|Systematic (IUPAC) name|
|2-(2-(4-dibenzo[b,f][1,4]thiazepine- 11-yl- 1-piperazinyl)ethoxy)ethanol|
|Licence data||US FDA:|
|Pregnancy cat.||B3 (AU) C (US)|
|Legal status||Prescription Only (S4) (AU) POM (UK) ℞-only (US)|
|Metabolism||Hepatic via CYP3A4-catalysed sulfoxidation to its active metabolite norquetiapine (N-desalkylquetiapine)|
|Half-life||7 hours (parent compound); 9-12 hours (active metabolite, norquetiapine)|
|Excretion||Renal (73%), faeces (20%)|
|Mol. mass||383.5099 g/mol|
|Solubility in water||3.29 mg/mL (20 °C)|
|(what is this?)|
Quetiapine (// kwi-TY-ə-peen) (branded as Seroquel, Xeroquel, Ketipinor; Hedonin by G.L. Pharma) is a short-acting atypical antipsychotic approved for the treatment of schizophrenia, bipolar disorder, and along with an antidepressant to treat major depressive disorder.
Annual sales are approximately $5.7 billion worldwide, with $2.9 billion in the United States. The U.S. patent, which was set to expire in 2011, received a pediatric exclusivity extension which pushed its expiration to March 26, 2012. The patent has already expired in Canada. Quetiapine was developed by AstraZeneca from 1992-1996 as an improvement from first generation antipsychotics. It was first approved by the FDA in 1997. There are now several generic versions of quetiapine, such as Quepin, Syquel and Ketipinor.
- 1 Medical uses
- 2 Adverse effects
- 3 Pharmacology
- 4 Synthesis
- 5 Dosage
- 6 Society and culture
- 7 References
- 8 External links
Quetiapine fumarate is primarily used to treat schizophrenia or bipolar disorder.
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.
It is debatable whether, as a class, typical or atypical antipsychotics are more effective. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.
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), and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).
Major depressive disorder
Quetiapine does not decrease agitation among people with Alzheimer's, whose usage of the drug once constituted 29% of sales. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.
Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their very low extrapyramidal side effect liability. 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.
- Very common (>10% incidence) adverse effects
- Dry mouth
- 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)
- Common (1-10% incidence) adverse effects
- High blood pressure
- Orthostatic hypotension
- High pulse rate
- High blood cholesterol
- Elevated serum triglycerides
- Abdominal pain
- Increased appetite
- Increased liver enzymes
- Nasal congestion
- Dyspepsia (Indigestion)
- Peripheral oedema
- 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-HT2C receptor.
- Rare (<1% incidence) adverse effects
- Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17)
- Sudden cardiac death
- 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.
- Anaphylaxis, a potentially fatal allergic reaction.
- Hypothyroidism, underactive thyroid gland.
- Myocarditis, swelling of the myocardium.
- Hepatitis, swelling of the liver.
- Suicidal ideation
- Priapism. A prolonged and painful erection.
- Stevens-Johnson syndrome. A potentially fatal skin reaction.
- 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
There is an emerging controversy regarding quetiapine fatalities. The deaths of at least six U.S. military veterans who were given drug cocktails including quetiapine have been attributed to its inclusion by military doctors to treat PTSD. Approximately 10,000 lawsuits against AstraZeneca for problems ranging from slurred speech and chronic insomnia to death have been filed by individuals from civilian populations.
It is marketed as one of the most sedating of all anti-psychotics, although those claims are contested. Beginning users may feel extremely tired and 'out of it' for the first few days, and sometimes longer. Quetiapine's newest indication, for bipolar 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.
Both typical and atypical antipsychotics can cause tardive dyskinesia. 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.
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.
Studies conducted on beagles have resulted in the formation of cataracts. 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. However, the Seroquel website still recommends users have eye examinations every six months.
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 (but still better than no anti-psychotics drug treatment at all).
Quetiapine should be discontinued gradually, with careful consideration from the prescribing doctor, to avoid withdrawal symptoms or relapse.
The British National Formulary recommends a gradual withdrawal when discontinuing anti-psychotic treatment to avoid acute withdrawal syndrome or rapid relapse. 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. However, despite increasing demand for safe and effective antipsychotic withdrawal protocols or dose-reduction schedules, no specific guidelines with proven safety and efficacy are currently available.
Withdrawal symptoms reported to occur after discontinuation of antipsychotics include nausea, emesis, lightheadedness, diaphoresis, dyskinesia, orthostatic hypotension, tachycardia, insomnia, nervousness, dizziness, headache, excessive non-stop crying, and anxiety. According to Eli Lilly internal documents, discontinuation of atypical neuroleptics similar to seroquel can also cause psoriasis, gingivitis and other inflammatory conditions, dyspepsia, headache, high blood sugar and other health conditions unrelated to psychiatric condition. Some have argued that additional somatic and psychiatric symptoms associated with dopaminergic super-sensitivity, including dyskinesia and acute psychosis, are common features of withdrawal in individuals treated with neuroleptics. This has led some to suggest that the withdrawal process might itself be psychosis-mimetic, producing psychotic-like symptoms even in previously healthy patients, indicating a possible pharmacological origin of mental illness in a yet unknown percentage of patients currently and previously treated with antipsychotics. This question is unresolved, and remains a highly controversial issue among professionals in the medical and mental health communities, as well the public.
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 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases.
Pregnancy and lactation
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.
|Receptor||Quetiapine (Cloned human receptors)||Norquetiapine (Cloned human receptors)|
|D1||994.5||99.8 (Rat receptor)|
|α1B||14.6||46.4 (Rat receptor)|
|M1||489||38.3 (Rat receptor)|
- D1 (IC50 = 1268nM), D2 (IC50 = 329nM), D3, and D4 receptor antagonist
- 5-HT1A (IC50 = 717nM) partial agonist, 5-HT2A (IC50 = 148nM), 5-HT2C, and 5-HT7 receptor antagonist
- α1-adrenergic (IC50 = 94nM) and α2-adrenergic receptor (IC50 = 271nM) antagonist
- H1 receptor (IC50 = 30nM) antagonist
- mACh receptor (IC50 = >5000nM) antagonist
This means Quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with clinically negligible anticholinergic properties. Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. 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. Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters.
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.
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. Use of low-dose quetiapine is not recommended except temporarily during drug titration period (less than 30 days).
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 insomnia, nausea, emesis, lightheadedness, diaphoresis, orthostatic hypotension, tachycardia, as well as nervousness, dizziness, headache, and anxiety. The present evidence suggests that these symptoms affect a small number of susceptible individuals treated with quetiapine.
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. 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, Seroquel Depot and Seroquel XL
On May 18, 2007, AstraZeneca announced that the U.S. FDA approved Seroquel XR for acute treatment of schizophrenia. During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during 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 November 16, 2007. The company has not provided a reason for the delay of Seroquel XR's launch.
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."
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, Biovail announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine. Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR.
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.
Society and culture
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. In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.
Quetiapine received its initial indication from U.S. FDA for treatment of schizophrenia in 1997. In 2004, it received its second indication for the treatment of mania-associated bipolar disorder. 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 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.
In April 2010, AstraZeneca settled a longstanding U. S. Department of Justice investigation into its aggressive marketing of Seroquel for such off-label uses with a $520-million fine. 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. In 2009, documents unsealed in litigation against AstraZeneca indicated that Dr. Charles Schulz, Chair of the Department of Psychiatry at the University of Minnesota and a consultant for AstraZeneca, had misrepresented the benefits of Seroquel in research presentations and press releases.
AstraZeneca has been sued by the U.S. government (resulting from a qui tam lawsuit filed by Stefan P. Kruszewski) over the marketing of quetiapine. A $520-million settlement was reached on October 29, 2009.
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. A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations, but the university declined to investigate. Quetiapine may have been a factor in the deaths of several US veterans who were taking large doses as part of a cocktail of drugs for PTSD.[relevant? ]
In Australia, Professor Patrick McGorry, a key mental-health advisor, proposed a trial in Melbourne in 2011. Its purpose was to investigate whether Seroquel would decrease or delay the risk that people aged between 15 and 40 with early signs of mental illness, might develop a later psychotic disorder. However in July 2011, psychiatrists, psychologists and researchers from Australia, New Zealand, Canada, Britain and the US lodged a complaint with the ethics committee of Melbourne Health. They opposed the trial as "unethical" and "dangerous".
Quetiapine is not classified as a controlled substance; "abusive self-administration seems to be driven by quetiapine’s sedative and anxiolytic effects (to help with sleep or to 'calm down') rather than by its antipsychotic properties." Reports of quetiapine abuse have emerged in medical literature. In addition to oral administration, the drug is also taken intranasally by snorting pulverized tablets (insufflation). There have been reports of intravenous abuse and intravenous co-administration with cocaine as well. This is commonly referred to as a "Q-Ball". 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. Also known as "quell", "Snoozeberries", or "Susie-Q", 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 suicide 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 methadone, it causes the user to experience a buzz, or opioid euphoria.
Nurofen Plus tampering case
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 instead.
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. The contamination was later traced to in-store tampering by a customer.
- "quetiapine (Rx) - Seroquel, Seroquel XR". Medscape Reference. WebMD. Retrieved 11 October 2013.
- "Quetiapine 25 mg film-coated tablets - Summary of Product Characteristics". electronic Medicines Compendium. Sandoz. January 2013. Retrieved 20 October 2013.
- Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman’s The Pharmacological Basis of Therapeutics (12th ed.). McGraw Hill Professional. ISBN 978-0071624428.
- Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 18]. Greenwood Village, CO: Thomsen Healthcare; 2013.
- "QUETIAPINE FUMARATE tablet QUETIAPINE FUMARATE (quetiapine fumarate ) tablet [Ascend Laboratories, LLC]". DailyMed. Ascend Laboratories, LLC. October 2013. Retrieved 26 November 2013.
- "SEROQUEL". Drug Patent Watch. thinkBiotech LLC. Retrieved 9 July 2012.
- "Novel dibenzothiazepine antipsychotic". US Patent & Trademark Office, Patent Full Text and Image Database. US Patent and Trademark Office. 7 November 1989. Retrieved 9 July 2012.
- "Blockbuster Drugs That Will Go Generic Soon - The Best Life (usnews.com)". Money.usnews.com. 2011-04-29. Retrieved 2012-07-09.
- "Quepin Full Prescribing Information in Drug Reference Encyclopedia". Retrieved 2010-04-03.
- "quetiapine-fumarate". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
- Srisurapanont M, Maneeton B, Maneeton N (2004). "Quetiapine for schizophrenia". In Srisurapanont, Manit. Cochrane database of systematic reviews (Online) (2): CD000967. doi:10.1002/14651858.CD000967.pub2. PMID 15106155.
- Kane JM, Correll CU. Pharmacologic treatment of schizophrenia. Dialogues Clin Neurosci. 2010;12(3):345–57. PMID 20954430.
- Schultz SH, North SW, Shields CG. Schizophrenia: a review. Am Fam Physician. 2007;75(12):1821–9. PMID 17619525.
- Thase ME, Macfadden W, Weisler RH, Chang W, Paulsson B, Khan A, Calabrese JR (2006). "Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression". Journal of Clinical Psychopharmacology 26 (6): 600. doi:10.1097/01.jcp.0000248603.76231.b7. PMID 17110817.
- British National Formulary (BNF) 65. Pharmaceutical Pr; 2013. ISBN 978-0857110848
- Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S (Dec 8, 2010). "Second-generation antipsychotics for major depressive disorder and dysthymia.". The Cochrane database of systematic reviews (12): CD008121. doi:10.1002/14651858.CD008121.pub2. PMID 21154393.
- Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC. Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes. PLoS Med [Internet]. 2013 Mar 12 [cited 2013 Oct 9];10(3) e1001403. Available from: http://dx.doi.org/10.1371/journal.pmed.1001403
- British National Formulary (BNF) 65. London, UK: Pharmaceutical Press. 2013. p. 235. ISBN 9780857110848.
- Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- 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 (2005). "Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial". BMJ 330 (7496): 874. doi:10.1136/bmj.38369.459988.8F. PMC 556156. PMID 15722369.
- Coe HV, Hong IS (May 2012). "Safety of low doses of quetiapine when used for insomnia". The Annals of pharmacotherapy 46 (5): 718–22. doi:10.1345/aph.1Q697. PMID 22510671.
- Off-Label Use of Atypical Antipsychotics: An Update. September 2011. PMID 22132426.
- Mukaddes NM, Abali O (2003). "Quetiapine Treatment of Children and Adolescents with Tourette's Disorder". Journal of Child and Adolescent Psychopharmacology 13 (3): 295. doi:10.1089/104454603322572624. PMID 14642017.
- Oliver Sacks "Musicophilia" Knopf NY 2007 P.67
- Becker PM (2006). "Treatment of sleep dysfunction and psychiatric disorders". Current Treatment Options in Neurology 8 (5): 367–375. doi:10.1007/s11940-006-0026-6. PMID 16901376.
- Shotbolt P, Samuel M, David A (November 2010). "Quetiapine in the treatment of psychosis in Parkinson’s disease". Therapeutic Advances in Neurological Disorders 3 (6): 339–350. doi:10.1177/1756285610389656. PMC 3002640. PMID 21179595.
- Taylor, D; Carol, P; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 9780470979693.
- "PRODUCT INFORMATION STADA(TM) Quetiapine (quetiapine fumarate Tablets 25 mg, 100 mg, 200 mg, 300 mg)". TGA eBusiness Services. STADA Pharmaceuticals Australia Pty Limited. 30 November 2012. Retrieved 19 September 2013.
- 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 (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". The Lancet 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019.
- Erkan, A; Pirildar, S; Acarer, A; Akdeniz, F (2011). "Efficacy of Low-dose Pramipexole Augmentation in the Treatment of Refractory Psychotic Depression Complicated with Tardive Dyskinesia A Case Report" (PDF). Bulletin of Clinical Psychopharmacology (in Turkish) 21 (4): 353–355. doi:10.5455/bcp.20111029071711.
- AlterNet / By Martha Rosenberg (2010-03-06). "Are Veterans Being Given Deadly Cocktails to Treat PTSD? | World". AlterNet. Retrieved 2012-07-09.
- "Questions loom over drug for sleepless vets - Marine Corps News | News from Afghanistan & Iraq". Marine Corps Times. Retrieved 2012-07-09.
- "Unsafe Drugs - Seroquel - Information on AstraZeneca's Psychotropic Medication Seroquel. Seroquel Serious Side Effects Including for People with Diabetes, History of High Blood Sugar and Obesity". Seroquel.legalview.com. Retrieved 2012-07-09.
- By DUFF WILSON Published: July 18, 2011 (2011-07-19). "Heart Warning Added to Label on Popular Antipsychotic Drug". NyTimes. Retrieved 2012-07-09.
- "Seroquel linked to deadly side-effects". Defending The Consumer. Retrieved 2012-07-09.
- "Attorney Bob Goldwater, Robert Goldwater, Seroquel Side Effects". Bobgoldwaterattorney-seroquel.com. Retrieved 2012-07-09.
- "Seroquel & Diabetes Pancreatitis side effects, Lawsuit". Resource4thepeople.com. Retrieved 2012-07-09.
- Shankar Vedantam (2009-03-18). "A Silenced Drug Study Creates An Uproar". The Washington Post.
- Correll CU, Schenk EM (March 2008). "Tardive dyskinesia and new antipsychotics". Current opinion in psychiatry 21 (2): 151–6. doi:10.1097/YCO.0b013e3282f53132. PMID 18332662.
- Aia PG, Revuelta GJ, Cloud LJ, Factor SA; Revuelta, GJ; Cloud, LJ; Factor, SA (2011). "Tardive Dyskinesia". Current treatment options in neurology 13 (3): 231–241. doi:10.1007/s11940-011-0117-x. PMID 21365202.
- Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis Am J Psychiatry 1999;156:1686-1696.
- Seroquel website
- Seroquel Prescribing Information
- Tiihonen, J.; Lönnqvist, J.; Wahlbeck, K.; Klaukka, T.; Niskanen, L.; Tanskanen, A.; Haukka, J. (2009). "11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study)" (PDF). The Lancet 374 (9690): 620–627. doi:10.1016/S0140-6736(09)60742-X.
- Group, BMJ, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. "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."
- Kim DR, Staab JP (May 2005). "Quetiapine discontinuation syndrome". Am J Psychiatry 162 (5): 1020. doi:10.1176/appi.ajp.162.5.1020. PMID 15863814.
- Michaelides C, Thakore-James M, Durso R (Jun 2005). "Reversible withdrawal dyskinesia associated with quetiapine". Mov Disord 20 (6): 769–70. doi:10.1002/mds.20427. PMID 15747370.
- Chouinard, G.; Jones, BD. (Jan 1980). "Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics". Am J Psychiatry 137 (1): 16–21. PMID 6101522.
- Miller, R.; Chouinard, G. (Nov 1993). "Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia". Biol Psychiatry 34 (10): 713–38. doi:10.1016/0006-3223(93)90044-E. PMID 7904833.
- Chouinard G, Jones BD, Annable L (Nov 1978). "Neuroleptic-induced supersensitivity psychosis". Am J Psychiatry 135 (11): 1409–10. PMID 30291.
- Seeman P, Weinshenker D, Quirion R, Srivastava LK, Bhardwaj SK, Grandy DK, Premont RT, Sotnikova TD, Boksa P, El-Ghundi M, O'dowd BF, George SR, Perreault ML, Männistö PT, Robinson S, Palmiter RD, Tallerico T (Mar 2005). "Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis". Proc Natl Acad Sci U S A 102 (9): 3513–8. doi:10.1073/pnas.0409766102. PMC 548961. PMID 15716360.
- Moncrieff J (Jul 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatr Scand 114 (1): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655.
- R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1355–1357.
- AstraZeneca Pharmaceuticals LP (March 2011). "SEROQUEL (quetiapine fumarate) tablet, extended release". DailyMed. National Library of Medicine. Section 12.2: Pharmacodynamics. Retrieved 2011-04-26.
- National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Sep 18]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
- Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. N-Desalkylquetiapine, a Potent Norepinephrine Reuptake Inhibitor and Partial 5-HT1A Agonist, as a Putative Mediator of Quetiapine’s Antidepressant Activity. Neuropsychopharmacology [Internet]. 2007 Dec 5 [cited 2013 Sep 18];33(10):2303–12. Available from: http://www.nature.com/npp/journal/v33/n10/full/1301646a.html
- López-Muñoz F, Álamo C. Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders. Front Psychiatry [Internet]. 2013 [cited 2013 Sep 19];4:102. Available from: http://www.frontiersin.org/Neuropharmacology/10.3389/fpsyt.2013.00102/abstract
- AstraZeneca. Seroquel (quietapine fumarate) tablets (PDF). 276521.
- Richelson E, Souder T (November 2000). "Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds". Life Sciences 68 (1): 29–39. doi:10.1016/S0024-3205(00)00911-5. PMID 11132243.
- Davis, Kenneth L; Neuropsychopharmacology, American College of (2002). Neuropsychopharmacology: the fifth ... - Google Books. ISBN 978-0-7817-2837-9.
- "Seroquel Official FDA information, side effects and uses". Drugs.com. Retrieved 2012-07-09.
- Guzman, F. "Mechanism of action of quetiapine". Psychopharmacology Institute. Retrieved 20 January 2013.
- Kapur S, Seeman P; Seeman, P (2001). "Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?:a new hypothesis". American Journal of Psychiatry 158 (3): 360–369. doi:10.1176/appi.ajp.158.3.360. PMID 11229973.
- Seeman P (2002). "Atypical antipsychotics: mechanism of action". Can J Psychiatry 47 (1): 27–38. PMID 11873706.
- Warawa, E. J.; Migler, B. M.; 1988, U.S. Patent 4,879,288.
- Richelson E, Souder T (November 2000). "Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds". Life Sciences 68 (1): 29–39. doi:10.1016/S0024-3205(00)00911-5. PMID 11132243.
- Gefvert O, Lundberg T, Wieselgren IM, Bergström M, Långström B, Wiesel F, Lindström L (April 2001). "D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study". European Neuropsychopharmacology 11 (2): 105–110. doi:10.1016/S0924-977X(00)00133-4. PMID 11313155.
- Oregon State University Drug Use Evaluation: Low-Dose Quetiapine (Seroquel, Seroquel XR) PDF
- "AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR. For the treatment of schizophrenia." (Press release). AstraZeneca. 2006-07-18. Retrieved 2007-01-01.
- "AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation SEROQUEL XR for the Treatment of Schizophrenia" (Press release). AstraZeneca. 2006-10-19. Retrieved 2007-01-01.
- "FDA Approves AstraZeneca’s Once-Daily SEROQUEL XR Extended-Release Tablets For The Treatment Of Schizophrenia" (Press release). AstraZeneca. 2007-05-18. Retrieved 2007-08-02.
- "Second Quarter and Half Year Results 2007" (Press release). AstraZeneca. 2007-07-26. Retrieved 2007-08-02.
- "Seroquel XR Receives Approval from FDA for Maintenance Treatment of Schizophrenia" (Press release). AstraZeneca. 2007-11-16. Retrieved 2007-12-03.
- Notice of Compliance Information - Seroquel XR September 27, 2007, retrieved December 3, 2007
- "Biovail Announces Filing of ANDA for Quetiapine XR Tablets" (Press release). Biovail. 2008-12-28.
- "AstraZeneca Receives FDA Complete Response Letter on Seroquel XR for Major Depressive Disorder" (Press release). AstraZeneca. 2008-12-24. Retrieved 2008-12-28.
- "Pharmaceutical Giant AstraZeneca to Pay $520 Million for Off-label Drug Marketing". Justice news, US Department of Justice. Retrieved 2012-07-16.
- Guzman, F. "Quetiapine Indications: FDA-Approved and Off-label Uses". Psychopharmacology Institute. Retrieved 19 January 2013.
- "QUETIAPINE FUMARATE". Electronic Orange Book. Food and Drug Administration. April 2007. Retrieved 2007-05-24.
- "AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania" (Press release). AstraZeneca. 2004-01-13.
- "April 7–8, 2009: Psychopharmacologic Drugs Advisory Committee Meeting Announcement". Retrieved 2009-08-27.
- Ann Knef (2007-08-02). "Seroquel suit claims 'so much' is poured into marketing and away from research". The Madison / St. Clair Record.
- Phil Milford (2009-03-11). "AstraZeneca May Link Seroquel, Diabetes, Doctor Says". Bloomberg.com (Bloomberg L.P.).
- March 19, 2010 (2010-03-19). "AstraZeneca wins bellwether Seroquel case". FiercePharma. Retrieved 2012-07-09.
- "AstraZeneca pays out million dollar damages". The Local. 2010-08-09.
- Maura Lerner and Janet Moore (March 19, 2009). "Once-secret drug-company records put U on the spot". Minneapolis Star Tribune. Retrieved 2 December 2012.
- Wilson, Duff (2009-10-29). "AstraZeneca Pays Millions to Settle Seroquel Cases". New York Times. Retrieved 2010-03-09.
- Elliott, Carl (September–October 2010). "The Deadly Corruption of Clinical Trials". Mother Jones. Retrieved 2 December 2012.
- Couzin-Frankel, Jennifer (December 7, 2010). "Minnesota bioethicists critique their university". Science. Retrieved 2 December 2012.
- Matthew Perrone (August 30, 2010). "Questions loom over drug given to sleepless vets". Associated Press. Retrieved April 25, 2013.
- Sydney Morning Herald
- Joseph M. Pierre, M.D., Igor Shnayder, M.D., Donna A. Wirshing, M.D., and William C. Wirshing, M.D. "Intranasal Quetiapine Abuse". American Psychiatric Association.
- Waters BM, Joshi KG (January 2007). "Intravenous Quetiapine-Cocaine Use ("Q-Ball")". Am J Psychiatry (American Psychiatric Association) 164 (1): 173–a–174. doi:10.1176/appi.ajp.164.1.173-a. PMID 17202567.
- Pierre JM, Shnayder I, Wirshing DA, Wirshing WC (September 2004). "Intranasal Quetiapine Abuse". Am J Psychiatry (American Psychiatric Association) 161 (9): 1718. doi:10.1176/appi.ajp.161.9.1718. PMID 15337673.
- Pinta ER, Taylor RE (2007). "Quetiapine Addiction?". American Journal of Psychiatry 164 (1): 174. doi:10.1176/appi.ajp.164.1.174. PMID 17202569.
- "Press releases". MHRA. Retrieved 2012-07-09.
- "Drug Alerts". MHRA. Retrieved 2012-07-09.
- "BBC News - Nurofen Plus tampering: Christopher McGuire jailed". Bbc.co.uk. 2012-05-28. Retrieved 2012-07-09.
- "Quetiapine". MedlinePlus. The American Society of Health-System Pharmacists, Inc. 2008-09-01.
- NAMI summary
- Internet Drug List summary
- Compound #1802: Quetiapine ChemBank
- Intranasal Quetiapine Abuse
- U.S. National Library of Medicine: Drug Information Portal - Quetiapine
- Seroquel Adverse Events Reported to the FDA
- Australian Public Assessment Report for Quetiapine (as fumarate)