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Revision as of 20:59, 6 August 2011 view sourceBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit Latest revision as of 23:29, 8 December 2024 view source Oro Temp (talk | contribs)417 edits →Pharmacodynamics: Added that quetiapine is an antagonist to all of the serotonin receptors it has affinity for, except for at 5HT1A, where it acts as a partial agonist.Tag: Visual edit 
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{{Short description|Atypical antipsychotic medication}}
{{Drugbox| verifiedrevid = 420074643
{{Pp-semi-indef}}
|
{{Use dmy dates|date=January 2024}}
| IUPAC_name = 2-(2-(4-dibenzothiazepine- 11-yl- 1-piperazinyl)ethoxy)ethanol
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 443404910
| image = Quetiapine.svg | image = Quetiapine.svg
| width = 200px | width = 250
| alt =
| caption =
| image2 = Quetiapine-from-xtal-3D-balls.png | image2 = Quetiapine-from-xtal-3D-balls.png
| width2 = 150 | width2 = 225

| CASNo_Ref = {{cascite|correct|CAS}}
<!--Clinical data-->
| UNII_Ref = {{fdacite|correct|FDA}}
| pronounce = {{IPAc-en|k|w|ᵻ|ˈ|t|aɪ|.|ə|p|iː|n}} {{respell|kwi|TY|ə-peen}}
| UNII = BGL0JSY5SI
| tradename = Seroquel, Seroquel Xr, others
| InChI = 1/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2
| Drugs.com = {{drugs.com|monograph|quetiapine-fumarate}}
| InChIKey = URKOMYMAXPYINW-UHFFFAOYAD
| MedlinePlus = a698019
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| DailyMedID = Quetiapine
| ChEMBL = 716
| pregnancy_AU = B3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category =
| StdInChI = 1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2
| routes_of_administration = ]
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = URKOMYMAXPYINW-UHFFFAOYSA-N
| CAS_number = 111974-69-7
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4827
| ATC_prefix = N05 | ATC_prefix = N05
| ATC_suffix = AH04 | ATC_suffix = AH04
| class = ]
| ChEBI = 8707

| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_BR = C1
| legal_BR_comment = <ref>{{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=16 August 2023 |publisher=] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| legal_US_comment = <ref name="dailymed PI" /><ref>{{cite web | title=Seroquel Xr- quetiapine tablet, extended release | website=DailyMed | date=27 January 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=473a3ac4-67f4-4782-baa9-7f9bdd8761f4 | access-date=22 September 2024}}</ref>
| legal_status =

<!--Pharmacokinetic data-->
| bioavailability = 100%<ref name = Medscape />
| metabolism = ] via CYP3A4-catalysed sulfoxidation to its active metabolite norquetiapine (N-desalkylquetiapine)<ref name = GG>{{cite book| vauthors = Brunton L, Chabner B, Knollman B |title=Goodman and Gilman's The Pharmacological Basis of Therapeutics|edition=12th|publisher=McGraw Hill Professional|year=2010|isbn=978-0071624428|url=https://books.google.com/books?id=bVUfAQAAQBAJ}}</ref>
| protein_bound = 83%<ref name=EMC>{{cite web|title=Quetiapine 25 mg film-coated tablets - Summary of Product Characteristics|date=January 2013|access-date=20 October 2013|website=electronic Medicines Compendium|publisher=Sandoz|url=http://www.medicines.org.uk/emc/medicine/26575/SPC/Quetiapine+25+mg+film-coated+tablets/|url-status = dead|archive-url=https://web.archive.org/web/20131020062812/http://www.medicines.org.uk/emc/medicine/26575/SPC/Quetiapine+25+mg+film-coated+tablets/|archive-date=20 October 2013}}</ref>
| elimination_half-life = 7 hours (parent compound); 9–12 hours (active metabolite, norquetiapine)<ref name = EMC/><ref name = DD>Truven Health Analytics, Inc. DrugPoint System (Internet) . Greenwood Village, CO: Thomsen Healthcare; 2013.</ref>
| excretion = ] (73%), feces (20%)<ref name=Medscape>{{cite web|title=quetiapine (Rx) - Seroquel, Seroquel XR|url=http://reference.medscape.com/drug/seroquel-xr-quetiapine-342984#10|website=Medscape Reference|publisher=WebMD|access-date=11 October 2013|url-status = live|archive-url=https://web.archive.org/web/20131020163700/http://reference.medscape.com/drug/seroquel-xr-quetiapine-342984#10|archive-date=20 October 2013}}</ref><ref name = EMC/><ref name = DD /><ref name=DM>{{cite web|title=Quetiapine fumarate tablet |website=DailyMed|publisher=Ascend Laboratories, LLC|date=October 2013|access-date=26 November 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3112a006-1c61-47f2-84f5-9a7670d09c9b|url-status = live|archive-url=https://web.archive.org/web/20131202224630/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3112a006-1c61-47f2-84f5-9a7670d09c9b|archive-date=2 December 2013}}</ref>

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 111974-69-7
| PubChem = 5002 | PubChem = 5002
| IUPHAR_ligand = 50 | IUPHAR_ligand = 50
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01224 | DrugBank = DB01224
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4827
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BGL0JSY5SI
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08456 | KEGG = D08456
| ChEBI_Ref = {{ebicite|correct|EBI}}
| C=21|H=25|N=3|O=2|S=1
| ChEBI = 8707
| molecular_weight = 383.5099 g/mol
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| smiles = N\1=C(\c3c(Sc2c/1cccc2)cccc3)N4CCN(CCOCCO)CC4
| bioavailability = 9% | ChEMBL = 716

| metabolism = ]
<!--Chemical data-->
| elimination_half-life = 6 hours
| IUPAC_name = 2-(2-(4-Dibenzothiazepine-11-yl-1-piperazinyl)ethoxy)ethanol
| excretion = ]
| C = 21| H = 25| N = 3| O = 2| S = 1
| pregnancy_US = C
| SMILES = N\1=C(\c3c(Sc2c/1cccc2)cccc3)N4CCN(CCOCCO)CC4
| legal_US = Rx-only
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration = Oral
| StdInChI = 1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = URKOMYMAXPYINW-UHFFFAOYSA-N
| solubility = 3.29
}} }}


<!-- Definition and medical uses -->
'''Quetiapine''' ({{IPAc-en|icon|k|w|ɨ|ˈ|t|aɪ|.|ə|p|iː|n}} {{respell|kwi|TY|ə-peen}}) (branded as '''Seroquel''', '''Ketipinor'''), is an ] approved for the treatment of ], and ].
'''Quetiapine''', sold under the brand name '''Seroquel''' among others, is an ] medication used for the treatment of ], ], and ].<ref name=AHFS2017>{{cite web|title=Quetiapine Fumarate|url=https://www.drugs.com/monograph/quetiapine-fumarate.html|publisher=The American Society of Health-System Pharmacists|access-date=26 March 2017|url-status = live|archive-url=https://web.archive.org/web/20170829153057/https://www.drugs.com/monograph/quetiapine-fumarate.html|archive-date=29 August 2017}}</ref><ref name=Cochrane2010>{{cite journal | vauthors = Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S | title = Second-generation antipsychotics for major depressive disorder and dysthymia | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD008121 | date = December 2010 | pmid = 21154393 | doi = 10.1002/14651858.CD008121.pub2 }}</ref> Despite being widely used as a ] due to its ] effects, the benefits of such use may not outweigh the risk of undesirable side effects.<ref>{{cite journal | vauthors = Anderson SL, Vande Griend JP | title = Quetiapine for insomnia: A review of the literature | journal = American Journal of Health-System Pharmacy | volume = 71 | issue = 5 | pages = 394–402 | date = March 2014 | pmid = 24534594 | doi = 10.2146/ajhp130221 | url = https://pdfs.semanticscholar.org/8812/afd4bc713c03435b68f2bb6ea456c611b0b2.pdf | url-status = dead | s2cid = 207292819 | archive-url = https://web.archive.org/web/20200219013637/https://pdfs.semanticscholar.org/8812/afd4bc713c03435b68f2bb6ea456c611b0b2.pdf | archive-date = 19 February 2020 }}</ref> It is taken orally.<ref name=AHFS2017/>


<!-- Side effects and mechanism -->
Annual sales are approximately $5.7 billion worldwide, and $2.9 billion in the United States.<ref></ref> The U.S. patent<ref></ref>, which was set to expire in 2011, received a pediatric exclusivity extension which pushed its expiration to March 26, 2012.<ref></ref> The patent has already expired in Canada. There are now several ] versions of quetiapine, such as '''Quepin''' made by Specifar ABEE, Athens, Greece.<ref>{{cite web |url=http://www.theodora.com/drugs/quepin_tablets_specifar.html |title=Quepin Full Prescribing Information in Drug Reference Encyclopedia |work= |accessdate=2010-04-03}}</ref>
Common side effects include ], ], weight gain, ], and ].<ref name=AHFS2017/> Other side effects include ], ], a ], ], ], and ].<ref name=AHFS2017/> In older people with ], its use increases the risk of death.<ref name=AHFS2017/> Use in the ] of ] may result in a ] in the baby for some time after birth.<ref name=AHFS2017/> Quetiapine is believed to work by blocking a number of receptors, including those for ] and ].<ref name=AHFS2017/>


<!-- History and culture -->
== Medical uses ==
Quetiapine was developed in 1985 and was approved for medical use in the United States in 1997.<ref name="dailymed PI" /><ref name=AHFS2017/><ref>{{cite journal | vauthors = Riedel M, Müller N, Strassnig M, Spellmann I, Severus E, Möller HJ | title = Quetiapine in the treatment of schizophrenia and related disorders | journal = Neuropsychiatric Disease and Treatment | volume = 3 | issue = 2 | pages = 219–235 | date = April 2007 | pmid = 19300555 | pmc = 2654633 | doi = 10.2147/nedt.2007.3.2.219 | doi-access = free }}</ref> It is available as a ].<ref name=BNF74>{{cite book|title=British national formulary: BNF 74|date=2017|publisher=British Medical Association|isbn=978-0857112989|page=383|edition=74}}</ref> In 2022, it was the 82nd most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Quetiapine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Quetiapine | access-date = 30 August 2024 }}</ref> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>
] coin for comparison.]]


==Medical uses==
Quetiapine is used to treat either ] or ].<ref name=AHFS>{{cite web|title=quetiapine-fumarate|url=http://www.drugs.com/monograph/quetiapine-fumarate.html|work=The American Society of Health-System Pharmacists|accessdate=3 April 2011}}</ref>
] coin for comparison]]
]


Quetiapine is primarily used to treat schizophrenia or bipolar disorder.<ref name=AHFS>{{cite web|title=quetiapine-fumarate|url=https://www.drugs.com/monograph/quetiapine-fumarate.html|website=The American Society of Health-System Pharmacists|access-date=3 April 2011|url-status = live|archive-url=https://web.archive.org/web/20110210181855/http://www.drugs.com/monograph/quetiapine-fumarate.html|archive-date=10 February 2011}}</ref> Quetiapine targets both positive and negative symptoms of schizophrenia.<ref name="Quetiapine">{{cite journal | vauthors = Dev V, Raniwalla J | title = Quetiapine: a review of its safety in the management of schizophrenia | journal = Drug Safety | volume = 23 | issue = 4 | pages = 295–307 | date = October 2000 | pmid = 11051217 | doi = 10.2165/00002018-200023040-00003 }}</ref>
In those with bipolar it is used for depressive episodes, acute manic episodes associated with ] (as either monotherapy or adjunct therapy to ] or ]), and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).<ref name="Thase MacFadden Weisler Chang et al : Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression">{{cite doi|10.1097/01.jcp.0000248603.76231.b7}}</ref>


===Schizophrenia===
It is sometimes used ], often as an augmentation agent, to treat conditions such as ], ], ], ], ], ],<ref name="Croissant Klein Gehrlein Kniest et al : Quetiapine in relapse prevention in alcoholics suffering from craving and affective symptoms: a case series">{{cite doi|10.1016/j.eurpsy.2006.04.007
A 2013 Cochrane ] compared quetiapine to typical antipsychotics:
}}</ref> ],<ref name="Mukaddes Abali : Quetiapine Treatment of Children and Adolescents with Tourette's Disorder">{{cite doi|10.1089/104454603322572624}}</ref> and has been used by physicians as a ] for those with ]s or ]s.<ref name="Becker : Treatment of sleep dysfunction and psychiatric disorders">{{cite doi|10.1007/s11940-006-0026-6}}</ref>
{| class="wikitable"
|+ Quetiapine compared to typical antipsychotics for schizophrenia<ref name=Sut2013>{{cite journal | vauthors = Suttajit S, Srisurapanont M, Xia J, Suttajit S, Maneeton B, Maneeton N | title = Quetiapine versus typical antipsychotic medications for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 5 | issue = 5 | pages = CD007815 | date = May 2013 | pmid = 23728667 | doi = 10.1002/14651858.CD007815.pub2 | url = http://www.cochrane.org/CD007815/SCHIZ_quetiapine-versus-typical-antipsychotic-drugs-for-schizophrenia | url-status = live | archive-url = https://web.archive.org/web/20160421052117/http://www.cochrane.org/CD007815/SCHIZ_quetiapine-versus-typical-antipsychotic-drugs-for-schizophrenia | archive-date = 21 April 2016 }}</ref>
|-
! Summary
|-
|Quetiapine may not differ from typical ]s in the treatment of ], general psychopathology, and ]. However, it causes fewer adverse effects in terms of abnormal ], ] effects, abnormal prolactin levels and weight gain.<ref name=Sut2013/>
|-
| style="padding:0;" |
{| class="wikitable collapsible collapsed" style="width:100%;"
|-
! scope="col" style="text-align: left;"| Outcome
! scope="col" style="text-align: left;"| Findings in words
! scope="col" style="text-align: left;"| Findings in numbers
! scope="col" style="text-align: left;"| Quality of evidence
|-
! colspan="4" style="text-align: left;"| Global state
|-
| No clinical significant response || There is no clear difference between people given quetiapine and those receiving typical antipsychotic drugs. These findings are based on data of moderate quality. || ] 0.96 (0.75 to 1.23) || ]
|-
! colspan="4" style="text-align: left;"|Mental state
|-
| Average ] score (])|| On average, people receiving quetiapine scored higher (worse) than people treated with typical antipsychotic drugs. There was, however, no clear difference between the groups. This finding is based on data of moderate quality. || ] 0.02 higher (0.39 lower to 0.43 higher)* || ]
|-
| Average ] score (])|| On average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. This finding is based on data of moderate quality. || ] 0.82 lower (1.59 to 0.04 lower)* || ]
|-
! colspan="4" style="text-align: left;"| ]
|-
| Average score|| On average, people receiving quetiapine scored higher (better) than people treated with typical antipsychotic drugs. There was no clear difference between the groups. This finding is based on data of very limited quality. || ] 1.55 higher (0.62 lower to 3.72 higher)* || ]
|-
! colspan="4" style="text-align: left;"| Leaving the study early
|-
| For any reason || Quetiapine is not clearly more acceptable than typical antipsychotic drugs. These findings are based on data of moderate quality. || ] 0.91 (0.81 to 1.01) || ]
|-
! colspan="4" style="text-align: left;"| Adverse effects
|-
| Extrapyramidal effects || Quetiapine may reduce the chance of experiencing these movement disorders. This finding is based on data of moderate quality. || ] 0.17 (0.09 to 0.32) || ]
|-
| Prolactin level<br />Average level (ng/mL) || On average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. There was a clear difference between the groups. This finding is based on data of moderate quality.|| ] 16.20 lower (23.34 to 9.07 lower)* || ]
|-
| || *The meaning of these findings for day-to-day care is not clear || ||
|}
|}


In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13–16% more effective than ], ], and ] and approximately as effective as ] and ].<ref name=Lancet/>
In 2005, the National Institute of Mental Health examined quetiapine and other antipsychotics to uncover the comparative efficacy of "second generation" anti-psychotics against older anti-psychotics (known as "first generation" or "typical anti-psychotics"). Such information could be important to the patients, as the newer drugs are far more expensive than their older counterparts. Published in the New England Journal of Medicine, the results of the CATIE ("clinical antipsychotic trials of interventional effectiveness") trial were somewhat mixed. 74% of trial participants (of the 1,493 people who were in different treatment groups) discontinued before the trial ended. The majority of the participants discontinued treatment due to intolerable side-effects or lack of efficacy. ] (Zyprexa) was considered the most effective in terms of the time it took patients to drop out of the study, although it was associated with greater weight gain and ] intolerability found in diabetes patients. The effects of all other treatments (such as Seroquel) were considered to be similar to the effects of the generic (and dramatically less expensive) drug, ].<ref name="Lieberman Stroup McEvoy Swartz et al : Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia">{{cite doi|10.1056/NEJMoa051688}}</ref>


There is tentative evidence of the benefit of quetiapine versus placebo in schizophrenia; however, definitive conclusions are not possible due to the high rate of attrition in trials (greater than 50%) and the lack of data on economic outcomes, social functioning, or quality of life.<ref name=Coch2004>{{cite journal | vauthors = Srisurapanont M, Maneeton B, Maneeton N | title = Quetiapine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD000967 | year = 2004 | volume = 2004 | pmid = 15106155 | pmc = 7032613 | doi = 10.1002/14651858.CD000967.pub2 | veditors = Srisurapanont M }}</ref>
Quetiapine is ineffective in reducing agitation among ] patients, whose usage of the drug constituted 29% of sales. In fact, quetiapine was found to worsen cognitive functioning in elderly patients with dementia.<ref name="Ballard Margallo-Lana Juszczak Douglas et al : Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial">{{cite doi|10.1136/bmj.38369.459988.8F}}</ref>


It is debatable whether, as a class, ] or ]s are more effective.<ref>{{cite journal | vauthors = Kane JM, Correll CU | title = Pharmacologic treatment of schizophrenia | journal = Dialogues in Clinical Neuroscience | volume = 12 | issue = 3 | pages = 345–357 | year = 2010 | pmid = 20954430 | pmc = 3085113 | doi = 10.31887/DCNS.2010.12.3/jkane }}</ref> Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages.<ref name=AFP07>{{cite journal | vauthors = Schultz SH, North SW, Shields CG | title = Schizophrenia: a review | journal = American Family Physician | volume = 75 | issue = 12 | pages = 1821–1829 | date = June 2007 | pmid = 17619525 }}</ref> While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.<ref name=Coch2004/>
==Adverse effects==
The most common ] of quetiapine is ]. Other common side-effects include: sluggishness, fatigue, dry mouth, sore throat, dizziness, abdominal pain, constipation, upset stomach, ], inflammation or swelling of the sinuses or pharynx, increased appetite, and weight gain.<ref>http://www1.astrazeneca-us.com/pi/Seroquel.pdf</ref>


A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than ] and ]; produce fewer movement related side effects than ], ], ], risperidone and olanzapine; and produce weight gain similar to risperidone, ] and aripiprazole. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, ]; ]; sedation; ]; ], ] and ] at a rate similar to first generation antipsychotics.<ref name="Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S 2013 CD006625">{{cite journal | vauthors = Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S | title = Quetiapine versus other atypical antipsychotics for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD006625 | date = November 2013 | pmid = 24249315 | pmc = 4167871 | doi = 10.1002/14651858.CD006625.pub3 }}</ref>
It is marketed as one of the most sedating of all anti-psychotics, although those claims are contested.<ref name="WSP">{{cite news|title=A Silenced Drug Study Creates An Uproar|work=]|date=2009-03-18|author=Shankar Vedantam|url=http://www.washingtonpost.com/wp-dyn/content/article/2009/03/17/AR2009031703786.html}}</ref> Beginning users may feel extremely tired and 'out of it' for the first few days, and sometimes longer. Quetiapine's newest indication, for ] depression, usually specifically calls for the entire dose to be taken before bedtime due to its sedative effects. The sedative effects may disappear after some time on the drug, or with a change of dosage, and with possibly different, non-sedative side-effects emerging.


===Bipolar disorder===
As with most neuroleptic antipsychotics, the prolonged use of high doses (over 200&nbsp;mg) of quetiapine increases the risk of the patient developing ], an incurable ].<ref>{{cite journal|author=S. Nassir Ghaemi and James Y. Ko|month=October|year=2001|journal= Am J Psychiatry|volume=158|issue=10|pages=1737|title=quetiapine-related tardive dyskinesia|pmid=11579018|doi=10.1176/appi.ajp.158.10.1737}}</ref><ref>{{cite journal|title=Tardive dyskinesia with quetiapine|journal=Am J Psychiatry|date=May 1999|volume=156|issue=5|pages=796&ndash;797|author=D. Ghelber and R.H. Belmaker|pmid=10327920}}</ref> The risk of suffering tardive dyskinesia becomes greater the longer Seroquel treatment continues, so patients may want to consider alternate options before using Seroquel, especially if in a high-risk category.<ref>http://www.tardive-dyskinesia.com/seroquel/</ref>
In those with ], quetiapine is used to treat depressive episodes; acute manic episodes associated with ] (as either monotherapy or adjunct therapy to ]; ] or ]); acute mixed episodes; and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).


===Major depressive disorder===
The rare, but life-threatening, ] may also result from quetiapine use.
Quetiapine is effective when used by itself<ref name =Cochrane2010/> and when used along with other medications in ] (MDD).<ref name =Cochrane2010/><ref>{{cite journal | vauthors = Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC | title = Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes | journal = PLOS Medicine | volume = 10 | issue = 3 | pages = e1001403 | year = 2013 | pmid = 23554581 | pmc = 3595214 | doi = 10.1371/journal.pmed.1001403 | doi-access = free }}</ref> However, sedation is often an undesirable side effect.<ref name =Cochrane2010/>


In the United States,<ref name = "DD" /> the United Kingdom<ref name = "BNF 65" /> and Australia (while not subsidised by the Australian ] for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD.<ref name = "AMH">{{cite book | title = Australian Medicines Handbook | year = 2013 | publisher = The Australian Medicines Handbook Unit Trust | isbn = 978-0-9805790-9-3 | edition = 2013 | place = Adelaide | veditors = Rossi S | url = https://books.google.com/books?id=tn3-swEACAAJ }}</ref>
Weight gain can be a problem for some patients, as quetiapine causes the patient's appetite to persist even after meals. However, this effect may occur to a lesser degree compared to some other atypical anti-psychotics such as ] or ]. {{Citation needed|date=June 2010}}


===Alzheimer's disease===
Studies conducted on ]s have resulted in the formation of ]s. While there are reports of cataracts occurring in humans, controlled studies including thousands of patients have not demonstrated a clear causal association between quetiapine therapy and this side-effect. (Reference needed to April 2006 results of CATIE study.) However, the Seroquel website<ref></ref> still recommends users have eye examinations every six months.
Quetiapine does not decrease agitation among people with ]. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.<ref name="Ballard Margallo-Lana Juszczak Douglas et al : Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial">{{cite journal | vauthors = Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, O'Brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish R, Jacoby R | title = Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial | journal = BMJ | volume = 330 | issue = 7496 | pages = 874 | date = April 2005 | pmid = 15722369 | pmc = 556156 | doi = 10.1136/bmj.38369.459988.8F }}</ref>


===Insomnia===
As with some other anti-psychotics, quetiapine may lower the seizure threshold, and should be taken with caution in combination with drugs such as ].
The use of low doses of quetiapine for ], while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.<ref name="pmid22510671">{{cite journal | vauthors = Coe HV, Hong IS | title = Safety of low doses of quetiapine when used for insomnia | journal = The Annals of Pharmacotherapy | volume = 46 | issue = 5 | pages = 718–722 | date = May 2012 | pmid = 22510671 | doi = 10.1345/aph.1Q697 | s2cid = 9888209 }}</ref><ref name="pmid24534594">{{cite journal | vauthors = Anderson SL, Vande Griend JP | title = Quetiapine for insomnia: A review of the literature | journal = American Journal of Health-System Pharmacy | volume = 71 | issue = 5 | pages = 394–402 | date = March 2014 | pmid = 24534594 | doi = 10.2146/ajhp130221 }}</ref><ref name="pmid33941603">{{cite journal | vauthors = Modesto-Lowe V, Harabasz AK, Walker SA | title = Quetiapine for primary insomnia: Consider the risks | journal = Cleveland Clinic Journal of Medicine | volume = 88 | issue = 5 | pages = 286–294 | date = May 2021 | pmid = 33941603 | doi = 10.3949/ccjm.88a.20031 | doi-access = free }}</ref><ref name="pmid22132426">{{cite report | vauthors = Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ, Ewing BA, Motala A, Perry T | title = Off-Label Use of Atypical Antipsychotics: An Update | date = September 2011 | pmid = 22132426 }}</ref><ref name="Off-Label Use">{{cite book |title=Off-Label Use of Atypical Antipsychotics: An Update |vauthors=Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ |publisher=Agency for Healthcare Research and Quality |year=2011 |series=Comparative Effectiveness Reviews, No. 43 |location=Rockville |pmid=22973576}}</ref><ref>{{cite journal | vauthors = Coe HV, Hong IS | title = Safety of low doses of quetiapine when used for insomnia | journal = The Annals of Pharmacotherapy | volume = 46 | issue = 5 | pages = 718–722 | date = May 2012 | pmid = 22510671 | doi = 10.1345/aph.1Q697 | s2cid = 9888209 }}</ref> A 2022 network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine did not demonstrate any short-term benefits in sleep quality. Quetiapine, specifically, had an ] (]) against ] for treatment of insomnia of 0.05 (95% {{Abbrlink|CI|confidence interval}} –1.21 to 1.11) at 4{{nbsp}}weeks of treatment, with the ] rated as very low.<ref>{{cite journal | vauthors = De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A | title = Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis | language = English | journal = Lancet | volume = 400 | issue = 10347 | pages = 170–184 | date = July 2022 | pmid = 35843245 | doi = 10.1016/S0140-6736(22)00878-9 | s2cid = 250536370 | doi-access = free | hdl = 11380/1288245 | hdl-access = free }}</ref> Doses of quetiapine used for insomnia have ranged from 12.5 to 800{{nbsp}}mg, with low doses of 25 to 200{{nbsp}}mg being the most typical.<ref name="pmid19299326">{{cite journal | vauthors = Wine JN, Sanda C, Caballero J | title = Effects of quetiapine on sleep in nonpsychiatric and psychiatric conditions | journal = The Annals of Pharmacotherapy | volume = 43 | issue = 4 | pages = 707–713 | date = April 2009 | pmid = 19299326 | doi = 10.1345/aph.1L320 | s2cid = 207263320 }}</ref><ref name="pmid22510671" /><ref name="pmid24534594" /> Regardless of the dose used, some of the more serious adverse effects may still possibly occur at the lower dosing ranges, such as ] and ].<ref>{{cite journal | vauthors = Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, Beck K, Natesan S, Efthimiou O, Cipriani A, Howes OD | title = Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis | journal = The Lancet. Psychiatry | volume = 7 | issue = 1 | pages = 64–77 | date = January 2020 | pmid = 31860457 | pmc = 7029416 | doi = 10.1016/s2215-0366(19)30416-x }}</ref><ref>{{cite journal | vauthors = Yoshida K, Takeuchi H | title = Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia | journal = Behavioural Brain Research | volume = 402 | pages = 113098 | date = March 2021 | pmid = 33417992 | doi = 10.1016/j.bbr.2020.113098 | s2cid = 230507941 | doi-access = free }}</ref> These safety concerns at low doses are corroborated by Danish observational studies that showed use of specifically low-dose quetiapine (prescriptions filled for tablet strengths >50 mg were excluded) was associated with an increased risk of major cardiovascular events as compared to use of ], with most of the risk being driven by cardiovascular death.<ref>{{cite journal | vauthors = Højlund M, Andersen K, Ernst MT, Correll CU, Hallas J | title = Use of low-dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator-controlled cohort study | journal = World Psychiatry | volume = 21 | issue = 3 | pages = 444–451 | date = October 2022 | pmid = 36073694 | pmc = 9453914 | doi = 10.1002/wps.21010 }}</ref> Laboratory data from an unpublished analysis of the same cohort also support the lack of dose-dependency of metabolic side effects, as new use of low-dose quetiapine was associated with a risk of increased fasting triglycerides at 1-year follow-up.<ref>{{cite thesis | vauthors = Højlund M | degree = Ph.D. | publisher = University of Southern Denmark |date=12 September 2022 |title=Low-dose Quetiapine: Utilization and Cardiometabolic Risk |url= https://portal.findresearcher.sdu.dk/en/publications/low-dose-quetiapine-utilization-and-cardiometabolic-risk |language=English |doi=10.21996/mr3m-1783}}</ref>


===Others===
A recent comparative study of anti-psychotics drugs has found that quetiapine mono treatment was associated with increased risk of death relative to the other analyzed treatments.<ref name="Tiihonen Lönnqvist Wahlbeck Klaukka et al : 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study)">{{cite doi|10.1016/S0140-6736(09)60742-X}}</ref>


It is sometimes used ], often as an augmentation agent, to treat conditions such as ],<ref name="Mukaddes_2013">{{cite journal | vauthors = Mukaddes NM, Abali O | title = Quetiapine treatment of children and adolescents with Tourette's disorder | journal = Journal of Child and Adolescent Psychopharmacology | volume = 13 | issue = 3 | pages = 295–299 | year = 2003 | pmid = 14642017 | doi = 10.1089/104454603322572624 }}</ref> ]<ref>Oliver Sacks "Musicophilia" Knopf NY 2007 P.67</ref> and ]s.<ref name="Becker : Treatment of sleep dysfunction and psychiatric disorders">{{cite journal | vauthors = Becker PM | title = Treatment of sleep dysfunction and psychiatric disorders | journal = Current Treatment Options in Neurology | volume = 8 | issue = 5 | pages = 367–375 | date = September 2006 | pmid = 16901376 | doi = 10.1007/s11940-006-0026-6 | s2cid = 34246401 }}</ref>
Quetiapine strongly affects the adrenergic system (]) and can therefore cause problems with ]<ref>{{cite journal|author=Shibata M, Einhaus S, Schweitzer JB, Zuckerman S, Leffler CW|month=November|year=1993|journal= Journal of Neurosurgery|volume=79|issue=5|pages=696–704|title=Cerebral blood flow decreased by adrenergic stimulation of cerebral vessels in anesthetized newborn pigs with traumatic brain injury|pmid=8105043|doi=}}</ref> and ] in general.


Quetiapine and ] are the most widely used medications for the treatment of ] psychosis due to their relatively low extrapyramidal side-effect liability.<ref>{{cite journal | vauthors = Kyle K, Bronstein JM | title = Treatment of psychosis in Parkinson's disease and dementia with Lewy Bodies: A review | journal = Parkinsonism & Related Disorders | volume = 75 | pages = 55–62 | date = June 2020 | pmid = 32480308 | doi = 10.1016/j.parkreldis.2020.05.026 | quote = In clinical practice, quetiapine is more readily used than clozapine, given its improved side effect profile compared to clozapine. Despite frequent use in clinical practice, its efficacy in PDP is less clear.&nbsp;... The quetiapine evidence base is thus ambiguous, lacking consistent support from RCTs in PDP. In DLB there is reliance upon retrospective studies, with the inherent limitations therein. As with clozapine, sedation and orthostasis can be limiting factors. In clinical practice, despite the paucity of consistent evidence, quetiapine has been the first line antipsychotic therapy due to its side effect profile and lower neuroleptic sensitivity risk. | s2cid = 219168745 }}</ref> Owing to the risks associated with clozapine (e.g. agranulocytosis, diabetes mellitus, etc.), clinicians often attempt treatment with quetiapine first, although the evidence to support quetiapine's use for this indication is significantly weaker than that of clozapine.<ref>{{cite journal | vauthors = Shotbolt P, Samuel M, David A | title = Quetiapine in the treatment of psychosis in Parkinson's disease | journal = Therapeutic Advances in Neurological Disorders | volume = 3 | issue = 6 | pages = 339–350 | date = November 2010 | pmid = 21179595 | pmc = 3002640 | doi = 10.1177/1756285610389656 }}</ref><ref name = Maudsley/>
An occasionally reported side-effect of quetiapine is ] possibly accompanied by ]. The likelihood of this occurrence increases when combined with the intake of alcohol or when the user tries to fight off the sedation caused by larger doses of quetiapine.


==Adverse effects==
Long-term use may cause brain damage or reduce life expectancy - see ] for details.
Sources for incidence lists:<ref name = Medscape /><ref name = "DD"/><ref name = "BNF 65">{{cite book|title=British National Formulary (BNF) 65|year=2013|publisher=Pharmaceutical Press|location=London, UK|isbn=9780857110848|page=235|url=https://books.google.com/books?id=fZLvtHELVdMC}}</ref><ref name = AMH /><ref name = Maudsley>{{cite book| vauthors = Taylor D, Carol P, Shitij K |title=The Maudsley prescribing guidelines in psychiatry|year=2012|publisher=Wiley-Blackwell|location=West Sussex|isbn=9780470979693|url=https://books.google.com/books?id=KY_2Qk4LqVYC}}</ref><ref name=TGA>{{cite web |title= PRODUCT INFORMATION STADA(TM) Quetiapine (quetiapine fumarate Tablets 25 mg, 100 mg, 200 mg, 300 mg)|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-03014-1|date=30 November 2012|access-date=19 September 2013|website=TGA eBusiness Services|publisher=STADA Pharmaceuticals Australia Pty Limited|url-status = live|archive-url=https://web.archive.org/web/20170327075724/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2012-PI-03014-1|archive-date=27 March 2017}}</ref>


;Very common (>10% incidence) adverse effects
===Discontinuation ===
* Dry mouth
Quetiapine should be discontinued gradually, with careful consideration from the prescribing doctor, to avoid withdrawal symptoms or relapse.
* Dizziness
* Headache
* ] (drowsiness; of 15 antipsychotics quetiapine causes the 5th most sedation. Extended release (XR) formulations tend to produce less sedation, dose-by-dose, than the immediate release formulations.)<ref name=Lancet>{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref>


;Common (1–10% incidence) adverse effects
The ] recommends a gradual withdrawal when discontinuing anti-psychotic treatment to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192"/> Due to compensatory changes at dopamine, serotonin, adrenergic and histamine receptor sites in the central nervous system, withdrawal symptoms can occur during abrupt or over-rapid reduction in dosage. Withdrawal symptoms reported to occur after discontinuation of quetiapine include nausea, ], lightheadedness, ], ], ], ], nervousness, dizziness, headache, excessive non-stop crying, and ]. The present evidence suggests that these symptoms affect a small number of susceptible individuals treated with Quetiapine.<ref name="Kim-2005"/><ref name="Michaelides-2005">{{Cite journal | last1 = Michaelides | first1 = C. | last2 = Thakore-James | first2 = M. | last3 = Durso | first3 = R. | title = Reversible withdrawal dyskinesia associated with quetiapine. | journal = Mov Disord | volume = 20 | issue = 6 | pages = 769–70 | month = Jun | year = 2005 | doi = 10.1002/mds.20427 | pmid = 15747370 }}</ref> Complicated and long-lasting ] symptoms can also occur after withdrawing from quetiapine.{{Citation needed|date=June 2010}}
{{colbegin|colwidth=15em}}
* ]
* ]
* ]
* ]
* Elevated serum triglycerides
* Abdominal pain
* Constipation
* Increased appetite
* Vomiting
* Increased liver enzymes
* Backache
* ]
* Insomnia
* Lethargy
* Tremor
* Agitation
* Nasal congestion
* ]
* Fatigue
* Pain
* ] (Indigestion)
* Peripheral ]
* ]
{{colend}}
* ]: Quetiapine and clozapine are noted for their relative ''lack'' of extrapyramidal side effects.<ref name = Lancet /><ref name = "BNF 65" /><ref name = Maudsley />
* Weight gain: ] 0.43&nbsp;kg when compared to placebo. Produces roughly as much weight gain as ], less weight gain than ], ] and ] and more weight gain than ], ], ] and ].<ref name = Lancet /> As with many other atypical antipsychotics, this action is likely due to its actions at the ] and ].<ref name = GG />


;Rare (<1% incidence) adverse effects
===Overdosage===
{{Div col|colwidth=30em}}
Most instances of acute overdosage result only in sedation, hypotension and tachycardia, but cardiac arrythmia, coma and death have occurred in adults. Serum or plasma quetiapine concentrations are usually in the 1–10&nbsp;mg/L range in overdose survivors, while postmortem blood levels of 10–25&nbsp;mg/L are generally observed in fatal cases.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1355–1357.</ref>
* Prolonged ] (had an odds ratio for prolonging the QT interval over placebo of 0.17)<ref name = "Lancet" />
* ]
* ]
* ]
* ]
* ], low blood sodium.
* ], yellowing of the eyes, skin and mucous membranes due to an impaired ability of the body to clear bilirubin, a by product of haem breakdown.
* ], pancreas swelling.
* ], a potentially fatal drop in white blood cell count.
* ], a drop in white blood cell count, not as severe as agranulocytosis.
* ], a drop in neutrophils, the cell of the immune cells that defends the body against bacterial infections.
* ]
* ], a potentially fatal allergic reaction.
* ]
* ], underactive thyroid gland.
* ], swelling of the myocardium.
* ]
* ], swelling of the liver.
* ]
* ]. A prolonged and painful erection.
* ]. A potentially fatal skin reaction.
{{colend}}
* ] a rare and potentially fatal complication of antipsychotic drug treatment. It is characterised by the following symptoms: tremor, rigidity, hyperthermia, tachycardia, mental status changes (e.g. confusion), etc.
* ]. A rare and often irreversible neurological condition characterised by involuntary movements of the face, tongue, lips and rest of the body. Most commonly occurs after prolonged treatment with antipsychotics. It is believed to be particularly uncommon with atypical antipsychotics, especially quetiapine and clozapine<ref name="AMH"/>


Both typical and atypical antipsychotics can cause ].<ref name=TD08>{{cite journal | vauthors = Correll CU, Schenk EM | title = Tardive dyskinesia and new antipsychotics | journal = Current Opinion in Psychiatry | volume = 21 | issue = 2 | pages = 151–156 | date = March 2008 | pmid = 18332662 | doi = 10.1097/YCO.0b013e3282f53132 | s2cid = 37288246 }}</ref> According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%.<ref name=TD08/> Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.<ref>{{cite journal | vauthors = Aia PG, Revuelta GJ, Cloud LJ, Factor SA | title = Tardive dyskinesia | journal = Current Treatment Options in Neurology | volume = 13 | issue = 3 | pages = 231–241 | date = June 2011 | pmid = 21365202 | doi = 10.1007/s11940-011-0117-x | s2cid = 24308129 }}</ref>
==Pharmacology==
Quetiapine has the following pharmacological actions:<ref name = Seroquel>{{Cite journal|author=]|id=276521 |title=Seroquel (quietapine fumarate) tablets |url=http://www1.astrazeneca-us.com/pi/Seroquel.pdf |format=]}}</ref><ref name="pmid11132243">{{cite journal | author = Richelson E, Souder T | title = Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds | journal = Life Sciences | volume = 68 | issue = 1 | pages = 29–39 | year = 2000 | month = November | pmid = 11132243 | doi = 10.1016/S0024-3205(00)00911-5| url = http://linkinghub.elsevier.com/retrieve/pii/S0024320500009115}}</ref><ref name="urlNeuropsychopharmacology: the fifth ... - Google Books">{{cite book | url = http://books.google.com/?id=BKwkonZwZD0C&pg=PA778#v=onepage&q= | title = Neuropsychopharmacology: the fifth ... - Google Books | format = | work = | accessdate = | isbn = 9780781728379 | author1 = Davis, Kenneth L | author2 = Neuropsychopharmacology, American College of | year = 2002 }}</ref><ref>http://www.drugs.com/pro/seroquel.html</ref>


Weight gain can be a problem for some, with quetiapine causing more weight gain than ], ], ], ], ], ], ], ], ], ], and ], but less than ], ], ], and ].<ref name="pmid10553730">{{cite journal | vauthors = Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ | title = Antipsychotic-induced weight gain: a comprehensive research synthesis | journal = The American Journal of Psychiatry | volume = 156 | issue = 11 | pages = 1686–96 | date = November 1999 | pmid = 10553730 | doi = 10.1176/ajp.156.11.1686 | s2cid = 38635470 }}</ref>
* ] (IC<sub>50</sub> = 1268nM), ] (IC<sub>50</sub> = 329nM), ], and ] ]
* ] (IC<sub>50</sub> = 717nM), ], ], and ] ]
* ] (IC<sub>50</sub> = 94nM) and ] (IC<sub>50</sub> = 271nM) ]
* ] (IC<sub>50</sub> = 30nM) ]
* ] (IC<sub>50</sub> = >5000nM) ]


As with some other anti-psychotics, quetiapine may lower the ],<ref>{{cite web | url = http://www.astrazeneca-us.com/cgi-bin/az_pi.cgi?product=seroquel&country=us&popup=no | title = Seroquel Prescribing Information | work = www.astrazeneca-us.com }}</ref> and should be taken with caution in combination with drugs such as ].
This means Quetiapine is a ], ], and ] antagonist, and a potent ] with clinically negligible ] properties. Quetiapine binds strongly to serotonin receptors. Serial PET scans evaluating the D<sub>2</sub> receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D<sub>2</sub> receptor.<ref>{{Cite journal| title =Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?:a new hypothesis.| url = http://ajp.psychiatryonline.org/cgi/content/abstract/158/3/360| pmid =11229973| doi =10.1176/appi.ajp.158.3.360| year =2001| author =Kapur, S.| journal =American Journal of Psychiatry| volume =158| pages =360&ndash;369| last2 =Seeman| first2 =P| issue =3}}</ref> Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the ] and ] pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in ].{{Citation needed|date=November 2007}} Some of the antagonized receptors (serotonin, norepinephrine) are actually ]s whose blockade tends to increase the release of neurotransmitters.


===Discontinuation===
Norquetiapine is the active metabolite of quetiapine. It has most of the effects of quetiapine with similar potencies, and is also a potent ] and ]. Note that the data below is from another source (the official prescribing info for Seroquel), and the measure is different from the above (Ki vs. IC<sub>50</sub>). There are still order-of-magnitude discrepancies for D<sub>1</sub>, &alpha;<sub>1</sub>, H<sub>1</sub> and M<sub>1</sub>.
The ] recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book | editor = Joint Formulary Committee BMJ | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book | vauthors = Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=9780198527480 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |language=en}}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>


There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in reoccurrence of the condition that is being treated.<ref>{{cite book | vauthors = Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=9788847026797 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |language=en}}</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>
<center>

{| class="wikitable"
===Pregnancy and lactation===
|+ Comparison of affinities (Ki, nM)<ref name="dailymed PI">{{cite web |url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=41375#section-15.2 |title=SEROQUEL (quetiapine fumarate) tablet, extended release |author=AstraZeneca Pharmaceuticals LP |year=2011 |month=March |work=DailyMed |publisher=National Library of Medicine |at=Section 12.2: Pharmacodynamics |accessdate=2011-04-26}}</ref>
Placental exposure is least for quetiapine compared to other atypical antipsychotics.<ref name = Maudsley/> The evidence is insufficient to rule out any risk to the foetus but available data suggests it is unlikely to result in any major foetal malformations.<ref name = EMC/><ref name = DM/><ref name = TGA/> It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.<ref name = EMC/><ref name = DM/><ref name = TGA/>
! scope="col" | Receptor

! scope="col" | Quetiapine
===Abuse potential===
! scope="col" | Norquetiapine
In contrast to most other antipsychotic drugs, which tend to be somewhat aversive and often show problems with patient compliance with prescribed medication regimes, quetiapine is sometimes associated with ] and abuse potential, for its hypnotic and sedative effects. It has a limited potential for misuse, usually only in individuals with a history of polysubstance abuse and/or mental illness, and especially in those incarcerated in prisons or secure psychiatric facilities where access to alternative intoxicants is more limited. To a significantly greater extent than other atypical antipsychotic drugs, quetiapine was found to be associated with drug-seeking behaviors, and to have standardised street prices and slang terms associated with it, either by itself or in combination with other drugs (such as "Q-ball" for the intravenous injection of quetiapine mixed with ]). The pharmacological basis for this distinction from other second generation antipsychotic drugs is unclear, though it has been suggested that quetiapine's comparatively lower dopamine receptor affinity and strong antihistamine activity might mean it could be regarded as more similar to sedating ]s in this context. While these issues have not been regarded as sufficient cause for placing quetiapine under increased legal controls, prescribers have been urged to show caution when prescribing quetiapine to individuals with characteristics that might place them at increased risk for drug misuse.<ref>{{cite journal | vauthors = Klein L, Bangh S, Cole JB | title = Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics | journal = The Western Journal of Emergency Medicine | volume = 18 | issue = 2 | pages = 243–250 | date = February 2017 | pmid = 28210359 | pmc = 5305132 | doi = 10.5811/westjem.2016.10.32322 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kim S, Lee G, Kim E, Jung H, Chang J | title = Quetiapine Misuse and Abuse: Is it an Atypical Paradigm of Drug Seeking Behavior? | journal = Journal of Research in Pharmacy Practice | volume = 6 | issue = 1 | pages = 12–15 | year = 2017 | pmid = 28331860 | pmc = 5348850 | doi = 10.4103/2279-042X.200987 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Chiappini S, Schifano F | title = Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of the European Medicines Agency/European Medicines Agency Adverse Drug Reactions' Database | journal = Journal of Clinical Psychopharmacology | volume = 38 | issue = 1 | pages = 72–79 | date = February 2018 | pmid = 29210868 | doi = 10.1097/JCP.0000000000000814 | hdl-access = free | s2cid = 3292900 | hdl = 2299/19835 }}</ref><ref>{{cite journal | vauthors = Evoy KE, Teng C, Encarnacion VG, Frescas B, Hakim J, Saklad S, Frei CR | title = Comparison of Quetiapine Abuse and Misuse Reports to the FDA Adverse Event Reporting System With Other Second-Generation Antipsychotics | journal = Substance Abuse | volume = 13 | pages = 1178221819844205 | year = 2019 | pmid = 31068753 | pmc = 6495438 | doi = 10.1177/1178221819844205 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Vento AE, Kotzalidis GD, Cacciotti M, Papanti GD, Orsolini L, Rapinesi C, Savoja V, Calabrò G, Del Casale A, Piacentino D, Caloro M, Girardi P, Schifano F | title = Quetiapine Abuse Fourteen Years Later: Where Are We Now? A Systematic Review | journal = Substance Use & Misuse | volume = 55 | issue = 2 | pages = 304–313 | year = 2020 | pmid = 31573374 | doi = 10.1080/10826084.2019.1668013 | s2cid = 203621793 }}</ref>

==Overdose==
Most instances of acute overdosage result in only sedation, hypotension and tachycardia, but cardiac arrhythmia, coma and death have occurred in adults. Serum or plasma quetiapine concentrations are usually in the 1–10&nbsp;mg/L range in overdose survivors, while postmortem blood levels of 10–25&nbsp;mg/L are generally observed in fatal cases.<ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1355–1357 }}</ref> Non-toxic levels in postmortem blood extend to around 0.8&nbsp;mg/kg, but toxic levels in postmortem blood can begin at 0.35&nbsp;mg/kg.<ref name="Skov 2015 41-44">{{cite journal | vauthors = Skov L, Johansen SS, Linnet K | title = Postmortem femoral blood reference concentrations of aripiprazole, chlorprothixene, and quetiapine | journal = Journal of Analytical Toxicology | volume = 39 | issue = 1 | pages = 41–44 | date = Jan 2015 | pmid = 25342720 | doi = 10.1093/jat/bku121 | doi-access = free }}</ref><ref name="Skov 2015 557-561">{{cite journal | vauthors = Skov L, Johansen SS, Linnet K | title = Postmortem Quetiapine Reference Concentrations in Brain and Blood | journal = Journal of Analytical Toxicology | volume = 39 | issue = 7 | pages = 557–561 | date = September 2015 | pmid = 26159868 | doi = 10.1093/jat/bkv072 | doi-access = free }}</ref>

==Pharmacology==

===Pharmacodynamics===
{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}
{| class="wikitable floatright" style="font-size:small;"
|+ Quetiapine (and metabolite)<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | website = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://pdsp.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=quetiapine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref><ref name="pmid18059438" />
|- |-
! Site !! {{abbr|QTP|Quetiapine}} !! {{abbr|NQTP|Norquetiapine}} !! Action !! Ref
| D<sub>1</sub> || 428 || 99.8
|- |-
| {{abbrlink|SERT|Serotonin transporter}} || >10,000 || 927 || Blocker || <ref name="pmid18059438">{{cite journal | vauthors = Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL | title = N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity | journal = Neuropsychopharmacology | volume = 33 | issue = 10 | pages = 2303–2312 | date = September 2008 | pmid = 18059438 | doi = 10.1038/sj.npp.1301646 | doi-access = free | author6-link = Bryan Roth }}</ref>
| D<sub>2</sub> || 626 || 489
|- |-
| {{abbrlink|NET|Norepinephrine transporter}} || >10,000 || 58 || Blocker || <ref name="pmid18059438" />
| 5-HT<sub>1A</sub> || 1040 || 191
|- |-
| {{abbrlink|DAT|Dopamine transporter}} || >10,000 || >10,000 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
| 5-HT<sub>2A</sub> || 38 || 2.9
|- |-
| ] || 320–432 || 45 || Partial agonist || <ref name="pmid18059438" /><ref name="pmid8935801">{{cite journal | vauthors = Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE | title = Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding | journal = Psychopharmacology | volume = 124 | issue = 1–2 | pages = 57–73 | date = March 1996 | pmid = 8935801 | doi = 10.1007/bf02245606 | s2cid = 12028979 }}</ref>
| ] || 14.6 || 46.4
|- |-
| ] || 617 || 1290 | ] || 1,109–2,050 || 1,117 || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|- |-
| ] || 4.41 || 1.15 | ] || >10,000 || 249 || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|- |-
| ] || 1086 || 38.3 | ] || 1,250–2,402 || 97 || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|- |-
| ] || 2,240 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || <ref name="pmid8935801" />
| ] || >10000 || 34.8
|-
| ] || 96–101 || 48 || Antagonist || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || {{abbr|ND|No data}} || 14 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 2,502 || 107 || Antagonist || <ref name="pmid18059438" />
|-
| ] || >10,000 || 394 || Antagonist || <ref name="pmid18059438" />
|-
| ] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
| ] || 3,120 || 768 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|-
| ] || 1,865 || 503 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 307 || 76 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 22 || 144 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 39 || 95 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 2,230–3,630 || 237 || Antagonist || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || 90–747 || 378 || Antagonist || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || 28.7–350 || 736 || Antagonist || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || >10,000 || >10,000 || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || >10,000 || >10,000 || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || 712 || 214 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 245 || 196 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 700 || {{abbr|ND|No data}} || Antagonist || <ref name="pmid8935801" />
|-
| ] || 390 || {{abbr|ND|No data}} || Antagonist || <ref name="pmid8935801" />
|-
| ] || 340–483 || 567 || Antagonist || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || 1,202 || 1,297 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 1,600 || {{abbr|ND|No data}} || Antagonist || <ref name="pmid8935801" />
|-
| ] || 1,738 || 1,419 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 2.2–11 || 3.5 || Antagonist || <ref name="pmid18059438" />
|-
| ] || >10,000 || 298 || Antagonist || <ref name="pmid18059438" />
|-
| ] || >10,000 || >10,000 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|-
| ] || >10,000 || 1,660 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|-
| ] || 858 || 39 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 1,339 || 453 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|-
| ] || >10,000 || 23 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 542 || 110 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|-
| ] || 1,942 || 23 || Antagonist || <ref name="pmid18059438" />
|-
| ] || 220–3,651 || >10,000 || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| ] || 1,344 || 1,050 || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|-
| ] || >10,000 || {{abbr|ND|No data}} || Antagonist || <ref name="pmid18059438" />
|-
| {{abbrlink|VDCC|Voltage-dependent calcium channel}} || >10,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || <ref name="pmid18059438" /><ref name="pmid8935801" />
|-
| {{abbrlink|hERG|Human Ether-à-go-go-Related Gene}} || {{abbr|ND|No data}} || >10,000<br />({{abbrlink|IC<sub>50</sub>|Half-maximal inhibitory concentration}}) || {{abbr|ND|No data}} || <ref name="pmid18059438" />
|- class="sortbottom"
| colspan="5" style="width: 1px;" | Values are K<sub>i</sub> (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except σ<sub>1</sub> (guinea pig), σ<sub>2</sub> (rat), and {{abbr|VDCC|Voltage-dependent calcium channel}} (rat).<ref name="pmid18059438" /><ref name="pmid8935801" />
|} |}
</center>


Quetiapine has the following pharmacological actions:<ref name=Seroquel>{{cite web |publisher=] |id=276521 |title=Seroquel (quietapine fumarate) tablets |url=http://www1.astrazeneca-us.com/pi/Seroquel.pdf |url-status = dead|archive-url=https://web.archive.org/web/20080414031803/http://www1.astrazeneca-us.com/pi/Seroquel.pdf |archive-date=14 April 2008 }}</ref><ref name="pmid11132243">{{cite journal | vauthors = Richelson E, Souder T | title = Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds | journal = Life Sciences | volume = 68 | issue = 1 | pages = 29–39 | date = November 2000 | pmid = 11132243 | doi = 10.1016/S0024-3205(00)00911-5 }}</ref><ref name="urlNeuropsychopharmacology: the fifth ... - Google Books">{{cite book | chapter-url = https://books.google.com/books?id=BKwkonZwZD0C&pg=PA778 | vauthors = Miyamoto SE, Duncan GE, Goff DC, Lieberman JA | chapter = Therapeutics of schizophrenia | title = Neuropsychopharmacology: the fifth generation of progress | isbn = 978-0-7817-2837-9 | veditors = Davis KL, Charney D, Coyle JT, Nemeroff C | publisher = American College of Neuropsychopharmacology | year = 2002 }}</ref><ref>{{cite web |url=https://www.drugs.com/pro/seroquel.html |title=Seroquel Official FDA information, side effects and uses |publisher=Drugs.com |access-date=9 July 2012 |url-status = live|archive-url=https://web.archive.org/web/20120604005526/http://www.drugs.com/pro/seroquel.html |archive-date=4 June 2012 }}</ref><ref name="dailymed PI">{{cite web | title=Seroquel- quetiapine tablet, film coated | website=DailyMed | date=27 January 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0584dda8-bc3c-48fe-1a90-79608f78e8a0 | access-date=22 September 2024}}</ref><ref>National Institute of Mental Health. PDSD Ki Database (Internet) . Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: {{cite web|url=http://pdsp.med.unc.edu/pdsp.php |title=...list shows the top 100 Receptors/Targets in Ki|access-date=5 July 2013 |url-status = dead|archive-url=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archive-date=8 November 2013 }}</ref><ref>{{cite journal | vauthors = Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL | title = N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity | journal = Neuropsychopharmacology | volume = 33 | issue = 10 | pages = 2303–2312 | date = September 2008 | pmid = 18059438 | doi = 10.1038/sj.npp.1301646 | doi-access = free }}</ref><ref>{{cite journal | vauthors = López-Muñoz F, Alamo C | title = Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders | journal = Frontiers in Psychiatry | volume = 4 | pages = 102 | date = September 2013 | pmid = 24062697 | pmc = 3770982 | doi = 10.3389/fpsyt.2013.00102 | doi-access = free }}</ref>
==Synthesis==
]


* ] ], ], ], ], and ] ]
Warawa, E. J.; Migler, B. M.; 1988, {{US Patent|4879288}}.
* ] ] ], ], ], ], ], ], and ] ], and ], ], ], and ] ]
* ] and ] ]
* ] ] ]
* ] ]


This means quetiapine is a ], ], and ] antagonist, and a potent ] with some ] properties.<ref>{{cite journal | vauthors = Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, Kirshner MA, Sorisio DA, Bies RR, Gharabawi G | title = Anticholinergic activity of 107 medications commonly used by older adults | journal = Journal of the American Geriatrics Society | volume = 56 | issue = 7 | pages = 1333–1341 | date = July 2008 | pmid = 18510583 | doi = 10.1111/j.1532-5415.2008.01737.x | s2cid = 11448976 }}</ref> Quetiapine binds strongly to serotonin receptors; the drug acts as a ] at 5-HT<sub>1A</sub> receptors and as an antagonist to all other serotonin receptors it has affinity for.<ref>{{cite web | vauthors = Guzman F |title=Mechanism of action of quetiapine |url= http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/mechanism-of-action/|publisher=Psychopharmacology Institute |access-date=20 January 2013 |url-status = live |archive-url= https://web.archive.org/web/20130811004624/http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/mechanism-of-action/ |archive-date=11 August 2013 }}</ref> Serial PET scans evaluating the D<sub>2</sub> receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D<sub>2</sub> receptor.<ref>{{cite journal | vauthors = Kapur S, Seeman P | title = Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis | journal = The American Journal of Psychiatry | volume = 158 | issue = 3 | pages = 360–369 | date = March 2001 | pmid = 11229973 | doi = 10.1176/appi.ajp.158.3.360 }}</ref> Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the ] and ] pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in ].<ref>{{cite journal | vauthors = Seeman P | title = Atypical antipsychotics: mechanism of action | journal = Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie | volume = 47 | issue = 1 | pages = 27–38 | date = February 2002 | pmid = 11873706 | doi = 10.1177/070674370204700106 | doi-access = free }}</ref> Some of the antagonized receptors (serotonin, norepinephrine) are actually ]s whose blockade tends to increase the release of neurotransmitters.
==Dosage==
At very low doses quetiapine acts primarily as a histamine receptor blocker (antihistamine) and ] blocker. When the dose is increased quetiapine activates the adrenergic system and binds strongly to serotonin receptors and ]s. At high doses (over 250&nbsp;mg) quetiapine starts blocking significant amounts of dopamine receptors.<ref>{{cite journal|doi=10.1016/S0024-3205(00)00911-5|title=Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds|journal=Life Sciences|date=November 2000|volume=68|issue=1|pages=29–39|author=E. Richelson and T. Souder|pmid=11132243}}</ref><ref>{{cite journal|doi=10.1016/S0924-977X(00)00133-4|title=D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study|journal=European Neuropsychopharmacology|date=April 2001|volume=11|issue=2|pages=105–110|author=O Gefvert, T Lundberga, I-M Wieselgrenb, M Bergströmc, B Långströmc, F-A Wieselb and L Lindström|pmid=}}</ref> Use of low-dose quetiapine is not recommended except temporarily during drug titration period (less than 30 days).<ref name="low_dose">Oregon State University ''Drug Use Evaluation: Low-Dose Quetiapine (Seroquel, Seroquel XR)'' </ref>


At very low doses, quetiapine acts primarily as a histamine receptor blocker (antihistamine) and ] blocker. When the dose is increased, quetiapine activates the adrenergic system and binds strongly to serotonin receptors and ]s. At high doses, quetiapine starts blocking significant amounts of dopamine receptors.<ref name="pmid11132243"/><ref>{{cite journal | vauthors = Gefvert O, Lundberg T, Wieselgren IM, Bergström M, Långström B, Wiesel F, Lindström L | title = D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study | journal = European Neuropsychopharmacology | volume = 11 | issue = 2 | pages = 105–110 | date = April 2001 | pmid = 11313155 | doi = 10.1016/S0924-977X(00)00133-4 | s2cid = 29460397 }}</ref> Due to the drug's sedating H<sub>1</sub> activity, it is often prescribed at low doses for insomnia. While some feel that low doses of drugs with antihistamine effects like quetiapine and ] are safer than drugs associated with physical dependency or other risk factors, concern has been raised by some professionals that off-label prescribing has become too widespread due to underappreciated hazards.<ref name="low_dose">{{cite web|title=Drug Use Evaluation: Low Dose Quetiapine (Seroquel/Seroquel XR)|url=http://www.govexec.com/pdfs/013111bb1a.pdf|website=Government Executive Media Group|publisher=Oregon State|access-date=20 January 2016|url-status = live|archive-url=https://web.archive.org/web/20160422184014/http://www.govexec.com/pdfs/013111bb1a.pdf|archive-date=22 April 2016}}</ref>
Due to compensatory changes at dopamine, serotonin, adrenergic and histamine receptor sites in the central nervous system, a gradual reduction in dosage is recommended to minimise or avoid withdrawal symptoms. Withdrawal symptoms reported to occur after discontinuation of quetiapine include: ], ], ], ], ], ], ], as well as ], ], ], and ]. The present evidence suggests that these symptoms affect a small number of susceptible individuals treated with quetiapine.<ref name="Kim-2005">{{Cite journal | last1 = Kim | first1 = DR. | last2 = Staab | first2 = JP. | title = Quetiapine discontinuation syndrome. | url = http://ajp.psychiatryonline.org/cgi/content/full/162/5/1020 | journal = Am J Psychiatry | volume = 162 | issue = 5 | pages = 1020 | month = May | year = 2005 | doi = 10.1176/appi.ajp.162.5.1020 | pmid = 15863814 }}</ref> Chronic and long-lasting (months) ] symptoms can occur after discontinuation of quetiapine. {{Citation needed|date=June 2010}}

When treating schizophrenia, antagonism of D<sub>2</sub> receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5-HT<sub>2A</sub> receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes.<ref name="Quetiapine"/><ref name="drugbank.ca">{{cite web |title=Quetiapine |url=https://www.drugbank.ca/drugs/DB01224 |website=www.drugbank.ca |access-date=23 January 2019}}</ref><ref>{{cite web |title=Seroquel |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20639se1-017,016_seroquel_lbl.pdf |website=FDA |access-date=23 January 2019}}</ref> Quetiapine has fewer extrapyramidal side effects and is less likely to cause hyperprolactinemia when compared to other drugs used to treat schizophrenia, so is used as a first line treatment.<ref>{{cite journal | vauthors = Nemeroff CB, Kinkead B, Goldstein J | title = Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing | journal = The Journal of Clinical Psychiatry | volume = 63 | issue = Suppl 13 | pages = 5–11 | date = 2002 | pmid = 12562141 }}</ref><ref>{{cite journal | vauthors = Kasper S, Müller-Spahn F | title = Review of quetiapine and its clinical applications in schizophrenia | journal = Expert Opinion on Pharmacotherapy | volume = 1 | issue = 4 | pages = 783–801 | date = May 2000 | pmid = 11249516 | doi = 10.1517/14656566.1.4.783 | s2cid = 22978385 }}</ref>

===Pharmacokinetics===
Peak levels of quetiapine occur 1.5&nbsp;hours after a dose.<ref name="SeroquelLabel" /> The ] of quetiapine is 83%.<ref name="SeroquelLabel" /> The major ] of quetiapine is ] (''N''-desalkylquetiapine).<ref name="pmid18059438" /> Quetiapine has an ] of 6 or 7&nbsp;hours.<ref name="SeroquelLabel" /><ref name="EMC" /><ref name="DD" /> Its metabolite, norquetiapine, has a half-life of 9 to 12&nbsp;hours.<ref name="EMC" /><ref name="DD" /> Quetiapine is ] primarily via the ]s (73%) and in ] (20%) after hepatic metabolism, the remainder (1%) is excreted as the drug in its unmetabolized form.<ref name="drugbank.ca"/><ref name="SeroquelLabel">{{cite web |title=Seroquel |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/20639se1-017,016_seroquel_lbl.pdf |website=FDA |access-date=23 January 2019}}</ref>

] {{Clear left}}

==Chemistry==
Quetiapine is a ] and is closely related structurally to ], ], ], and other tetracyclic antipsychotics.

===Synthesis===
The synthesis of quetiapine begins with a dibenzothiazepinone. The ] is first treated with ] to produce a ]. A ] is used to introduce the sidechain.<ref>Warawa, E. J.; Migler, B. M.; 1988, {{US Patent|4879288}}.</ref>
{| align="center"
|-
| style="background-color: white !important; color: black !important;" | ]
|}


==History==
The ] recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book |editor1-first=BMJ |editor1-last=Group |title=British National Formulary |edition=57 |year=2009 |month=March |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=0260-535X |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}}</ref>


===Sustained-release=== ===Sustained-release===
AstraZeneca submitted a ] for a ] version of quetiapine in the ], ], and the ] in the second half of 2006 for treatment of ].<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5256.aspx|title=AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR. For the treatment of schizophrenia.|date=2006-07-18|accessdate=2007-01-01}}</ref><ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5275.aspx|title=AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation SEROQUEL XR for the Treatment of Schizophrenia|date=2006-10-19|accessdate=2007-01-01}}</ref> AstraZeneca will retain the exclusive right to market sustained release quetiapine until 2017. The sustained-release quetiapine is marketed mainly as Seroquel XR. Other marketing names are Seroquel Prolong and Seroquel Depot. AstraZeneca submitted a ] for a ] version of quetiapine in the United States, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5256.aspx|title=AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR. For the treatment of schizophrenia.|date=18 July 2006|access-date=1 January 2007|url-status = live|archive-url=https://web.archive.org/web/20061105230337/http://www.astrazeneca.com/pressrelease/5256.aspx|archive-date=5 November 2006}}</ref><ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5275.aspx|title=AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation Seroquel XR for the Treatment of Schizophrenia|date=19 October 2006|access-date=1 January 2007|url-status = live|archive-url=https://web.archive.org/web/20061107132140/http://www.astrazeneca.com/pressrelease/5275.aspx|archive-date=7 November 2006}}</ref>


On May 18, 2007, AstraZeneca announced that the FDA approved Seroquel XR for acute treatment of schizophrenia.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5330.aspx|title=FDA Approves AstraZeneca’s Once-Daily SEROQUEL XR Extended-Release Tablets For The Treatment Of Schizophrenia|date=2007-05-18|accessdate=2007-08-02}}</ref> During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5341.aspx|title=Second Quarter and Half Year Results 2007|date=2007-07-26|accessdate=2007-08-02}}</ref> However, Seroquel XR has only become available in U.S. pharmacies after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on November 16, 2007.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5360.aspx|title=Seroquel XR Receives Approval from FDA for Maintenance Treatment of Schizophrenia|date=2007-11-16|accessdate=2007-12-03}}</ref> The company has not provided a reason for the delay of Seroquel XR's launch. In May 2007, the US FDA approved Seroquel XR for acute treatment of schizophrenia.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5330.aspx|title=FDA Approves AstraZeneca's Once-Daily Seroquel Xr Extended-Release Tablets For The Treatment Of Schizophrenia|date=18 May 2007|access-date=2 August 2007|url-status = live|archive-url=https://web.archive.org/web/20070928040539/http://www.astrazeneca.com/pressrelease/5330.aspx|archive-date=28 September 2007}}</ref> During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5341.aspx|title=Second Quarter and Half Year Results 2007|date=26 July 2007|access-date=2 August 2007|url-status = live|archive-url=https://web.archive.org/web/20070824192553/http://www.astrazeneca.com/pressrelease/5341.aspx|archive-date=24 August 2007}}</ref> However, Seroquel XR has become available in U.S. pharmacies only after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on 16 November 2007.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/pressrelease/5360.aspx|title=Seroquel XR Receives Approval from FDA for Maintenance Treatment of Schizophrenia|date=16 November 2007|access-date=3 December 2007|url-status = live|archive-url=https://web.archive.org/web/20071204160258/http://www.astrazeneca.com/pressrelease/5360.aspx|archive-date=4 December 2007}}</ref> The company has not provided a reason for the delay of Seroquel XR's launch.


] approved sale of Seroquel XR on September 27, 2007.<ref> September 27, 2007, retrieved December 3, 2007</ref> ] approved sale of Seroquel XR on 27 September 2007.<ref>{{dead link|date=July 2016 |bot=InternetArchiveBot |fix-attempted=yes }} 27 September 2007, retrieved 3 December 2007</ref>


The FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania in early October, 2008. According to AstraZeneca, Seroquel XR is "the first medication approved by the FDA for the once-daily acute treatment of both depressive and manic episodes associated with bipolar." In October 2008, the FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania.


In December 2008, ] announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine.<ref>{{cite press release|publisher=]|url=http://www.biovail.com/english/Investor%20Relations/Latest%20News/default.asp?s=1&state=showrelease&releaseid=1230930|title=Biovail Announces Filing of ANDA for Quetiapine XR Tablets|date=1 December 2008|url-status = dead|archive-url=https://web.archive.org/web/20070809023828/http://www.biovail.com/english/investor%20relations/latest%20news/default.asp?s=1|archive-date=9 August 2007}}</ref> Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR.
On July 31, 2008, Handa Pharmaceuticals, based in Fremont, California, announced that its abbreviated new drug application (“ANDA”) for quetiapine fumarate extended-release tablets, the generic version of AstraZeneca’s SEROQUEL XR, has been accepted by the FDA.


On December 1, 2008, ] announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine.<ref>{{cite press release|publisher=]|url=http://www.biovail.com/english/Investor%20Relations/Latest%20News/default.asp?s=1&state=showrelease&releaseid=1230930|title=Biovail Announces Filing of ANDA for Quetiapine XR Tablets|date=2008-12-01|date=2008-12-28}}</ref> Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR. In December 2008, AstraZeneca notified shareholders that the FDA had asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/media/latest-press-releases/seroquel-MDD-FDA-response?itemId=4477598|title=AstraZeneca Receives FDA Complete Response Letter on Seroquel XR for Major Depressive Disorder|date=24 December 2008|access-date=28 December 2008|url-status = live|archive-url=https://web.archive.org/web/20101026190741/http://www.astrazeneca.com/media/latest-press-releases/seroquel-MDD-FDA-response?itemId=4477598|archive-date=26 October 2010}}</ref>


==Society and culture==
On December 24, 2008, AstraZeneca notified shareholders that the FDA had asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression.<ref>{{cite press release|publisher=]|url=http://www.astrazeneca.com/media/latest-press-releases/seroquel-MDD-FDA-response?itemId=4477598|title=AstraZeneca Receives FDA Complete Response Letter on Seroquel XR for Major Depressive Disorder|date=2008-12-24|accessdate=2008-12-28}}</ref>


==Legal status== ===Regulatory status===
In the United States, the ] (FDA) has approved quetiapine for the treatment of ] and of acute ] episodes associated with ] (]) and for treatment of ].<ref name="Off-label">{{cite web | url = http://www.justice.gov/opa/pr/2010/April/10-civ-487.html | title = Pharmaceutical Giant AstraZeneca to Pay $520 Million for Off-label Drug Marketing | publisher = Justice news, US Department of Justice | access-date = 16 July 2012 |url-status = live| archive-url = https://web.archive.org/web/20120713201923/http://www.justice.gov/opa/pr/2010/April/10-civ-487.html | archive-date = 13 July 2012 | date = 27 April 2010 }}</ref> In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.<ref>{{cite web| vauthors = Guzman F |title=Quetiapine Indications: FDA-Approved and Off-label Uses |url= http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/quetiapine-indications/|publisher=Psychopharmacology Institute |access-date=19 January 2013 |url-status = live |archive-url= https://web.archive.org/web/20140122132819/http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/quetiapine-indications/ |archive-date=22 January 2014 }}</ref>
Quetiapine received its initial indication from the ] for treatment of ] in 1997.<ref>{{cite web|title=QUETIAPINE FUMARATE|work=Electronic Orange Book|publisher=Food and Drug Administration|date=April 2007|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020639&TABLE1=OB_Rx|accessdate=2007-05-24}}</ref> In 2004, it received its second indication for the treatment of mania-associated ].<ref>{{cite press release| publisher=]|date=2004-01-13
| title = AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania
| url = http://www.prnewswire.co.uk/cgi/news/release?id=115109
}}</ref> In 2007 and 2008, studies were conducted on quetiapine’s efficacy in treating generalized anxiety disorder and major depression. In April 2009, the Psychopharmacologic Drugs Advisory Committee of the US ] (FDA) held a public meeting to discuss whether study results supported the FDA's approval for anxiety and depression, with risks of metabolic side-effects and of tardive dyskinesia and sudden cardiac death.<ref>{{cite web| title = April 7–8, 2009: Psychopharmacologic Drugs Advisory Committee Meeting Announcement| url = http://www.fda.gov/AdvisoryCommittees/Calendar/ucm136250.htm| accessdate = 2009-08-27}}</ref>


Quetiapine received its initial approval from the US FDA for the treatment of schizophrenia in 1997.<ref name="dailymed PI" /><ref>{{cite web|title=QUETIAPINE FUMARATE|website=Electronic Orange Book|publisher=Food and Drug Administration|date=April 2007|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020639&TABLE1=OB_Rx|access-date=24 May 2007|url-status = live|archive-url=https://web.archive.org/web/20090105000412/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020639&TABLE1=OB_Rx|archive-date=5 January 2009}}</ref> In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.<ref>{{cite press release| publisher=]| date=13 January 2004| title=AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania| url=http://www.prnewswire.co.uk/cgi/news/release?id=115109 |url-status = live| archive-url= https://web.archive.org/web/20110608181218/http://www.prnewswire.co.uk/cgi/news/release?id=115109| archive-date=8 June 2011}}</ref> In 2007 and 2008, studies were conducted on quetiapine's efficacy in treating generalized anxiety disorder and major depression.
==Controversy==
AstraZeneca has been sued by the U.S. government over the marketing of quetiapine. A $520 million settlement was reached on October 29, 2009.<ref>{{Cite news|last = Wilson | first = Duff | title = AstraZeneca Pays Millions to Settle Seroquel Cases | newspaper = New York Times | date = 2009-10-29 | url = http://www.nytimes.com/2009/10/30/business/30drug.html | accessdate = 2010-03-09}}</ref>


Patent protection for the product ended in 2012; however, in a number of regions, the long-acting version remained under patent until 2017.<ref>{{cite web|author1=AstraZeneca|title=Pioneering science, life-changing medicines |url= https://www.sec.gov/Archives/edgar/data/901832/000095010314001994/dp44853_ex1501.htm |website=www.sec.gov| access-date=26 March 2017|date=2013|url-status = live |archive-url=https://web.archive.org/web/20160306213537/http://www.sec.gov/Archives/edgar/data/901832/000095010314001994/dp44853_ex1501.htm |archive-date=6 March 2016 }}</ref>
Several American soldiers and veterans have died while taking Seroquel for ].<ref>{{cite news| title= Questions loom over drug given to sleepless vets| author= Matthew Perrone| newspaper= Associate Press| date= August 30, 2010| url= http://health.yahoo.net/news/s/ap/us_veterans_sleep_drug| accessdate=November 28, 2010}}</ref>


===Lawsuits===
Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, ].<ref>{{Cite news| url=http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research| title=Seroquel suit claims 'so much' is poured into marketing and away from research| work=]| author=Ann Knef| date=2007-08-02}}</ref><ref name="BloombergNewsSeroquelDiabetes">{{cite news| author=Phil Milford| date=2009-03-11| work=Bloomberg.com| publisher=]| url=http://www.bloomberg.com/apps/news?pid=newsarchive&sid=ayzJsK2HlF6s| title=AstraZeneca May Link Seroquel, Diabetes, Doctor Says}}</ref><ref>http://www.fiercepharma.com/story/astrazeneca-wins-bellwether-seroquel-case/2010-03-19</ref><ref>{{Cite news| url=http://www.thelocal.se/28260/20100809/| title=AstraZeneca pays out million dollar damages| work=]| date=2010-08-09}}</ref>
In April 2010, the U. S. Department of Justice fined AstraZeneca $520 million for the company's aggressive marketing of Seroquel for ]s.<ref name="Off-label"/> According to the Department of Justice, "the company recruited doctors to serve as authors of articles that were ghostwritten by medical literature companies and about studies the doctors in question did not conduct. AstraZeneca then used those studies and articles as the basis for promotional messages about unapproved uses of Seroquel."<ref name="Off-label"/>


Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, ].<ref>{{cite news| url=http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research| title=Seroquel suit claims 'so much' is poured into marketing and away from research| work=]| vauthors = Knef A | date=2 August 2007|url-status = live| archive-url=https://web.archive.org/web/20080821141631/http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research| archive-date=21 August 2008}}</ref><ref name="BloombergNewsSeroquelDiabetes">{{cite news| vauthors = Milford P | date=11 March 2009| work=Bloomberg.com| publisher=]| url=https://www.bloomberg.com/apps/news?pid=newsarchive&sid=ayzJsK2HlF6s| title=AstraZeneca May Link Seroquel, Diabetes, Doctor Says|url-status = live| archive-url=https://web.archive.org/web/20150924191537/http://www.bloomberg.com/apps/news?pid=newsarchive&sid=ayzJsK2HlF6s| archive-date=24 September 2015}}</ref><ref>{{cite web |url=http://www.fiercepharma.com/story/astrazeneca-wins-bellwether-seroquel-case/2010-03-19 |title=AstraZeneca wins bellwether Seroquel case |publisher=FiercePharma |date=19 March 2010 |access-date=9 July 2012 |url-status = live|archive-url=https://web.archive.org/web/20120314034519/http://www.fiercepharma.com/story/astrazeneca-wins-bellwether-seroquel-case/2010-03-19 |archive-date=14 March 2012 }}</ref><ref>{{cite news|url=http://www.thelocal.se/28260/20100809/|title=AstraZeneca pays out million dollar damages|work=]|date=9 August 2010|url-status = live|archive-url=https://web.archive.org/web/20100817204556/http://www.thelocal.se/28260/20100809/|archive-date=17 August 2010}}</ref>
==Recreational use==

Quetiapine is not classified as a controlled substance, "abusive self-administration seems to be driven by quetiapine’s sedative and ] effects (to help with sleep or to 'calm down') rather than by its antipsychotic properties."<ref>{{cite web|title=Intranasal Quetiapine Abuse|author=Joseph M. Pierre, M.D., Igor Shnayder, M.D., Donna A. Wirshing, M.D., and William C. Wirshing, M.D.|url=http://ajp.psychiatryonline.org/cgi/content/full/161/9/1718|publisher=American Psychiatric Association}}</ref> Reports of quetiapine abuse have emerged in the medical literature, however, while the drug is usually abused through the crushing and snorting of tablets (]), there have also been reports of intravenous abuse and intravenous co-administration with ].<ref name="Brian M. Waters and Kaustubh G. Joshi 173-a-174">{{cite journal|journal=Am J Psychiatry|volume=164|issue=1|pages=173-a-174|date=January 2007|pmid=17202567|doi=10.1176/appi.ajp.164.1.173-a|url=http://ajp.psychiatryonline.org/cgi/content/full/164/1/173-a|title=Intravenous Quetiapine-Cocaine Use ("Q-Ball")|publisher=]|author=Brian M. Waters and Kaustubh G. Joshi|work=Letters to the Editor}}</ref> This is commonly referred to as a "Q-Ball".<ref name="Brian M. Waters and Kaustubh G. Joshi 173-a-174"/> A 2004 letter to the editor of the American Journal of Psychiatry provided an anecdotal estimate that up to 30% of inmates who were seen for psychiatric services in the Los Angeles County Jail were faking psychotic symptoms in an attempt to obtain quetiapine.<ref>{{cite journal|journal=Am J Psychiatry|volume=161|issue=9|pages=1718|date=September 2004|url=http://ajp.psychiatryonline.org/cgi/content/full/161/9/1718|title=Intranasal Quetiapine Abuse|pmid=15337673|publisher=]|author=Joseph M. Pierre, Igor Shnayder, Donna A. Wirshing, and William Wirshing|work=Letters to the Editor|doi=10.1176/appi.ajp.161.9.1718}}</ref> Also known as "quell", "Snoozeberries", or "]", the drug may be more commonly abused in prisons due to its capacity to be regularly prescribed as a sedative and the unavailability in prison of more commonly abused substances. A letter to the editor that appeared in the January 2007 ''American Journal of Psychiatry'' has proposed a “need for additional studies to explore the addiction-potential of quetiapine”. The letter reports that its authors are physicians who work in the Ohio correctional system. They report that “prisoners ... have threatened legal action and even ] when presented with discontinuation of quetiapine” and that they have “not seen similar drug-seeking behavior with other second-generation antipsychotics of comparable efficacy”. It has also been reported that when Seroquel is used with ] it causes the user to experience a buzz, or opioid euphoria.<ref name="Pinta Taylor : Quetiapine Addiction?">{{cite doi|10.1176/appi.ajp.164.1.174}}</ref>
Approximately 10,000<ref>{{cite news |url=http://www.marinecorpstimes.com/news/2010/08/ap-veterans-affairs-investigation-into-seroquel-083010/ |title=Questions loom over drug for sleepless vets - Marine Corps News &#124; News from Afghanistan & Iraq |newspaper=] |access-date=9 July 2012 |url-status = dead|archive-url=https://web.archive.org/web/20130602184342/http://www.marinecorpstimes.com/news/2010/08/ap-veterans-affairs-investigation-into-seroquel-083010/ |archive-date=2 June 2013 }}</ref> lawsuits<ref>{{cite web | vauthors= Wilson D |url=https://www.nytimes.com/2011/07/19/health/19drug.html?_r=2 |title=Heart Warning Added to Label on Popular Antipsychotic Drug |publisher=NyTimes |date=19 July 2011 |access-date=9 July 2012 |url-status = live|archive-url=https://web.archive.org/web/20120702172131/http://www.nytimes.com/2011/07/19/health/19drug.html?_r=2 |archive-date=2 July 2012 }}</ref> have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths.

===Controversy===
In 2004, a young man named ] committed suicide in a controversial Seroquel clinical trial at the University of Minnesota while under an involuntary commitment order.<ref>{{cite news | vauthors = Elliott C |title=The Deadly Corruption of Clinical Trials|url=https://www.motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca|access-date=2 December 2012|newspaper=Mother Jones|date=September–October 2010|url-status = live|archive-url=https://web.archive.org/web/20121117015108/https://www.motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca|archive-date=17 November 2012}}</ref> A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations.<ref>{{cite news| vauthors = Couzin-Frankel J |title=Minnesota bioethicists critique their university|url=http://news.sciencemag.org/scienceinsider/2010/12/minnesota-bioethicists-critique-.html|access-date=2 December 2012|newspaper=Science|date=7 December 2010|url-status = dead|archive-url=https://web.archive.org/web/20130221014413/http://news.sciencemag.org/scienceinsider/2010/12/minnesota-bioethicists-critique-.html|archive-date=21 February 2013}}</ref>

===Nurofen Plus tampering case===
In August 2011, the UK's ] (MHRA) issued a class-4 drug alert following reports that some batches of ] contained Seroquel XL tablets instead.<ref>{{cite press release |url=http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON126226 |title=Press release, 25 August 2011 |publisher=MHRA |access-date=9 July 2012 |url-status = dead |archive-url=https://web.archive.org/web/20120319232125/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON126226 |archive-date=19 March 2012 }}</ref>

Following the issue of the Class-4 Drug Alert, Reckitt Benckiser (UK) Ltd received further reports of rogue blister strips in cartons of two additional batches of Nurofen Plus tablets. One of the new batches contained Seroquel XL 50&nbsp;mg tablets and one contained the Pfizer product ] 100&nbsp;mg capsules.

Following discussions with the MHRA's Defective Medicines Report Centre (DMRC), Reckitt Benckiser (UK) Ltd decided to recall all remaining unexpired stock of Nurofen Plus tablets in any pack size, leading to a Class-1 Drug Alert.<ref>{{cite web |url=http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON126268 |title=Drug Alerts |publisher=MHRA |access-date=9 July 2012 |url-status = live|archive-url=https://web.archive.org/web/20120319232133/http://www.mhra.gov.uk/Publications/Safetywarnings/DrugAlerts/CON126268 |archive-date=19 March 2012 }}</ref> The contamination was later traced to in-store tampering by a customer.<ref>{{cite web |url=https://www.bbc.co.uk/news/uk-england-london-18203634 |title=Nurofen Plus tampering: Christopher McGuire jailed |publisher=] |date=28 May 2012 |access-date=9 July 2012 |url-status = live|archive-url=https://web.archive.org/web/20120614124729/http://www.bbc.co.uk/news/uk-england-london-18203634 |archive-date=14 June 2012 }}</ref>


== References == == References ==
{{Reflist}}
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== External links == == External links ==
{{Commons category}}
* {{cite web|publisher=The American Society of Health-System Pharmacists, Inc.|work=]|title=Quetiapine|date=2008-09-01|url=http://nlm.nih.gov/medlineplus/druginfo/meds/a698019.html}}
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