Quetiapine
185384
225932290
2008-07-16T02:10:51Z
Fvasconcellos
1051513
more descriptive lead, minor reorganization
{{Drugbox|
| IUPAC_name = 2-(2-(4-dibenzo[''b,f''][1,4]thiazepine- 11-yl-1-piperazinyl)ethoxy)ethanol
| image = quetiapine2.png
| width = 250
| image2 = Quetiapine-from-xtal-3D-balls.png
| width2 = 150
| CAS_number = 111974-69-7
| ATC_prefix = N05
| ATC_suffix = AH04
| PubChem = 5002
| DrugBank = APRD00675
| C=21|H=25|N=3|O=2|S=1
| molecular_weight = 383.5099 g/mol
| smiles = OCCOCCN1CCN(CC1)C1=Nc2ccccc2Sc2ccccc12
| bioavailability = 9%
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 6 hours
| excretion = [[Kidney|Renal]]
| pregnancy_US = C
| legal_US = Rx-only
| routes_of_administration = Oral
}}
'''Quetiapine''' ({{pron-en|kwəˈtɑɪəpiːn}}, kwe-TYE-a-peen), marketed by [[AstraZeneca]] as '''Seroquel''' and by [[Orion Pharma]] as '''Ketipinor''', is an [[atypical antipsychotic]] used in the management of [[schizophrenia]] and [[bipolar I disorder]], and [[off-label use|off-label]] for a variety of other purposes.
== Uses ==
[[Image:Seroquel-25mg.jpg|thumb|left|Quetiapine (Seroquel) 25 mg tablets, next to US one-cent coin for comparison.]] Quetiapine is indicated for the treatment of schizophrenia as well as for the treatment of acute manic episodes associated with [[bipolar I disorder]], as either monotherapy or adjunct therapy to [[Lithium pharmacology|lithium]] or [[divalproex]]. Quetiapine received its initial indication from the [[FDA]] for treatment of [[schizophrenia]] in 1997. In 2004, it received its second indication for the treatment of mania-associated [[bipolar disorder]].<ref>{{cite journal
| title = AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania
| url = http://www.prnewswire.co.uk/cgi/news/release?id=115109
}}</ref> It is sometimes used [[off-label]], often as an augmentation agent, to treat such conditions as [[obsessive-compulsive disorder]], [[post-traumatic stress disorder]], [[restless legs syndrome]], [[autism]], [[alcoholism]],<ref>{{cite journal
| journal = Eur Psychiatry
| volume = 2006 Dec;21(8):570-3
| title = Quetiapine in relapse prevention in alcoholics suffering from craving and affective symptoms: a case series
| author = Croissant B, Klein O, Gehrlein L, Kniest A, Hermann D, Diehl A, Mann K.
| pmid = 17161284
}}</ref> [[Tourette syndrome]],<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14642017 Quetiapine treatment of children and adolescents with Tourette's disorder]. Fall 2003, retrieved January 27, 2007.</ref> and has been used by physicians as a [[sedative]] for those with [[sleep disorder]]s or [[anxiety disorder]]s.<ref>{{cite journal
| journal = Curr Treat Options Neurol
| volume = 2006 Sep;8(5):367-75
| title = Treatment of sleep dysfunction and psychiatric disorders
| author = Becker PM
| pmid = 16901376
}}</ref>
In 2005, quetiapine and other "atypical antipsychotics" were shown by the ''[[New England Journal of Medicine]]'' to be no more effective than [[perphenazine]] (Trilafon), a [[typical antipsychotic]], for the treatment of schizophrenia. However, the subsequent CATIE trial, funded by AstraZeneca and other major pharmaceutical manufacturers,<ref>[http://www.ahrp.org/cms/content/view/400/94/ New Schizophrenia Drugs No Better Than Cheaper Generics]</ref> contradicted the 2005 study in certain instances.
A 2005 ''[[British Medical Journal]]'' report showed that quetiapine was ineffective in reducing agitation among Alzheimer's patients, whose consumption of the drug then constituted 29% of sales; in fact, quetiapine was found to make cognitive functioning worse in elderly patients with dementia.<ref>{{cite journal
| journal = BMJ
| volume = 2005;330:874
| title = Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial
| author = Clive Ballard, Marisa Margallo-Lana, Edmund Juszczak, Simon Douglas, Alan Swann, Alan Thomas, John O'Brien, Anna Everratt, Stuart Sadler, Clare Maddison, Lesley Lee, Carol Bannister, Ruth Elvish, Robin Jacoby
| url = http://www.bmj.com/cgi/content/full/330/7496/874
| pmid = 15722369
| doi = 10.1136/bmj.38369.459988.8F
| year = 2005
| pages = 874
}}</ref>
Use of quetiapine to minimize the symptoms of [[opioid]] [[withdrawal]] has been studied.<ref>{{cite journal |author=Pinkofsky HB, Hahn AM, Campbell FA, Rueda J, Daley DC, Douaihy AB |title=Reduction of opioid-withdrawal symptoms with quetiapine |journal=J Clin Psychiatry |volume=66 |issue=10 |pages=1285–8 |year=2005 |pmid=16259542 |doi=}}</ref>
[[Clinical trial|Phase III]] trials are being conducted to prove quetiapine's efficacy in treating [[generalized anxiety disorder]] and [[major depressive disorder]] as of January 2007. The company expects to file a New Drug Application for treating generalized anxiety disorder in the second half of 2007 and for major depressive disorder in 2008.<ref>[http://www.astrazeneca.com/article/511390.aspx AstraZeneca—Pipeline Summary—New chemical entities and line extensions]. Retrieved [[January 5]], [[2007]]</ref>
AstraZeneca's patent for Seroquel expires in September 2011, which will allow other companies to manufacture and market quetiapine.
=== In children ===
Quetiapine is controversially marketed to parents of moody and irritable teenagers in magazines such as ''[[Parade (magazine)|PARADE]]'' and ''[[TV Guide]]''.<ref>http://www.nytimes.com/2007/02/15/us/15bipolar.html "Debate Over Children and Psychiatric Drugs", ''New York Times'', February 15, 2007.</ref><ref>[http://www.dailykos.com/story/2007/7/9/95332/43540 Seroquel is an Antipsychotic.]</ref> The [[National Institutes of Health]] recommends against the use of quetiapine and almost all other psychotropic medications (including all atypicals, most antidepressants, and all benzodiazepines) by children or those under 18,<ref>[http://www.seroquel.com/cons_bip/seroquel/understand_seroquel/stories.asp Seroquel stories: understanding Seroquel, important safety information]</ref> observing that teenagers taking quetiapine "may be more likely to think about harming or killing themselves or to plan or try to do so".<ref>[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a698019.html National Institutes of Health, Medline guidelines for Quetiapine]</ref>
== Pharmacology ==
<!-- Deleted image removed: [[Image:Seroquel logo.png|left|frame|Seroquel logo]] -->
The antipsychotic effect of quetiapine is thought by some to be mediated through [[Receptor antagonist|antagonist]] activity at [[dopamine]] and [[serotonin]] receptors. Specifically the [[Dopamine receptor D1|D<sub>1</sub>]] and [[Dopamine receptor D2|D<sub>2</sub>]] [[dopamine receptor]], the [[alpha-1 adrenergic receptor|alpha-1]] and [[alpha-2 adrenergic receptor|alpha-2]] [[adrenergic receptor]], and [[5-HT1A receptor|5-HT<sub>1A</sub>]] and [[5-HT2 receptor|5-HT<sub>2</sub>]] [[serotonin receptor]] subtypes are antagonized.<ref name = Seroquel> {{cite journal
| title = Seroquel.pdf
| url = http://www1.astrazeneca-us.com/pi/Seroquel.pdf
}}</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| title =Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?:a new hypothesis. | publisher =Am J Psychiatry 2001; 158: 360-9 | 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}}</ref> Theoretically, this allows for normal physiological surges of dopamine to elicit their 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]].{{fact|date=November 2007}}
Quetiapine also has an antagonistic effect on the histamine H<sub>1</sub> receptor. This is thought to be responsible for the sedative effect of the drug.<ref>{{cite web| title =Schizophrenia: From Circuits to Symptoms | publisher =Medscape Today | url =http://www.medscape.com/viewarticle/484929_8| accessdate =2007-06-05}}</ref>
== Forms ==
Quetiapine is available under the brand name Seroquel. It was originally available in 25 mg, 50 mg, 100 mg, 200 mg, and 300 mg tablets. 50 mg and 400 mg tablets have since been introduced to increase dosing flexibility.
=== Sustained-release quetiapine (Seroquel XR) ===
AstraZeneca has submitted a [[New Drug Application]] for a [[sustained-release]] version of quetiapine in the [[United States of America|United States]], [[Canada]], and the [[European Union]] in the second half of 2006 for treatment of schizophrenia.<ref>http://www.astrazeneca.com/pressrelease/5256.aspx AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR™. For the treatment of [[schizophrenia]]. [[July 18]], [[2006]], retrieved [[January 1]], [[2007]]</ref><ref>[http://www.astrazeneca.com/pressrelease/5275.aspx AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation SEROQUEL XR™ for the Treatment of Schizophrenia]. [[October 19]], [[2006]], retrieved [[January 1]], [[2007]]</ref> AstraZeneca will retain the exclusive right to market sustained release quetiapine until 2017.
On [[May 18]], [[2007]], AstraZeneca announced that the U.S. [[Food and Drug Administration]] has approved Seroquel XR for acute treatment of schizophrenia.<ref>[http://www.astrazeneca.com/pressrelease/5330.aspx FDA Approves AstraZeneca’s Once-Daily SEROQUEL XR™ Extended-Release Tablets For The Treatment Of Schizophrenia]. [[May 18]], [[2007]], retrieved [[August 2]], [[2007]]</ref> During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.<ref>[http://www.astrazeneca.com/pressrelease/5341.aspx Second Quarter and Half Year Results 2007]. [[July 26]], [[2007]], retrieved [[August 2]], [[2007]]</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>[http://www.astrazeneca.com/pressrelease/5360.aspx Seroquel XR™ Receives Approval from FDA for Maintenance Treatment of Schizophrenia] November 16, 2007. Retrieved December 3, 2007.</ref> The company has not provided a reason for the delay of Seroquel XR's launch.
[[Health Canada]] approved sale of Seroquel XR on [[September 27]], [[2007]].<ref>[http://cpe0013211b4c6d-cm0014e88ee7a4.cpe.net.cable.rogers.com/NocWeb/viewnoce.jsp?noc=kilh Notice of Compliance Information - Seroquel XR] September 27, 2007, retrieved December 3, 2007</ref>
== Side effects ==
Quetiapine has multiple side effects, some of them common, a few of them serious and life-threatening.
The most common [[side effect]] of quetiapine is [[sedation]].<ref name = Shaw>{{cite journal
| author = Jon A. Shaw, John E. Lewis, Shlomo Pascal, Rakesh K. Sharma, Rosemarie A. Rodriguez, Ramiro Guillen, Marilyn Pupo-Guillen
| journal = Journal of Child and Adolescent Psychopharmacology
| volume = December 1, 2001, 11(4): 415-424
| title =[http://www.liebertonline.com/doi/abs/10.1089/104454601317261591 A Study of Quetiapine: Efficacy and Tolerability in Psychotic Adolescents]
| doi =10.1089/104454601317261591 A Study of Quetiapine: Efficacy and Tolerability in Psychotic Adolescents] }}</ref> It is prescribed specifically (off-label) for this effect in patients with sleep disorders. It is one of the most sedating of all antipsychotics, rivaling even the most sedating older drugs. Beginning users may feel extremely tired and 'out of it' for the first few days, 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. Although quetiapine is approved by the FDA for the treatment of [[schizophrenia]] and bipolar disorder, it is frequently prescribed for off-label purposes, including insomnia and the treatment of anxiety disorders. 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.
Common side effects include [[constipation]], [[headache]], [[dry mouth]], weight gain (or loss). Less common side effects (less than 1% of patients) include abnormal liver tests, [[dizziness]], [[nausea|upset stomach]], substantial [[weight gain]] or [[weight loss]], a stuffy nose, [[akathisia]] and increased [[paranoia]].
There is a risk of development of [[tardive dyskinesia]], an incurable [[neurological disorder]], with any prolonged use of quetiapine and some other neuroleptic drugs. However, quetiapine is believed to cause tardive dyskinesia somewhat less often than [[typical antipsychotic|typical]] [[antipsychotic]]s based on the data sources which point to placebo-level incidence of extrapyramidal side effects.<ref>{{cite web|last=Ghaemi|first=S. Nassir, M.D.|coauthors=Ko, James Y., A.B|date=October 2001|url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11579018&dopt=Abstract |title=Quetiapine-related tardive dyskinesia.}}</ref><ref>{{cite web| url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10327920&dopt=Abstract |title=
Tardive dyskinesia with quetiapine.}}</ref>
The rare, but life-threatening, [[neuroleptic malignant syndrome]] may also result from quetiapine use.
Weight gain can be a problem for some patients using quetiapine, by causing the patient's appetite to persist even after meals. However, this effect may occur to a lesser degree compared to some other atypical antipsychotics such as [[olanzapine]] or [[clozapine]]. As with other atypical antipsychotics, there is evidence suggesting a link to the development of [[diabetes]] and [[blood sugar]] disorders, however this remains controversial due to disparities between the results of studies.
In the United States, two separate lawsuits—over claims that quetiapine use has led to diabetes—have been filed in federal court.<ref>{{Cite web | url=http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research%3C/ref | title=Seroquel suit claims 'so much' is poured into marketing and away from research| work = The Madison St. Clair Record}}</ref>
Studies conducted on [[beagle]]s have resulted in the formation of [[cataract]]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>[http://www.seroquel.com/ Seroquel website]</ref> still recommends users have eye examinations every six months.
As with some other antipsychotics, quetiapine may lower the seizure threshold, and should be taken with care in combination with drugs such as [[bupropion]].
== Addiction and abuse ==
Quetiapine is not currently classified as a controlled substance. Reports of quetiapine abuse have emerged in the medical literature, however. While the drug is usually abused through the crushing and snorting of tablets ([[insufflation]]), there have also been reports of intravenous abuse and intravenous co-administration with cocaine.<ref>[http://ajp.psychiatryonline.org/cgi/content/full/164/1/173-a Intravenous Quetiapine-Cocaine Use ("Q-Ball")]</ref> A 2004 report recorded a 30% rate of inmate use in the Los Angeles County Jail, where the drug was obtained by inmates faking schizophrenic symptoms and resold under the street name "quell".<ref>[http://ajp.psychiatryonline.org/cgi/content/full/161/9/1718 Intranasal Quetiapine Abuse]</ref> Also known as "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 which 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”.<ref>{{cite journal
| url = http://ajp.psychiatryonline.org/cgi/content/full/164/1/174
| title = Quetiapine addiction?
| journal = Am J Psychiatry
| volume = 164:174, January 2007
| author = Emil R. Pinta, and Robert E. Taylor
| pmid = 17202569
| doi = 10.1176/appi.ajp.164.1.174
| year = 2007
| pages = 174
}}</ref>
Along with [[benzodiazepines]], atypical antipsychotics have sometimes been used to "come down" off [[amphetamine]]s. When used in this manner the slang term "[[Downers|downer]]" is often applied.
== References ==
<!--See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for an explanation of how to generate footnotes or references using the <ref(erences/)> tags-->
{{reflist|2}}
== External links ==
* [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a698019.html MedlinePlus summary]
* [http://www.nami.org/Template.cfm?Section=About_Medications&template=/ContentManagement/ContentDisplay.cfm&ContentID=8190 NAMI summary]
* [http://www.rxlist.com/cgi/generic/quetiap_ids.htm Internet Drug List summary]
* [http://chembank.broad.harvard.edu/compounds/display.html?compound_id=1802&sets=bioactive&realm=bioactives Compound #1802: Quetiapine] ChemBank
* [http://ajp.psychiatryonline.org/cgi/content/full/161/9/1718 Intranasal Quetiapine Abuse]
*[http://web.archive.org/web/20070202013101/http://www.sprawlmagazine.com/articles/6-4-05happypills.html The Down Side of Happy Pills: Living life medicated]
{{Antipsychotics}}
[[Category:Atypical antipsychotics]]
[[Category:Hypnotics]]
[[Category:Sedatives]]
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