Quetiapine

Drugbox
IUPAC_name = 2-(2-(4-dibenzo ["b,f"] [1,4] thiazepine- 11-yl-1-piperazinyl)ethoxy)ethanol


width = 250



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 = Hepatic
elimination_half-life = 6 hours
excretion = 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 for a variety of other purposes.

Uses

. [cite journal

title = AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania
url = http://www.prnewswire.co.uk/cgi/news/release?id=115109

] 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, [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

] Tourette syndrome, [ [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.] and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders. [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

]

In 2005, quetiapine and other 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, [ [http://www.ahrp.org/cms/content/view/400/94/ New Schizophrenia Drugs No Better Than Cheaper Generics] ] 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. [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

]

Use of quetiapine to minimize the symptoms of opioid withdrawal has been studied. [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=]

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. [ [http://www.astrazeneca.com/article/511390.aspx AstraZeneca—Pipeline Summary—New chemical entities and line extensions] . Retrieved January 5, 2007]

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" and "TV Guide". [http://www.nytimes.com/2007/02/15/us/15bipolar.html "Debate Over Children and Psychiatric Drugs", "New York Times", February 15, 2007.] [ [http://www.dailykos.com/story/2007/7/9/95332/43540 Seroquel is an Antipsychotic.] ] 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, [ [http://www.seroquel.com/cons_bip/seroquel/understand_seroquel/stories.asp Seroquel stories: understanding Seroquel, important safety information] ] observing that teenagers taking quetiapine "may be more likely to think about harming or killing themselves or to plan or try to do so". [ [http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a698019.html National Institutes of Health, Medline guidelines for Quetiapine] ]

Pharmacology

The antipsychotic effect of quetiapine is thought by some to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the D1 and D2 dopamine receptor, the alpha-1 and alpha-2 adrenergic receptor, and 5-HT1A and 5-HT2 serotonin receptor subtypes are antagonized. cite journal

title = Seroquel.pdf
url = http://www1.astrazeneca-us.com/pi/Seroquel.pdf

] Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. [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] 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 H1 receptor. This is thought to be responsible for the sedative effect of the drug. [cite web| title =Schizophrenia: From Circuits to Symptoms | publisher =Medscape Today | url =http://www.medscape.com/viewarticle/484929_8| accessdate =2007-06-05]

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. 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, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia. [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] [ [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] 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. [ [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] During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007. [ [http://www.astrazeneca.com/pressrelease/5341.aspx Second Quarter and Half Year Results 2007] . July 26, 2007, retrieved August 2, 2007] 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. [ [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.] 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. [ [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]

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.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]
] 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, 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 antipsychotics based on the data sources which point to placebo-level incidence of extrapyramidal side effects. [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.] [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.]

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. [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]

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. (Reference needed to April 2006 results of CATIE study.) However, the Seroquel website [ [http://www.seroquel.com/ Seroquel website] ] 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. [ [http://ajp.psychiatryonline.org/cgi/content/full/164/1/173-a Intravenous Quetiapine-Cocaine Use ("Q-Ball")] ] 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". [ [http://ajp.psychiatryonline.org/cgi/content/full/161/9/1718 Intranasal Quetiapine Abuse] ] 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”. [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

]

Along with benzodiazepines, atypical antipsychotics have sometimes been used to "come down" off cocaine or amphetamines. When used in this manner the slang term "downer" is often applied.

References

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]


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