Quetiapine

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Quetiapine is primarily used to treat schizophrenia or bipolar disorder.{{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}} Quetiapine targets both positive and negative symptoms of schizophrenia.{{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 }}

A 2013 Cochrane review compared quetiapine to typical antipsychotics:

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In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13–16% more effective than ziprasidone, chlorpromazine, and asenapine and approximately as effective as haloperidol and aripiprazole.

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.{{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 }}

It is debatable whether, as a class, typical or atypical antipsychotics are more effective.{{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 }} Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages.{{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 }} While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.

A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than olanzapine and risperidone; produce fewer movement related side effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine; and produce weight gain similar to risperidone, clozapine and aripiprazole. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity and decline in white blood cell count at a rate similar to first generation antipsychotics.{{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 }}

In those with bipolar disorder, quetiapine is used to treat depressive episodes; acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium; valproate or lamotrigine); acute mixed episodes; and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).

Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD).{{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 }} However, sedation is often an undesirable side effect.

In the United States, the United Kingdom and Australia (while not subsidised by the Australian Pharmaceutical Benefits Scheme for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD.{{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 }}

Quetiapine does not decrease agitation among people with Alzheimer's disease. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.{{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 }}

The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.{{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 }}{{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 }}{{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 }}{{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 }}{{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}}{{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 }} 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 effect size (standardized mean difference) against placebo 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 certainty of evidence rated as very low.{{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 }} 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.{{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 }} Regardless of the dose used, some of the more serious adverse effects may still possibly occur at the lower dosing ranges, such as dyslipidemia and neutropenia.{{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 }}{{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 }} 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 Z-drugs, with most of the risk being driven by cardiovascular death.{{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 }} 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.{{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}}

It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,{{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 }} musical hallucinationsOliver Sacks "Musicophilia" Knopf NY 2007 P.67 and anxiety 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 }}

Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their relatively low extrapyramidal side-effect liability.{{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. ... 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 }} 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.{{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 }}

Sources for incidence lists:{{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}}{{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}}{{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}}

;Very common (>10% incidence) adverse effects

• Dry mouth
• Dizziness
• Headache
• Somnolence (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.){{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 }}

;Common (1–10% incidence) adverse effects

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• High blood pressure
• Orthostatic hypotension
• High pulse rate
• High blood cholesterol
• Elevated serum triglycerides
• Abdominal pain
• Constipation
• Increased appetite
• Vomiting
• Increased liver enzymes
• Backache
• Asthenia
• Insomnia
• Lethargy
• Tremor
• Agitation
• Nasal congestion
• Pharyngitis
• Fatigue
• Pain
• Dyspepsia (Indigestion)
• Peripheral oedema
• Dysphagia

{{colend}}

• Extrapyramidal disease: Quetiapine and clozapine are noted for their relative lack of extrapyramidal side effects.
• Weight gain: SMD 0.43 kg when compared to placebo. Produces roughly as much weight gain as risperidone, less weight gain than clozapine, olanzapine and zotepine and more weight gain than ziprasidone, lurasidone, aripiprazole and asenapine. As with many other atypical antipsychotics, this action is likely due to its actions at the H₁ histamine receptor and 5-HT_2C receptor.

;Rare (<1% incidence) adverse effects

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• Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17)
• Sudden cardiac death
• Syncope
• Diabetic ketoacidosis
• Restless legs syndrome
• Hyponatraemia, low blood sodium.
• Jaundice, 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.
• Pancreatitis, pancreas swelling.
• Agranulocytosis, a potentially fatal drop in white blood cell count.
• Leukopenia, a drop in white blood cell count, not as severe as agranulocytosis.
• Neutropenia, a drop in neutrophils, the cell of the immune cells that defends the body against bacterial infections.
• Eosinophilia
• Anaphylaxis, a potentially fatal allergic reaction.
• Seizure
• Hypothyroidism, underactive thyroid gland. Common among bipolar patients; quetiapine increases incidence.{{cite journal | vauthors = Lambert CG, Mazurie AJ, Lauve NR, Hurwitz NG, Young SS, Obenchain RL, Hengartner NW, Perkins DJ, Tohen M, Kerner B | title = Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort | journal = Bipolar Disorders | volume = 18 | issue = 3 | pages = 247–260 | date = May 2016 | pmid = 27226264 | pmc = 5089566 | doi = 10.1111/bdi.12391 }}
• Myocarditis, swelling of the myocardium.
• Cardiomyopathy
• Hepatitis, swelling of the liver.
• Suicidal ideation
• Priapism. A prolonged and painful erection.
• Stevens–Johnson syndrome. A potentially fatal skin reaction.

{{colend}}

• Neuroleptic malignant syndrome 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.
• Tardive dyskinesia. 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

Both typical and atypical antipsychotics can cause tardive dyskinesia.{{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 }} According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%. Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.{{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 }}

Weight gain can be a problem for some, with quetiapine causing more weight gain than fluphenazine, haloperidol, loxapine, molindone, olanzapine, pimozide, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone, but less than chlorpromazine, clozapine, perphenazine, and sertindole.{{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 }}

As with some other anti-psychotics, quetiapine may lower the seizure threshold,{{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 }} and should be taken with caution in combination with drugs such as bupropion.

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.{{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.}} Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.{{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}} Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.{{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 }} It may also result in reoccurrence of the condition that is being treated.{{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}} Rarely tardive dyskinesia can occur when the medication is stopped.

Placental exposure is least for quetiapine compared to other atypical antipsychotics. 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. It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.

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 drug misuse 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 cocaine). 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 antihistamines 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.{{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 }}{{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 }}{{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 }}{{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 }}{{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 }}

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 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases.{{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 }} Non-toxic levels in postmortem blood extend to around 0.8 mg/kg, but toxic levels in postmortem blood can begin at 0.35 mg/kg.{{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 }}{{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 }}

{{See also|Atypical antipsychotic#Pharmacodynamics|Antipsychotic#Comparison of medications}}

Quetiapine has the following pharmacological actions:{{cite web |publisher=AstraZeneca |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 }}{{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 }}{{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 }}{{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 }}{{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}}National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Sep 18]. 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 }}{{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 }}{{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 }}

• Dopamine D₁, D₂, D₃, D₄, and D₅ receptor antagonist
• Serotonin 5-HT_1A receptor partial agonist, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₃, 5-HT₆, and 5-HT₇ receptor antagonist, and 5-HT_1B, 5-HT_1D, 5-HT_1E, and 5-HT_1F receptor ligand
• α₁- and α₂-adrenergic receptor antagonist
• Histamine H₁ receptor antagonist
• Muscarinic acetylcholine receptor antagonist

This means quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties.{{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 }} Quetiapine binds strongly to serotonin receptors; the drug acts as a partial agonist at 5-HT_1A receptors and as an antagonist to all other serotonin receptors it has affinity for.{{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 }} Serial PET scans evaluating the D₂ receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D₂ receptor.{{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 }} Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in prolactin.{{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 }} Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters.

At very low doses, quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α₁-adrenergic blocker. When the dose is increased, quetiapine activates the adrenergic system and binds strongly to serotonin receptors and autoreceptors. At high doses, quetiapine starts blocking significant amounts of dopamine receptors.{{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 }} Due to the drug's sedating H₁ activity, it is often prescribed at low doses for insomnia. While some feel that low doses of drugs with antihistamine effects like quetiapine and mirtazapine 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.{{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}}

When treating schizophrenia, antagonism of D₂ receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5-HT_2A receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes.{{cite web |title=Quetiapine |url=https://www.drugbank.ca/drugs/DB01224 |website=www.drugbank.ca |access-date=23 January 2019}}{{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}} 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.{{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 }}{{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 }}

Peak levels of quetiapine occur 1.5 hours after a dose. The plasma protein binding of quetiapine is 83%. The major active metabolite of quetiapine is norquetiapine (N-desalkylquetiapine). Quetiapine has an elimination half-life of 6 or 7 hours. Its metabolite, norquetiapine, has a half-life of 9 to 12 hours. Quetiapine is excreted primarily via the kidneys (73%) and in feces (20%) after hepatic metabolism, the remainder (1%) is excreted as the drug in its unmetabolized form.{{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}}

File:Norquetiapine.svg {{Clear left}}

Quetiapine is a tetracyclic compound and is closely related structurally to clozapine, olanzapine, loxapine, and other tetracyclic antipsychotics.

The synthesis of quetiapine begins with a dibenzothiazepinone. The lactam is first treated with phosphoryl chloride to produce a dibenzothiazepine. A nucleophilic substitution is used to introduce the sidechain.Warawa, E. J.; Migler, B. M.; 1988, {{US Patent|4879288}}.

File:Quetiapine syn.png

AstraZeneca submitted a new drug application for a sustained-release version of quetiapine in the United States, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia.{{cite press release|publisher=AstraZeneca|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}}{{cite press release|publisher=AstraZeneca|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}}

In May 2007, the US FDA approved Seroquel XR for acute treatment of schizophrenia.{{cite press release|publisher=AstraZeneca|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}} During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.{{cite press release|publisher=AstraZeneca|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}} 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.{{cite press release|publisher=AstraZeneca|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}} The company has not provided a reason for the delay of Seroquel XR's launch.

Health Canada approved sale of Seroquel XR on 27 September 2007.[http://cpe0013211b4c6d-cm0014e88ee7a4.cpe.net.cable.rogers.com/NocWeb/viewnoce.jsp?noc=kilh Notice of Compliance Information - Seroquel XR]{{dead link|date=July 2016 |bot=InternetArchiveBot |fix-attempted=yes }} 27 September 2007, retrieved 3 December 2007

In October 2008, the FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania.

In December 2008, Biovail announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine.{{cite press release|publisher=Biovail|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}} 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.{{cite press release|publisher=AstraZeneca|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}}

In the United States, the Food and Drug Administration (FDA) has approved quetiapine for the treatment of schizophrenia and of acute manic episodes associated with bipolar disorder (bipolar mania) and for treatment of bipolar depression.{{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 }} In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.{{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 }}

Quetiapine received its initial approval from the US FDA for the treatment of schizophrenia in 1997.{{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}} In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.{{cite press release| publisher=AstraZeneca| 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}} In 2007 and 2008, studies were conducted on quetiapine's efficacy in treating generalized anxiety disorder and major depression.

Patent protection for the product ended in 2012; however, in a number of regions, the long-acting version remained under patent until 2017.{{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 }}

In April 2010, the U. S. Department of Justice fined AstraZeneca $520 million for the company's aggressive marketing of Seroquel for off-label uses. 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."

Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, diabetes.{{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=The Madison / St. Clair Record| 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}}{{cite news| vauthors = Milford P | date=11 March 2009| work=Bloomberg.com| publisher=Bloomberg L.P.| 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}}{{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 }}{{cite news|url=http://www.thelocal.se/28260/20100809/|title=AstraZeneca pays out million dollar damages|work=The Local|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}}

Approximately 10,000{{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 | News from Afghanistan & Iraq |newspaper=Marine Corps Times |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 }} lawsuits{{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 }} have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths.

In 2004, a young man named Dan Markingson committed suicide in a controversial Seroquel clinical trial at the University of Minnesota while under an involuntary commitment order.{{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}} A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations.{{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}}

In August 2011, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a class-4 drug alert following reports that some batches of Nurofen plus contained Seroquel XL tablets instead.{{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 }}

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 mg tablets and one contained the Pfizer product Neurontin 100 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.{{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 }} The contamination was later traced to in-store tampering by a customer.{{cite web |url=https://www.bbc.co.uk/news/uk-england-london-18203634 |title=Nurofen Plus tampering: Christopher McGuire jailed |publisher=BBC News |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 }}

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