem was approved for medical use in the United States in 1992.{{cite web | title=Drug Approval Package: Ambien (Zolpidem Tartrate) NDA 19908 | website=U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/019908_S000_AmbienTOC.cfm | access-date=15 August 2020}} It became available as a [generic medication](/source/generic_medication) in 2007.{{cite press release | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108897.htm | archive-url = https://web.archive.org/web/20100306171628/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108897.htm | archive-date = 6 March 2010 | title = FDA Approves First Generic Versions of Ambien (Zolpidem Tartrate) for the Treatment of Insomnia | website = U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) | access-date = 24 January 2010}} Zolpidem is a [schedule IV](/source/Controlled_Substances_Act) controlled substance in the US under the [Controlled Substances Act of 1970](/source/Controlled_Substances_Act_of_1970) (CSA).{{cite web | title=Drug Scheduling | website=U.S. [Drug Enforcement Administration](/source/Drug_Enforcement_Administration) (DEA) | url=https://www.dea.gov/drug-information/drug-scheduling | access-date=24 December 2024 | archive-date=8 April 2024 | archive-url=https://web.archive.org/web/20240408102758/https://www.dea.gov/drug-information/drug-scheduling | url-status=live }} In 2023, it was the 54th most commonly prescribed medication in the United States, with more than 11{{nbsp}}million prescriptions.{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title = Zolpidem Drug Usage Statistics, United States, 2014–2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Zolpidem | access-date = 17 August 2025 }} ==Medical uses== [[Image:Kc-zolpidem-10mg.jpg|thumb|[Generic](/source/Generic_drug) zolpidem tartrate]] Zolpidem is labeled for short-term (usually about two to six weeks) treatment of [insomnia](/source/insomnia) at the lowest possible dose. It may be used for both improving [sleep onset](/source/sleep_onset), [sleep onset latency](/source/sleep_onset_latency), and staying asleep. Guidelines from [NICE](/source/NICE), the European Sleep Research Society, and the [American College of Physicians](/source/American_College_of_Physicians) recommend medication for insomnia (including possible zolpidem) only as a second-line treatment after non-pharmacological treatment options have been tried (e.g. [cognitive behavioral therapy for insomnia](/source/cognitive_behavioral_therapy_for_insomnia)).{{cite journal | vauthors = Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD | title = Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians | journal = Annals of Internal Medicine | volume = 165 | issue = 2 | pages = 125–33 | date = July 2016 | pmid = 27136449 | doi = 10.7326/M15-2175 | doi-access = free | title-link = doi }} This is based in part on a 2012 review which found that Zolpidem's effectiveness is nearly as much due to psychological effects as to the medication itself.{{cite journal | vauthors = Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN | title = Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration | journal = BMJ | volume = 345 | article-number = e8343 | date = December 2012 | pmid = 23248080 | pmc = 3544552 | doi = 10.1136/bmj.e8343 }} {{cs1 config|name-list-style=vanc|display-authors=6}} Increasingly, Zolpidem is being used [off-label](/source/Off-label_use) for the treatment of [comatose](/source/Coma) or [vegetative states](/source/Vegetative_state) for [brain injuries](/source/Brain_injury) originating outside of the [brain stem](/source/Brainstem). {{cite journal | vauthors = Du B, Shan A, Zhang Y, Zhong X, Chen D, Cai K | date = March 2014 | title = Zolpidem arouses patients in vegetative state after brain injury: quantitative evaluation and indications | journal = The American Journal of the Medical Sciences | volume = 347 | issue = 3 | pages = 178–182 | doi = 10.1097/MAJ.0b013e318287c79c | pmid = 23462249 }} Additionally, it has been implicated in the treatment of [aphasia](/source/aphasia) after [hypoxic stroke](/source/Stroke). While the full mechanism is currently unknown, [GABA](/source/GABA) stimulation appears to create [paradoxical excitement](/source/Paradoxical_reaction) in the brain, leading to a gradual recovery of cognitive, speech, and motor function. {{cite news | vauthors = Interlandi J | date = 2011-12-01 | title = A Drug That Wakes the Near Dead | language = en-US | work = The New York Times | url = https://www.nytimes.com/2011/12/04/magazine/can-ambien-wake-minimally-conscious.html | access-date = 2026-04-09 | issn = 0362-4331 }} As of 2026, the usage of Zolipdem for this purpose is scattered but has gradually increased since the breakthrough study published in 2007.{{cite journal | vauthors = Arnts H, van Erp WS, Boon LI, Bosman CA, Admiraal MM, Schrantee A, Pennartz CM, Schuurman R, Stam CJ, van Rootselaar AF, Hillebrand A, van den Munckhof P | date = November 2020 | title = Awakening after a sleeping pill: Restoring functional brain networks after severe brain injury | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 132 | pages = 135–146 | doi = 10.1016/j.cortex.2020.08.011 | pmid = 32979847 | hdl = 2066/228405 | hdl-access = free }} ==Contraindications== Use of zolpidem may impair driving skills with a resultant increased risk of [road traffic accidents](/source/road_traffic_accidents). This adverse effect is not unique to zolpidem but also occurs with other [hypnotic](/source/hypnotic) drugs. Caution should be exercised by motor vehicle drivers. The U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) recommends lower doses of zolpidem due to impaired function the day after taking it.{{cite web | title=Questions and Answers: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist) | website=U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) | date=13 February 2018 | url=https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-risk-next-morning-impairment-after-use-insomnia-drugs-fda-requires-lower | access-date=1 September 2024 | archive-date=1 September 2024 | archive-url=https://web.archive.org/web/20240901181043/https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-risk-next-morning-impairment-after-use-insomnia-drugs-fda-requires-lower }}{{cite web | title=FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR | website=U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) | date=11 December 2017 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-approves-new-label-changes-and-dosing-zolpidem-products-and | access-date=1 September 2024 | archive-date=27 September 2024 | archive-url=https://web.archive.org/web/20240927071102/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-approves-new-label-changes-and-dosing-zolpidem-products-and | url-status=live }}{{cite web | title = FDA Drug Safety Communication: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist) | date = 10 January 2013 | publisher = U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) | url = https://www.fda.gov/drugs/drugsafety/ucm334033.htm | access-date = 14 April 2013 | archive-date = 22 July 2017 | archive-url = https://web.archive.org/web/20170722033335/https://www.fda.gov/Drugs/DrugSafety/ucm334033.htm }}{{cite journal | vauthors = Norman JL, Fixen DR, Saseen JJ, Saba LM, Linnebur SA | title = Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes | journal = SAGE Open Medicine | volume = 5 | issue = | article-number = 2050312117707687 | date = 2017 | pmid = 28515934 | pmc = 5423710 | doi = 10.1177/2050312117707687 }} Zolpidem should not be prescribed to older people, who are more sensitive to the effects of hypnotics including zolpidem, and are at an increased risk of falls and adverse cognitive effects, such as [delirium](/source/delirium) and [neurocognitive disorder](/source/neurocognitive_disorder).{{cite journal | vauthors = Merel SE, Paauw DS | title = Common Drug Side Effects and Drug-Drug Interactions in Elderly Adults in Primary Care | journal = Journal of the American Geriatrics Society | volume = 65 | issue = 7 | pages = 1578–1585 | date = July 2017 | pmid = 28326532 | doi = 10.1111/jgs.14870 | s2cid = 6621392 }}{{cite journal | title = American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults | journal = Journal of the American Geriatrics Society | volume = 63 | issue = 11 | pages = 2227–46 | date = November 2015 | pmid = 26446832 | doi = 10.1111/jgs.13702 | url = https://www.sigot.org/allegato_docs/1057_Beers-Criteria.pdf | s2cid = 38797655 | vauthors = ((By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel)) | access-date = 29 June 2018 | archive-date = 16 May 2018 | archive-url = https://web.archive.org/web/20180516220158/http://www.sigot.org/allegato_docs/1057_Beers-Criteria.pdf | url-status = live }} Animal studies have revealed evidence of incomplete [ossification](/source/ossification) and increased [intrauterine fetal death](/source/intrauterine_fetal_death) at doses greater than seven times the maximum recommended human dose or higher; however, [teratogenicity](/source/teratogenicity) was not observed at any dose level. There are no controlled data on human pregnancy. In one case report, zolpidem was found in [cord blood](/source/cord_blood) at delivery. Zolpidem is recommended for use during pregnancy only when the benefits outweigh the risks.{{cite web | author = Drugsdb.eu | title = Zolpidem Pregnancy Warnings | url = http://drugsdb.eu/drug.php?d=Zolpidem&m=West-ward%20Pharmaceutical%20Corp&id=44d3d32b-6e68-4915-920e-ede52ed92f26.xml | access-date = 1 February 2014 | archive-date = 18 August 2018 | archive-url = https://web.archive.org/web/20180818115124/http://drugsdb.eu/drug.php?d=Zolpidem&m=West-ward }} ==Adverse effects== thumb|upright|Various zolpidem pills The most common adverse effects of short-term use include headache (reported by 7% of people in clinical trials), drowsiness (2%), dizziness (1%), and diarrhea (1%); the most common side effects of long-term use included drowsiness (8%), dizziness (5%), allergy (4%), sinusitis (4%), back pain (3%), diarrhea (3%), drugged feeling (3%), dry mouth (3%), lethargy (3%), sore throat (3%), abdominal pain (2%), constipation (2%), heart palpitations (2%), lightheadedness (2%), rash (2%), abnormal dreams (1%), amnesia (1%), chest pain (1%), depression (1%), flu-like symptoms (1%), and sleep disorder (1%). Zolpidem increases the risk of [depression](/source/Depression_(mood)), falls and bone fracture, poor driving, suppressed respiration and has been associated with an increased risk of death.{{cite journal | vauthors = Kripke DF | title = Mortality Risk of Hypnotics: Strengths and Limits of Evidence | journal = Drug Safety | volume = 39 | issue = 2 | pages = 93–107 | date = February 2016 | pmid = 26563222 | doi = 10.1007/s40264-015-0362-0 | url = https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t=nz1gjv | s2cid = 7946506 | doi-access = free | title-link = doi | access-date = 2 September 2019 | archive-date = 14 March 2020 | archive-url = https://web.archive.org/web/20200314025805/https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t=nz1gjv | url-status = live }} Upper and lower respiratory infections are also common (experienced by 1–10% of people). Residual 'hangover' effects, such as sleepiness and [impaired psychomotor](/source/Psychomotor_impairment) and [cognitive function](/source/Cognitive_Impairment), may persist into the day following nighttime administration. Such effects may impair the ability of users to drive safely and increase risks of falls and hip fractures.{{cite journal | vauthors = Vermeeren A | title = Residual effects of hypnotics: epidemiology and clinical implications | journal = CNS Drugs | volume = 18 | issue = 5 | pages = 297–328 | year = 2004 | pmid = 15089115 | doi = 10.2165/00023210-200418050-00003 | s2cid = 25592318 }} In January 2013, the FDA issued a safety communication addressing next-morning cognitive impairment associated with the drug. In May 2013, the FDA recommended avoiding activities requiring alertness the day after using extended-release formulations. ===Sleepwalking and complex sleep behaviors=== Zolpidem is associated with complex sleep behaviors (CSBs), defined as activities performed during sleep followed by amnesia. These activities may include [walking](/source/sleepwalking), driving, [eating](/source/night_eating_syndrome), having sex, having conversations, and performing other daily activities while asleep.{{cite journal |vauthors=Mittal N, Mittal R, Gupta MC |title=Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors |journal=Indian Journal of Psychological Medicine |volume=43 |issue=5 |pages=373–381 |date=September 2021 |pmid=34584301 |pmc=8450729 |doi=10.1177/0253717621992372}}{{cite web |title=Boxed Warning for risk of serious injuries caused by sleepwalking |website=U.S. Food and Drug Administration |date=30 April 2019 |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia |access-date=26 December 2024 |archive-date=2 May 2019 |archive-url=https://web.archive.org/web/20190502051204/https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia }} Research by Australia's [National Prescribing Service](/source/National_Prescribing_Service) found these activities typically occur after the first dose or within a few days of starting therapy,{{cite journal |journal=NPS Position Statement |title=Zolpidem and sleep-related behaviours |date=July 2008 |publisher=National Prescribing Service Limited |url=http://www.nps.org.au/__data/assets/pdf_file/0011/59888/Zolpidem_position_statement_To_print.pdf |archive-url=https://web.archive.org/web/20120410030254/http://www.nps.org.au/__data/assets/pdf_file/0011/59888/Zolpidem_position_statement_To_print.pdf |archive-date=10 April 2012}} although they may occur at any time during treatment. Concerns regarding zolpidem-related CSBs have prompted actions by regulatory authorities, including Australia's [Therapeutic Goods Administration](/source/Therapeutic_Goods_Administration) (TGA) and the U.S. Food and Drug Administration (FDA). In February 2008, the TGA implemented a [boxed warning](/source/boxed_warning) for the drug.{{cite web | url = https://www.tga.gov.au/alerts/stilnox2.htm | archive-url = https://web.archive.org/web/20090603203455/https://www.tga.gov.au/alerts/stilnox2.htm | archive-date = 3 June 2009 | title = Zolpidem ('Stilnox') – updated information – February 2008 | publisher = [Therapeutic Goods Administration](/source/Therapeutic_Goods_Administration) (TGA) | access-date = 22 June 2009 | date=21 February 2008 }} In April 2019, the FDA strengthened the drug's warning labeling by adding a black box warning highlighting the risk of serious injuries and fatalities related to CSBs, even at recommended doses and after single use, and added a contraindication advising against zolpidem use in patients with a history of CSBs. ===Tolerance, dependence and withdrawal=== thumb|Ambien tablets As zolpidem is associated with [drug tolerance](/source/drug_tolerance) and [substance dependence](/source/substance_dependence), its [prescription guidelines](/source/medication_package_insert) are only for severe insomnia and short periods of use at the lowest effective dose.{{cite web |title=Stilnoct 10mg Film-Coated Tablets - Summary of Product Characteristics (SmPC) |url=https://www.medicines.org.uk/emc/product/4933/smpc |publisher=UK Electronic Medicines Compendium |access-date=19 August 2018 |date=21 May 2018 |archive-date=20 August 2018 |archive-url=https://web.archive.org/web/20180820005704/https://www.medicines.org.uk/emc/product/4933/smpc }}{{cite web |title=Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia |url=https://www.nice.org.uk/guidance/ta77/chapter/1-Guidance |publisher=NICE |date=28 April 2004 |access-date=19 August 2018 |archive-date=20 August 2018 |archive-url=https://web.archive.org/web/20180820005722/https://www.nice.org.uk/guidance/ta77/chapter/1-Guidance |url-status=live }}{{cite journal | vauthors = Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Gonçalves M, Hertenstein E, Jansson-Fröjmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weeß HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K | title = European guideline for the diagnosis and treatment of insomnia | journal = Journal of Sleep Research | volume = 26 | issue = 6 | pages = 675–700 | date = December 2017 | pmid = 28875581 | doi = 10.1111/jsr.12594 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M | title = Clinical guideline for the evaluation and management of chronic insomnia in adults | journal = Journal of Clinical Sleep Medicine | volume = 4 | issue = 5 | pages = 487–504 | date = October 2008 | pmid = 18853708 | pmc = 2576317 | doi = 10.5664/jcsm.27286 }} Tolerance to the effects of zolpidem can develop in some people in just a few weeks. Abrupt withdrawal may cause [delirium](/source/delirium), seizures, or other [adverse effect](/source/adverse_effect)s, especially if used for prolonged periods and at high doses.{{cite journal | vauthors = Gunja N | title = In the Zzz zone: the effects of Z-drugs on human performance and driving | journal = Journal of Medical Toxicology | volume = 9 | issue = 2 | pages = 163–71 | date = June 2013 | pmid = 23456542 | pmc = 3657033 | doi = 10.1007/s13181-013-0294-y }}{{cite journal | vauthors = Janhsen K, Roser P, Hoffmann K | title = The problems of long-term treatment with benzodiazepines and related substances | journal = Deutsches Ärzteblatt International | volume = 112 | issue = 1–2 | pages = 1–7 | date = January 2015 | pmid = 25613443 | pmc = 4318457 | doi = 10.3238/arztebl.2015.0001 }} When drug tolerance and [physical dependence](/source/physical_dependency) to zolpidem develop, treatment usually entails a gradual dose reduction over a period of months to minimize [withdrawal symptom](/source/withdrawal_symptom)s, which can resemble those seen during [benzodiazepine withdrawal](/source/benzodiazepine_withdrawal_syndrome). Failing that, an alternative method may be necessary for some people, such as a switch to a [benzodiazepine equivalent](/source/benzodiazepine_equivalent) dose of a longer-acting benzodiazepine drug, as for [diazepam](/source/diazepam) or [chlordiazepoxide](/source/chlordiazepoxide), followed by a gradual reduction in dose of the long-acting [benzodiazepine](/source/benzodiazepine). In people who are difficult to treat, an [inpatient](/source/inpatient) [flumazenil](/source/flumazenil) administration allows for rapid [competitive binding](/source/competitive_binding) of flumazenil to GABAA–receptor as an [antagonist](/source/Antagonist_(drug)), thus stopping (and effectively [detoxifying](/source/detoxifying)) zolpidem from being able to bind as an [agonist](/source/agonist) on GABAA–receptor; slowly [drug dependence](/source/drug_dependence) or [addiction](/source/Substance_use_disorder) to zolpidem will wane.{{cite journal | vauthors = Quaglio G, Lugoboni F, Fornasiero A, Lechi A, Gerra G, Mezzelani P | title = Dependence on zolpidem: two case reports of detoxification with flumazenil infusion | journal = International Clinical Psychopharmacology | volume = 20 | issue = 5 | pages = 285–7 | date = September 2005 | pmid = 16096519 | doi = 10.1097/01.yic.0000166404.41850.b4 }} [Alcoholics or recovering alcoholics](/source/Alcoholism) may be at increased risk of physical dependency or abuse of zolpidem. It is not typically prescribed to people with a history of alcoholism, [recreational drug use](/source/drug_misuse), physical dependency, or [psychological dependency](/source/Substance_dependence) on sedative-hypnotic drugs. A 2014 review found evidence of [drug-seeking behavior](/source/drug-seeking_behavior), with prescriptions for zolpidem making up 20% of falsified or forged prescriptions.{{cite journal | vauthors = Victorri-Vigneau C, Gérardin M, Rousselet M, Guerlais M, Grall-Bronnec M, Jolliet P | title = An update on zolpidem abuse and dependence | journal = Journal of Addictive Diseases | volume = 33 | issue = 1 | pages = 15–23 | year = 2014 | pmid = 24467433 | doi = 10.1080/10550887.2014.882725 | s2cid = 30959471 }} [Rodent](/source/Rodent) studies of the [tolerance](/source/drug_tolerance)-inducing properties have shown that zolpidem has less tolerance-producing potential than benzodiazepines, but in [primate](/source/primate)s, the tolerance-producing potential of zolpidem was the same as seen with benzodiazepines.{{cite journal | vauthors = Petroski RE, Pomeroy JE, Das R, Bowman H, Yang W, Chen AP, Foster AC | title = Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 1 | pages = 369–77 | date = April 2006 | pmid = 16399882 | doi = 10.1124/jpet.105.096701 | s2cid = 46510829 }} Zolpidem misuse has been associated with dependence and addiction, often driven by its euphoric effects. Reported cases include extremely high daily doses, sometimes up to 6,000 mg, with withdrawal symptoms such as [seizure](/source/seizure)s, [tremor](/source/tremor)s, [delirium](/source/delirium), and [irritability](/source/irritability). Management typically involves tapering or substitution with long-acting benzodiazepines, occasionally with [flumazenil](/source/flumazenil) or [cholinesterase inhibitor](/source/cholinesterase_inhibitor)s, alongside [psychosocial](/source/psychosocial) therapies such as [mindfulness](/source/mindfulness)-based [cognitive therapy](/source/cognitive_therapy). While organ toxicity is rare, high doses can cause severe central nervous system effects.{{cite journal | vauthors = Xie F, Liu B, Yang L, Huang J, Li B, Li Y | title = Zolpidem-related euphoria, addiction and detoxification: A case report and review of the literature | journal = Medicine | volume = 103 | issue = 44 | date = November 2024 | pmid = 39496046 | doi = 10.1097/MD.0000000000040280 | article-number = e40280 | pmc = 11537603 }} ===Overdose=== Overdose can lead to coma or death. Zolpidem overdose can be treated with the [GABAA receptor antagonist](/source/GABA_receptor_antagonist) [flumazenil](/source/flumazenil), which displaces zolpidem from its [binding site](/source/binding_site) on the [GABAA receptor](/source/GABA_receptor) to rapidly reverse the effects of the zolpidem. ===Detection in body fluids=== Zolpidem may be quantitated in blood or plasma to confirm a diagnosis of poisoning in people who are hospitalized, to provide evidence in an impaired driving arrest, or to assist in a medicolegal death investigation. Blood or plasma zolpidem concentrations are usually in a range of 30–300{{nbsp}}μg/L in persons receiving the drug therapeutically, 100–700{{nbsp}}μg/L in those arrested for impaired driving, and 1000–7000{{nbsp}}μg/L in victims of acute overdosage. Analytical techniques, in general, involve [gas](/source/Gas_chromatography) or [liquid](/source/High-performance_liquid_chromatography) [chromatography](/source/chromatography).{{cite journal | vauthors = Gock SB, Wong SH, Nuwayhid N, Venuti SE, Kelley PD, Teggatz JR, Jentzen JM | title = Acute zolpidem overdose--report of two cases | journal = Journal of Analytical Toxicology | volume = 23 | issue = 6 | pages = 559–62 | date = October 1999 | pmid = 10517569 | doi = 10.1093/jat/23.6.559 | doi-access = free | title-link = doi }}{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 9th | publisher = Biomedical Publications | location = Seal Beach, CA | year = 2011 | pages = 1836–1838}} ==Pharmacology== {| class="wikitable floatright" style="font-size:small;" |+Binding profile{{cite web | title = PDSP Ki Database | work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | author1-link = Bryan Roth | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 23 August 2024 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=zolpidem&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query }} |- ! Site !! Ki (nM) |- | [GABAA Benzodiazepine Type I](/source/Benzodiazepine)c || 25 |- | [GABAA Benzodiazepine](/source/GABAA_receptor_positive_allosteric_modulator)b || 26 |- | {{abbrlink|GABAA α1|Gamma-aminobutyric acid receptor subunit alpha-1|}} || 27 |- | {{abbrlink|GABAA α1β1γ2|GABA A Alpha1 Beta1 Gamma2}} || 111.9 |- | {{abbrlink|GABAA α1β3γ2|GABA A Alpha1 Beta3 Gamma2}} || 41 |- | {{abbrlink|GABAA α2|Gamma-aminobutyric acid receptor subunit alpha-2}} || 160 |- | {{abbrlink|GABAA α2β1γ2|GABA A Alpha2Beta1Gamma2}} || 760.6 |- | {{abbrlink|GABAA α2β2γ2|GABA A Alpha2Beta2Gamma2}}a || 765 |- |{{abbrlink|GABAA α3|Gamma-aminobutyric acid receptor subunit alpha-3}} || 380 |- | {{abbrlink|GABAA α3β1γ2|GABA A Alpha3 Beta1 Gamma2}} || 2149.5 |- | {{abbrlink|GABAA α4β3γ2|GABA A Alpha4 Beta3 Gamma2}}|| > 10,000 |- | {{abbrlink|GABAA α5β1γ2|GABA A Alpha5 Beta1 Gamma2}}|| > 10,000 |- |{{abbrlink|GABAA α6β3γ2|GABA A Alpha6 Beta3 Gamma2}} || > 10,000 |- class="sortbottom" | colspan="5" style="width: 1px;" | Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. All values are for human receptors unless otherwise specified. a[HEK293](/source/HEK293) bRat's [cerebral cortex](/source/cerebral_cortex). cRat's [hippocampus](/source/hippocampus). Additional sources:{{cite book | vauthors = Herman JH, Sheldon SH | title=Principles and Practice of Pediatric Sleep Medicine | chapter=Pharmacology of Sleep Disorders in Children | publisher=Elsevier | date=2005 | isbn=978-0-7216-9458-0 | doi=10.1016/b978-0-7216-9458-0.50033-7 | pages=327–338 | quote=On [recombinant receptors](/source/recombinant_receptors), zolpidem displays a high affinity for only the α1-GABAA receptors and an intermediate affinity for α2- and α3-GABAA receptors. It does not bind to α5-GABAA receptors. The sedative action of zolpidem is exclusively mediated by α1-GABA receptors. }}{{cite journal | vauthors = Carling RW, Madin A, Guiblin A, Russell MG, Moore KW, Mitchinson A, Sohal B, Pike A, Cook SM, Ragan IC, McKernan RM, Quirk K, Ferris P, Marshall G, Thompson SA, Wafford KA, Dawson GR, Atack JR, Harrison T, Castro JL, Street LJ | title = 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 23 | pages = 7089–7092 | date = November 2005 | pmid = 16279764 | doi = 10.1021/jm058034a }} |} ===Mechanism of action=== frame|right Zolpidem is a [ligand](/source/Ligand_(biochemistry)) of high-affinity [positive modulator](/source/allosteric_modulator) sites of [GABAA receptors](/source/GABAA_receptor), which enhances [GABAergic](/source/GABAergic) inhibition of neurotransmission in the central nervous system. It selectively binds to [α1](/source/Gamma-aminobutyric_acid_receptor_subunit_alpha-1) [subunits](/source/Protein_subunit) of this [pentameric](/source/pentameric_protein) [ion channel](/source/Ligand-gated_ion_channel). Accordingly, it has strong [hypnotic](/source/hypnotic) properties and weak [anxiolytic](/source/anxiolytic), [myorelaxant](/source/myorelaxant), and [anticonvulsant](/source/anticonvulsant) properties. Opposed to [diazepam](/source/diazepam), zolpidem is able to bind to binary αβ [GABA receptor](/source/GABA_receptor)s, where it was shown to bind to the α1–α1 subunit interface.{{cite journal | vauthors = Che Has AT, Absalom N, van Nieuwenhuijzen PS, Clarkson AN, Ahring PK, Chebib M | title = Zolpidem is a potent stoichiometry-selective modulator of α1β3 GABAA receptors: evidence of a novel benzodiazepine site in the α1-α1 interface | journal = Scientific Reports | volume = 6 | article-number = 28674 | date = June 2016 | pmid = 27346730 | pmc = 4921915 | doi = 10.1038/srep28674 | bibcode = 2016NatSR...628674C }} Zolpidem has about 10-fold lower affinity for the [α2](/source/GABRA2)- and [α3](/source/GABRA3)- subunits than for α1, and no appreciable affinity for [α5](/source/GABRA5) subunit-containing receptors.{{cite journal | vauthors = Pritchett DB, Seeburg PH | title = Gamma-aminobutyric acidA receptor alpha 5-subunit creates novel type II benzodiazepine receptor pharmacology | journal = Journal of Neurochemistry | volume = 54 | issue = 5 | pages = 1802–4 | date = May 1990 | pmid = 2157817 | doi = 10.1111/j.1471-4159.1990.tb01237.x | s2cid = 86674799 }}{{cite journal | vauthors = Smith AJ, Alder L, Silk J, Adkins C, Fletcher AE, Scales T, Kerby J, Marshall G, Wafford KA, McKernan RM, Atack JR | title = Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux | journal = Molecular Pharmacology | volume = 59 | issue = 5 | pages = 1108–18 | date = May 2001 | pmid = 11306694 | doi = 10.1124/mol.59.5.1108| s2cid = 86156878 }} ω1 type GABAA receptors are the α1-containing GABAA receptors and are found primarily in the brain, the ω2 receptors are those that contain the α2-, α3-, [α4](/source/GABRA4)-, α5-, or [α6](/source/GABRA6) subunits, and are found primarily in the spine. Thus, zolpidem favours binding to GABAA receptors located in the brain rather than the spine.{{cite journal | vauthors = Rowlett JK, Woolverton WL | title = Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA2 and pKB analyses from behavioral studies | journal = Psychopharmacology | volume = 128 | issue = 1 | pages = 1–16 | date = November 1996 | pmid = 8944400 | doi = 10.1007/s002130050103 | s2cid = 25654504 | url = http://link.springer.de/link/service/journals/00213/bibs/6128001/61280001.htm | archive-url = https://web.archive.org/web/20020112111228/http://link.springer.de/link/service/journals/00213/bibs/6128001/61280001.htm | archive-date = 12 January 2002 | url-access = subscription }} Zolpidem has no affinity for γ1 and γ3 subunit-containing receptors and, like the vast majority of benzodiazepine-like drugs, it lacks affinity for receptors containing α4 and α6.{{cite journal | vauthors = Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ | title = Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit | journal = Molecular Pharmacology | volume = 50 | issue = 3 | pages = 670–8 | date = September 1996 | doi = 10.1016/S0026-895X(25)09339-3 | pmid = 8794909 | url = http://molpharm.aspetjournals.org/cgi/content/abstract/50/3/670 | access-date = 7 October 2007 | archive-date = 8 January 2009 | archive-url = https://web.archive.org/web/20090108105647/http://molpharm.aspetjournals.org/cgi/content/abstract/50/3/670 | url-access = subscription }} Zolpidem modulates the receptor presumably by inducing a receptor conformation that enables an increased binding strength of the [orthosteric](/source/Orthosteric_site) agonist GABA towards its cognate receptor without affecting [desensitization](/source/Downregulation_and_upregulation) or peak currents.{{cite journal | vauthors = Perrais D, Ropert N | title = Effect of zolpidem on miniature IPSCs and occupancy of postsynaptic GABAA receptors in central synapses | journal = The Journal of Neuroscience | volume = 19 | issue = 2 | pages = 578–88 | date = January 1999 | pmid = 9880578 | pmc = 6782193 | doi = 10.1523/JNEUROSCI.19-02-00578.1999}} Like [zaleplon](/source/zaleplon), zolpidem may increase [slow-wave sleep](/source/slow-wave_sleep) but cause no effect on stage 2 sleep.{{cite journal | vauthors = Noguchi H, Kitazumi K, Mori M, Shiba T | title = Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats | journal = Journal of Pharmacological Sciences | volume = 94 | issue = 3 | pages = 246–51 | date = March 2004 | pmid = 15037809 | doi = 10.1254/jphs.94.246 | doi-access = free | title-link = doi }} A 2004 [meta-analysis](/source/meta-analysis) compared benzodiazepines against [nonbenzodiazepine](/source/nonbenzodiazepine)s and showed few consistent differences between zolpidem and [benzodiazepine](/source/benzodiazepine)s in terms of [sleep onset latency](/source/sleep_onset_latency), total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, [rebound insomnia](/source/rebound_insomnia), and daytime alertness.{{cite journal | vauthors = Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T | title = Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis | journal = Human Psychopharmacology | volume = 19 | issue = 5 | pages = 305–22 | date = July 2004 | pmid = 15252823 | doi = 10.1002/hup.594 | s2cid = 10888200 }} === Pharmacokinetics === Microsome studies indicate zolpidem is metabolized by [CYP3A4](/source/CYP3A4) (61%) [CYP2C9](/source/CYP2C9) (22%), [CYP1A2](/source/CYP1A2) (14%), [CYP2D6](/source/CYP2D6) (<3%), and [CYP2C19](/source/CYP2C19) (<3%). Less than 1% is excreted in urine unchanged. It is principally metabolized into three metabolites, none of which are believed to be pharmacologically active. The absolute [bioavailability](/source/bioavailability) of zolpidem is about 70%. The drug reaches peak concentration in about 2 hours and has a half-life in healthy adults of about 2–3 hours.{{cite book | vauthors = Mendelson W | chapter=Hypnotic Medications | veditors = Kryger MH, Roth T, Dement WC | title=Principles and Practice of Sleep Medicine | edition = 5th | publisher=Elsevier | date=2011 | isbn=978-1-4160-6645-3 | doi=10.1016/b978-1-4160-6645-3.00042-6 | pages=483–491 }} Zolpidem's half life is decreased in children and increased in the elderly and people with liver issues. While some studies show men metabolize zolpidem faster than women (possibly due to [testosterone](/source/testosterone)),{{cite journal | vauthors = Olubodun JO, Ochs HR, von Moltke LL, Roubenoff R, Hesse LM, Harmatz JS, Shader RI, Greenblatt DJ | title = Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men | journal = British Journal of Clinical Pharmacology | volume = 56 | issue = 3 | pages = 297–304 | date = September 2003 | pmid = 12919178 | doi = 10.1046/j.0306-5251.2003.01852.x | pmc = 1884349 }} others do not. A review found only a 33% lower clearance in women compared to men, suggesting the FDA's dosage reduction of 50% for women may have been too large.{{cite journal | vauthors = Greenblatt DJ, Harmatz JS, Roth T | title = Zolpidem and Gender: Are Women Really At Risk? | journal = Journal of Clinical Psychopharmacology | volume = 39 | issue = 3 | pages = 189–199 | date = May 2019 | pmid = 30939589 | doi = 10.1097/JCP.0000000000001026 | s2cid = 92998845 }} ==Interactions== People should not consume [alcohol](/source/alcohol_(drug)) or use [opioid](/source/opioid)s while using Zolpidem.{{Cite web|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or|title=FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning|publisher=U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA)|date=31 August 2016|access-date=18 August 2018|archive-date=18 January 2024|archive-url=https://web.archive.org/web/20240118205732/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or|url-status=live}} Use of opioids with zolpidem increases the risk of respiratory depression and death. The U.S. Food and Drug Administration (FDA) is advising that the opioid addiction medications [buprenorphine](/source/buprenorphine) and [methadone](/source/methadone) should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system (CNS).{{cite web | title=FDA urges caution about withholding opioid addiction medications | website=U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA) | date=20 September 2017 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications | access-date=15 August 2020 | archive-date=12 May 2020 | archive-url=https://web.archive.org/web/20200512225421/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications | url-status=live }} {{PD-notice}} Next day sedation can be worsened if people take zolpidem while they are also taking [antipsychotic](/source/antipsychotic)s, other sedatives, anxiolytics, antidepressants, anticonvulsants, and antihistamines. Some people taking antidepressants have had visual hallucinations when they also took zolpidem. [Cytochrome P450](/source/Cytochrome_P450) inhibitors, particularly CYP3A4 and CYP1A2 inhibitors such as [fluvoxamine](/source/fluvoxamine), [ciprofloxacin](/source/ciprofloxacin), and [clarithromycin](/source/clarithromycin){{cite journal | vauthors = Lee CM, Jung EH, Byeon JY, Kim SH, Jang CG, Lee YJ, Lee SY | title = Effects of steady-state clarithromycin on the pharmacokinetics of zolpidem in healthy subjects | journal = Archives of Pharmacal Research | volume = 42 | issue = 12 | pages = 1101–1106 | date = December 2019 | pmid = 31820397 | doi = 10.1007/s12272-019-01201-5 | s2cid = 209164976 }} will increase the effects of a given dose of zolpidem. Cytochrome P450 activators like [St. John's Wort](/source/St._John's_Wort) may decrease the activity of zolpidem. One study found that caffeine increases the concentration over time curve of zolpidem by about 20% and furthermore found that caffeine cannot adequately compensate for the impaired cognition caused by zolpidem.{{cite journal | vauthors = Cysneiros RM, Farkas D, Harmatz JS, von Moltke LL, Greenblatt DJ | title = Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine | journal = Clinical Pharmacology and Therapeutics | volume = 82 | issue = 1 | pages = 54–62 | date = July 2007 | pmid = 17443132 | doi = 10.1038/sj.clpt.6100211 | s2cid = 46250744 }} Other studies show no effect of caffeine on zolpidem metabolism. ==Chemistry== Three [chemical syntheses](/source/chemical_synthesis) of zolpidem are common. [4-Methylacetophenone](/source/4-Methylacetophenone) is first brominated and that product is treated with 2-amino-5-methylpyridine to give the [imidazopyridine](/source/imidazopyridine). From here the reactions use a variety of reagents to complete the synthesis, either involving [thionyl chloride](/source/thionyl_chloride) or [sodium cyanide](/source/sodium_cyanide). These reagents are challenging to handle and require thorough safety assessments.{{cite book |vauthors=Johnson DS, Li JJ | title = The art of drug synthesis | year = 2007 | publisher = Wiley-Interscience | location = Hoboken, N.J. | isbn = 978-0-471-75215-8 | pages = Chapter 15, Section 2 }}{{Cite patent | inventor = Rawalnath SR, Crasta Santosh R, Saxena A | publication-date = 21 December 2005 | title = Process for the preparation of zolpidem | issue-date = 14 February 2011 | country-code = IN | patent-number = 246080 }}{{cite journal | vauthors = Sumalatha Y | title = A simple and efficient synthesis of hypnotic agent, zolpidem and its related substances | journal = Arkivoc | volume = 2009 | issue = 2 | pages = 315–320 | year = 2009 | doi = 10.3998/ark.5550190.0010.230 | doi-access = free | title-link = doi | hdl = 2027/spo.5550190.0010.230 | hdl-access = free }} Though such safety procedures are common in the industry, they make clandestine manufacture difficult. Several major side-products of the sodium cyanide reaction have been characterised and include dimers and mannich products.{{cite journal | vauthors = Sumalatha Y | title = Synthesis and spectral characterization of zolpidem related substances - hypnotic agent | journal = Arkivoc | volume = 2009 | issue = 7 | pages = 143–149 | year = 2009 | doi = 10.3998/ark.5550190.0010.714 | doi-access = free | title-link = doi | hdl = 2027/spo.5550190.0010.714 | hdl-access = free }} [Alpidem](/source/Alpidem) is also an imidazopyridine and is an [analogue](/source/structural_analog) of zolpidem.{{cite journal | vauthors = Langer SZ, Arbilla S, Benavides J, Scatton B | title = Zolpidem and alpidem: two imidazopyridines with selectivity for omega 1- and omega 3-receptor subtypes | journal = Adv Biochem Psychopharmacol | volume = 46 | issue = | pages = 61–72 | date = 1990 | pmid = 1981304 | doi = | url = }}{{cite journal | vauthors = Sanger DJ, Benavides J, Perrault G, Morel E, Cohen C, Joly D, Zivkovic B | title = Recent developments in the behavioral pharmacology of benzodiazepine (omega) receptors: evidence for the functional significance of receptor subtypes | journal = Neurosci Biobehav Rev | volume = 18 | issue = 3 | pages = 355–72 | date = 1994 | pmid = 7984354 | doi = 10.1016/0149-7634(94)90049-3 | s2cid = 11612995 | url = }}{{cite journal | vauthors = Skolnick P | title = Anxioselective anxiolytics: on a quest for the Holy Grail | journal = Trends Pharmacol Sci | volume = 33 | issue = 11 | pages = 611–20 | date = November 2012 | pmid = 22981367 | pmc = 3482271 | doi = 10.1016/j.tips.2012.08.003 | url = }} Both agents are GABAA receptor positive allosteric modulators. However, whereas zolpidem is used as a hypnotic and sedative, alpidem was used as an [anxiolytic](/source/anxiolytic). ==History== Zolpidem was used in Europe starting in 1988 and was brought to market there by [Synthelabo](/source/Synthelabo).{{cite news | vauthors = Morris S |title=Searle Wins Ok To Sell Sleep Aid |url=https://www.chicagotribune.com/1992/12/22/searle-wins-ok-to-sell-sleep-aid/ |work=Chicago Tribune |date=22 December 1992 }} Synthelabo and [Searle](/source/G.D._Searle%2C_LLC) collaborated to bring it to market in the US, and it was approved in the United States in 1992 under the brand name "Ambien". It became available as a [generic medication](/source/generic_medication) in 2007. In 2015, the [American Geriatrics Society](/source/American_Geriatrics_Society) said that zolpidem, [eszopiclone](/source/eszopiclone), and [zaleplon](/source/zaleplon) met the [Beers criteria](/source/Beers_criteria) and should be avoided in individuals 65 and over "because of their association with harms balanced with their minimal efficacy in treating insomnia." The AGS stated the strength of the recommendation that older adults avoid zolpidem is "strong" and the quality of evidence supporting it is "moderate." ==Society and culture== Prescriptions in the US for all sleeping pills (including zolpidem) steadily declined from around 57 million tablets in 2013, to around 47 million in 2017, possibly due to concern about prescribing addictive drugs amid the [opioid crisis](/source/opioid_crisis).{{cite news | vauthors = Crow D |title=Ambien defence: the real side effects of sleeping pills |url=https://www.ft.com/content/cca81c52-6518-11e8-a39d-4df188287fff |archive-url=https://ghostarchive.org/archive/20221210/https://www.ft.com/content/cca81c52-6518-11e8-a39d-4df188287fff |archive-date=10 December 2022 |url-status=live |work=Financial Times |date=1 June 2018 | url-access=subscription }} ===Military use=== As of 2012, the [United States Air Force](/source/United_States_Air_Force) used zolpidem as one of the hypnotics approved as a "[no-go pill](/source/no-go_pill)" with a six-hour restriction on subsequent flight operation to help aviators and special duty personnel sleep in support of mission readiness. (The other hypnotics used are [temazepam](/source/temazepam) and [zaleplon](/source/zaleplon).) "Ground tests" are required before an authorization is issued to use the medication in an operational situation.{{cite web|url=http://static.e-publishing.af.mil/production/1/afsoc/publication/afsoci48-101/afsoci48-101.pdf |title=Air Force Special Operations Command Instruction 48-101 |work=e-publishing.af.mil |date=30 November 2012|access-date=8 March 2014 |archive-url=https://web.archive.org/web/20140611124025/http://static.e-publishing.af.mil/production/1/afsoc/publication/afsoci48-101/afsoci48-101.pdf |archive-date=11 June 2014 }} ===Recreational use=== Zolpidem has potential for medical misuse when the drug is continued long term without or against medical advice, or for recreational use when the drug is taken to achieve a "[high](/source/Substance_intoxication)".{{cite journal | vauthors = Brett J, Murnion B | title = Management of benzodiazepine misuse and dependence | journal = Australian Prescriber | volume = 38 | issue = 5 | pages = 152–5 | date = October 2015 | pmid = 26648651 | pmc = 4657308 | doi = 10.18773/austprescr.2015.055 }}{{cite journal | vauthors = Griffiths RR, Johnson MW | title = Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds | journal = The Journal of Clinical Psychiatry | volume = 66 | issue = Suppl 9 | pages = 31–41 | year = 2005 | pmid = 16336040 }} The transition from medical use of zolpidem to high-dose addiction or [drug dependence](/source/drug_dependence) can occur with use, but some believe it may be more likely when used without a clinical recommendation to continue using it, when physiological [drug tolerance](/source/drug_tolerance) leads to higher doses than the usual 5{{nbsp}}mg or 10{{nbsp}}mg, when consumed through insufflation or injection, or when taken for purposes other than as a sleep aid. Recreational use is more prevalent in those having been dependent on other drugs in the past, but tolerance and [drug dependence](/source/drug_dependence) can still sometimes occur in those without a history of drug dependence. Chronic users of high doses are more likely to develop [physical dependence](/source/physical_dependence) on the drug, which may cause severe withdrawal symptoms, including seizures if abrupt withdrawal from zolpidem occurs.{{cite journal | vauthors = Barrero-Hernández FJ, Ruiz-Veguilla M, López-López MI, Casado-Torres A | title = [Epileptic seizures as a sign of abstinence from chronic consumption of zolpidem] | language = es | journal = Revista de Neurología | volume = 34 | issue = 3 | pages = 253–6 | year = 2002 | pmid = 12022074 | doi = 10.33588/rn.3403.2001316| trans-title = Epileptic seizures as a sign of abstinence from chronic consumption of zolpidem }} Other drugs, including benzodiazepines and [zopiclone](/source/zopiclone), are also found in high numbers of suspected drugged drivers. Many drivers have blood levels far exceeding the therapeutic dose range, suggesting a high degree of excessive-use potential for [benzodiazepine](/source/benzodiazepine)s, zolpidem, and zopiclone.{{cite journal | vauthors = Jones AW, Holmgren A, Kugelberg FC | title = Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results | journal = Therapeutic Drug Monitoring | volume = 29 | issue = 2 | pages = 248–60 | date = April 2007 | pmid = 17417081 | doi = 10.1097/FTD.0b013e31803d3c04 | s2cid = 25511804 }} U.S. Congressman [Patrick J. Kennedy](/source/Patrick_J._Kennedy) says that he was using zolpidem (Ambien) and [promethazine](/source/promethazine) (Phenergan) when he was caught driving erratically at 3 a.m.{{cite news | url = http://wcco.com/national/Rep.Patrick.Kennedy.2.267357.html | title = Kennedy To Enter Drug Rehab After Car Crash; Congressman Wrecked Car Near Capitol | access-date = 23 June 2009 | archive-date = 28 March 2020 | archive-url = https://web.archive.org/web/20200328181644/http://wcco.com/national/Rep.Patrick.Kennedy.2.267357.html }} "I simply do not remember getting out of bed, being pulled over by the police, or being cited for three driving infractions," Kennedy said. {{As of|2009}}, nonmedical use of zolpidem is common for some adolescents. Some users have reported decreased anxiety, mild [euphoria](/source/Euphoria_(emotion)), perceptual changes, visual distortions, and hallucinations.{{cite news |url=https://www.ksl.com/article/588181 |title=Ambien Abuse on Rise Among Teens |work=KSL |access-date=22 June 2009 |vauthors=Mulvihill K |archive-url=https://web.archive.org/web/20090220085827/http://www.ksl.com/index.php?nid=248&sid=588181 |archive-date=20 February 2009 | url-status=live }}{{cite journal | vauthors = Ford JA, McCutcheon J | title = The misuse of Ambien among adolescents: prevalence and correlates in a national sample | journal = Addictive Behaviors | volume = 37 | issue = 12 | pages = 1389–94 | date = December 2012 | pmid = 22795592 | doi = 10.1016/j.addbeh.2012.06.015 }} Zolpidem was used by Australian Olympic swimmers at the London Olympics in 2012, leading to controversy.{{cite news | url = http://www.abc.net.au/news/2013-08-23/australian-olympic-committee-will-not-punish-swimmers-further/4908278 | title = Swimming Australia's 'Stilnox six' given final warning as AOC decides not to issue any further sanctions | newspaper = ABC News | date = 23 August 2013 | publisher = www.abc.net.au | access-date = 3 August 2016 | archive-date = 7 August 2018 | archive-url = https://web.archive.org/web/20180807072707/http://www.abc.net.au/news/2013-08-23/australian-olympic-committee-will-not-punish-swimmers-further/4908278 | url-status = live }} === International travel === Zolpidem is among the agents used in the short-term management of insomnia associated with [jet lag](/source/jet_lag), typically at doses of 5–10 mg. Its clinical use, similar to that of other hypnotics, is constrained by the potential for adverse effects and dependence, and guidelines generally recommend limiting treatment duration to short periods, usually under one week.{{cite journal | vauthors = Beros A, Farquhar C, Nagels HE, Showell MG, Fernando A, Jordan V | title = Pharmacological interventions for jet lag. | journal = The Cochrane Database of Systematic Reviews | date = October 2021 | volume = 10 | article-number = CD014611 | pmc = 8527561 | doi = 10.1002/14651858.CD014611 }} ===Regulation=== For the stated reason of its potential for recreational use and dependence, zolpidem (along with the other benzodiazepine-like [Z-drug](/source/Z-drug)s) is a schedule IV substance under the [Controlled Substances Act](/source/Controlled_Substances_Act) in the US. The United States patent for zolpidem was held by the French pharmaceutical corporation [Sanofi-Aventis](/source/Sanofi-Aventis).{{Ref patent | country = US | number = 4382938 | title = Imidazo[1,2-a] pyridine derivatives and their application as pharmaceuticals | pubdate = 10 May 1983 | gdate = 17 July 1984 | inventor = Kaplan J-P, George P | assign1 = Synthelabo }} ===Use in crime=== The [Z-drugs](/source/Z-drugs), including zolpidem, have been used as [date rape drug](/source/date_rape_drug)s.{{cite news |title=Zolpidem most frequently used date rape drug in Korea |url=http://www.koreaherald.com/view.php?ud=20160229001119 |work=The Korea Herald |date=29 February 2016 |access-date=19 August 2018 |archive-date=19 August 2018 |archive-url=https://web.archive.org/web/20180819214258/http://www.koreaherald.com/view.php?ud=20160229001119 |url-status=live }} Zolpidem is available by prescription, and broadly prescribed unlike other date rape drugs: [gamma-hydroxybutyrate](/source/gamma-hydroxybutyrate) (GHB), which is used to treat [narcolepsy](/source/narcolepsy), or [flunitrazepam](/source/flunitrazepam) (Rohypnol), which is only prescribed as a second-line choice for insomnia. Zolpidem can be detected in bodily fluids for 36 hours, though it may be possible to detect it by [hair testing](/source/hair_testing) much later, which is due to the short [elimination half-life](/source/elimination_half-life) of 2.5–3 hours. This use of the drug was highlighted during proceedings against [Darren Sharper](/source/Darren_Sharper), who was accused of using the tablets he was prescribed to facilitate a series of rapes.{{cite news |url=https://www.usatoday.com/story/sports/nfl/2014/03/26/darren-sharper-ambien-zolpidem-insomnia-date-rape-case/6930621/ |title=Darren Sharper case spotlights sleep drug's dark side |work=USA Today |date=26 March 2014 |vauthors=Schrotenboer B |access-date=2 December 2017 |archive-date=28 February 2019 |archive-url=https://web.archive.org/web/20190228150428/https://www.usatoday.com/story/sports/nfl/2014/03/26/darren-sharper-ambien-zolpidem-insomnia-date-rape-case/6930621/ |url-status=live }}{{cite web |url=http://www.nydailynews.com/sports/football/drug-sharper-common-rapists-article-1.1616611 |title=In the rape case against Darren Sharper, former LAPD detective says Ambien is used often and can be similar to GHB |work=[New York Daily News](/source/New_York_Daily_News) |date=17 February 2014 |vauthors=Red C |access-date=7 April 2015 |archive-date=18 August 2018 |archive-url=https://web.archive.org/web/20180818084014/http://www.nydailynews.com/sports/football/drug-sharper-common-rapists-article-1.1616611 |url-status=live }} ===Sleepwalking and complex sleep behaviors=== Zolpidem has drawn significant media attention due to reports of complex sleep behaviors (CSBs), including sleepwalking, sleep-driving, and other activities performed while not fully conscious. Notable incidents include media reports in the United States concerning events such as Congressman [Patrick Kennedy's](/source/Patrick_J._Kennedy) motor vehicle accident{{cite web | vauthors = Stout D, Holusha J |title=Patrick Kennedy admits addiction after car crash |website=The New York Times |date=5 May 2006 |url=https://www.nytimes.com/2006/05/05/world/americas/05iht-web.0505kennedy.html |access-date=26 December 2024}}{{cite web |title=Kennedy's Crash Highlights Dangers of Ambien |website=ABC News |date=5 May 2006 |url=https://abcnews.go.com/Health/story?id=1927026&page=1 |access-date=26 December 2024}} and in Australia following a fatal {{convert|20|m|ft}} fall from the [Sydney Harbour Bridge](/source/Sydney_Harbour_Bridge) involving an individual reportedly under the influence of zolpidem.{{cite web | vauthors = Welch D |title=Did a sleeping pill end her brilliant life? |website=The Sydney Morning Herald |date=19 February 2008 |url=https://www.smh.com.au/national/did-a-sleeping-pill-end-her-brilliant-life-20080219-gds1ni.html |access-date=26 December 2024}}{{cite news | author = | date = 23 February 2007 | title = Stilnox blamed for Harbour Bridge death | newspaper = nineMSN News | url = http://news.ninemsn.com.au/article.aspx?id=381502 | archive-url = https://web.archive.org/web/20070615200018/http://news.ninemsn.com.au/article.aspx?id=381502 | archive-date = 15 June 2007}} In May 2018, actress [Roseanne Barr](/source/Roseanne_Barr) attributed a controversial remark on [Twitter](/source/Twitter) to the effects of zolpidem. Barr's tweet compared [Valerie Jarrett](/source/Valerie_Jarrett), a Black woman and former advisor to Barack Obama, to an ape. The comparison sparked widespread condemnation and led to the cancellation of ''[Roseanne](/source/Roseanne)''.{{cite web |vauthors=Koblin J |title=After Racist Tweet, Roseanne Barr's Show Is Canceled by ABC |website=The New York Times |date=29 May 2018 |url=https://www.nytimes.com/2018/05/29/business/media/roseanne-barr-offensive-tweets.html |access-date=26 December 2024 |archive-date=29 May 2018 |archive-url=https://web.archive.org/web/20180529214821/https://www.nytimes.com/2018/05/29/business/media/roseanne-barr-offensive-tweets.html |url-status=live }}{{cite web | vauthors = Chappell B |title=Roseanne Barr Says Ambien Played Role In Racist Tweet That Spiked Her Show's Reboot |website=NPR |date=30 May 2018 |url=https://www.npr.org/sections/thetwo-way/2018/05/30/615421269/roseanne-barr-says-ambien-played-role-in-racist-tweet-that-spiked-her-shows-rebo |access-date=26 December 2024}} The incident prompted [Sanofi](/source/Sanofi), the manufacturer of Ambien, to issue a public statement clarifying that "racism is not a known side effect" of the medication.{{cite web |vauthors=Hauser C |title=Roseanne Barr's Ambien Defense Is Disputed: 'Racism Is Not a Known Side Effect' |website=The New York Times |date=30 May 2018 |url=https://www.nytimes.com/2018/05/30/business/ambien-roseanne.html |access-date=26 December 2024 |archive-date=31 May 2018 |archive-url=https://web.archive.org/web/20180531044634/https://www.nytimes.com/2018/05/30/business/ambien-roseanne.html |url-status=live }} ===Brand names=== As of September 2018, zolpidem is marketed under many brands, examples include: Ambien 5 mg & 10 mg (IR [oral](/source/oral_administration) tablets), Ambien CR 6.25 mg & 12.5 mg ([controlled release](/source/Modified-release_dosage) tablets), Edluar 5 mg & 10 mg ([sublingual](/source/sublingual) tablets), Intermezzo 1.75 mg & 3.5 mg ([sublingual](/source/sublingual) tablets), and ZolpiMist 5 mg (oral spray).{{cite web|title=International brands for zolpidem|url=https://www.drugs.com/international/zolpidem.html|website=Drugs.com|access-date=15 March 2018|archive-date=12 June 2018|archive-url=https://web.archive.org/web/20180612141025/https://www.drugs.com/international/zolpidem.html|url-status=live}}{{cite web | vauthors = Cunha JP |title=Zolpidem |url=https://www.rxlist.com/zolpidem/generic-drug.htm |website=Rxlist.com |publisher=RxList Inc. |access-date=24 September 2025}} ==Research== While cases of zolpidem improving [aphasia](/source/aphasia) in people with [stroke](/source/stroke) have been described, use for this purpose has unclear benefits.{{cite journal | vauthors = de Boissezon X, Peran P, de Boysson C, Démonet JF | title = Pharmacotherapy of aphasia: myth or reality? | journal = Brain and Language | volume = 102 | issue = 1 | pages = 114–25 | date = July 2007 | pmid = 16982084 | doi = 10.1016/j.bandl.2006.07.004 | s2cid = 38304960 }} Zolpidem has also been studied in [persistent vegetative state](/source/persistent_vegetative_state)s with unclear effect.{{cite journal | vauthors = Georgiopoulos M, Katsakiori P, Kefalopoulou Z, Ellul J, Chroni E, Constantoyannis C | title = Vegetative state and minimally conscious state: a review of the therapeutic interventions | journal = Stereotactic and Functional Neurosurgery | volume = 88 | issue = 4 | pages = 199–207 | date = 2010 | pmid = 20460949 | doi = 10.1159/000314354 | doi-access = free | title-link = doi }} A 2017 [systematic review](/source/systematic_review) concluded that while there is preliminary evidence of benefit for treating disorders of movement and consciousness other than insomnia (including [Parkinson's disease](/source/Parkinson's_disease)), more research is needed.{{cite journal | vauthors = Bomalaski MN, Claflin ES, Townsend W, Peterson MD | title = Zolpidem for the Treatment of Neurologic Disorders: A Systematic Review | journal = JAMA Neurology | volume = 74 | issue = 9 | pages = 1130–1139 | date = September 2017 | pmid = 28655027 | doi = 10.1001/jamaneurol.2017.1133 | s2cid = 10756280 }} Animal studies in FDA files for zolpidem showed a dose dependent increase in some types of tumors, although the studies were too small to reach statistical significance.{{cite journal | vauthors = Kripke DF | title = Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit | journal = F1000Research | volume = 5 | page = 918 | date = 2016 | pmid = 27303633 | pmc = 4890308 | doi = 10.12688/f1000research.8729.1 | doi-access = free | title-link = doi }} Some observational epidemiological studies have found a correlation between use of benzodiazepines and certain [hypnotic](/source/hypnotic)s including zolpidem and an increased risk of getting cancer, but others have found no correlation; a 2017 meta-analysis of such studies found a correlation, stating that use of hypnotics was associated with a 29% increased risk of cancer, and that "zolpidem use showed the strongest risk of cancer" with an estimated 34% increased risk, but noted that the results were tentative because some of the studies failed to control for [confounder](/source/confounder)s like cigarette smoking and alcohol use, and some of the studies analyzed were [case–controls](/source/Case%E2%80%93control_study), which are more prone to some forms of bias.{{cite journal | vauthors = Kim DH, Kim HB, Kim YH, Kim JY | title = Use of Hypnotics and Risk of Cancer: A Meta-Analysis of Observational Studies | journal = Korean Journal of Family Medicine | volume = 39 | issue = 4 | pages = 211–218 | date = July 2018 | pmid = 29973038 | pmc = 6056405 | doi = 10.4082/kjfm.17.0025 }} Similarly, a meta-analysis of benzodiazepine drugs also shows their use is associated with increased risk of cancer.{{cite journal | vauthors = Kim HB, Myung SK, Park YC, Park B | title = Use of benzodiazepine and risk of cancer: A meta-analysis of observational studies | journal = International Journal of Cancer | volume = 140 | issue = 3 | pages = 513–525 | date = February 2017 | pmid = 27667780 | doi = 10.1002/ijc.30443 | doi-access = free | title-link = doi }} == References == {{Reflist}} == External links == {{Commons category|Zolpidem}} {{Hypnotics and sedatives}} {{Insomnia pharmacotherapies}} {{GABAAergics}} {{Portal bar|Medicine}} {{Authority control}} Category:Acetamides Category:Dimethylamino compounds Category:Drugs developed by Pfizer Category:GABAergic hallucinogens Category:GABAA receptor positive allosteric modulators Category:Hypnotics Category:Imidazopyridines Category:Medical controversies Category:Nonbenzodiazepines Category:Sanofi Category:Wikipedia medicine articles ready to translate --- Adapted from the Wikipedia article [Zolpidem](https://en.wikipedia.org/wiki/Zolpidem) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Zolpidem?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.