Quetiapine

Quetiapine
Systematic (IUPAC) name
2-(2-(4-dibenzo[b,f][1,4]thiazepine- 11-yl- 1-piperazinyl)ethoxy)ethanol
Identifiers
CAS number 111974-69-7
ATC code N05AH04
PubChem CID 5002
IUPHAR ligand 50
DrugBank DB01224
ChemSpider 4827
Chemical data
Formula C21H25N3O2S 
Mol. mass 383.5099 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 9%
Metabolism Hepatic
Half-life 6 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat. C(US)
Legal status ℞-only (US)
Routes Oral
 YesY(what is this?)  (verify)

Quetiapine (pronounced /kwɨˈtaɪ.əpiːn/ kwi-TYE-ə-peen), marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, both as a quetiapine fumarate salt of the drug, is an atypical antipsychotic used in the treatment of schizophrenia, bipolar I mania, bipolar II depression, bipolar I depression, and used off-label for a variety of other purposes, including insomnia and anxiety disorders.

Annual sales are approximately $4.7 billion worldwide, and $2.9 billion in the U.S.[1] The patent in the U.S., which was set to expire in 2011, received a pediatric exclusivity extension, which pushed its expiration to March 26, 2012.[2] The patent already expired in Canada. Several pharmaceutical companies are now making generic versions of quetiapine. Quepin is a generic version manufactured and marketed by Specifar ABEE, Athens, Greece.[3]

Controversy arose over AstraZeneca's aggressive marketing of the Seroquel for off-label uses, including treatment of PTSD in veterans. Several American soldiers and veterans have died while taking Seroquel.[4]

Contents

Uses

Quetiapine (Seroquel) 25 mg tablets, next to US one-cent coin for comparison.

Quetiapine is indicated for the treatment of schizophrenia, depressive episodes associated with bipolar disorder, acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium or valproate), and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex). Quetiapine received its initial indication from the U.S. Food and Drug Administration for treatment of schizophrenia in 1997.[5] In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.[6] It is sometimes used off-label, often as an augmentation agent, to treat conditions such as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression,[7] Tourette syndrome,[8] and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.[9]

In 2005, the National Institute of Mental Health examined quetiapine and other antipsychotics to uncover the comparative efficacy of "second generation" anti-psychotics against older anti-psychotics (known as "first generation" or "typical anti-psychotics"). Such information could be important to the patients, as the newer drugs are far more expensive than their older counterparts. Published in the New England Journal of Medicine, the results of the CATIE ("clinical antipsychotic trials of interventional effectiveness") trial were somewhat mixed. 74% of trial participants (of the 1,493 people who were in different treatment groups) discontinued before the trial ended. The majority of the participants discontinued treatment due to intolerable side effects or lack of efficacy. Olanzapine (Zyprexa) was considered the most effective in terms of the time it took patients to drop out of the study, although it was associated with greater weight gain and glucose intolerability found in diabetes patients. The effects of all other treatments (such as Seroquel) were considered to be similar to the effects of the generic (and dramatically less expensive) drug, perphenazine.[10] The CATIE trial was supported by a grant (N01 MH90001) from the NIMH and by the Foundation of Hope of Raleigh, N.C. The individual pharmaceutical companies, whose drugs were used, donated all of the study medication.

A report in British Medical Journal in 2005 showed that quetiapine was ineffective in reducing agitation among Alzheimer's patients, whose usage of the drug constituted 29% of sales. In fact, quetiapine was found to worsen cognitive functioning in elderly patients with dementia.[11]

Use of quetiapine to minimize the symptoms of opioid withdrawal has been studied.[12]

Investigations

In 2007 and 2008, studies were conducted on quetiapine’s efficacy in treating generalized anxiety disorder and major depression. In April 2009, the Psychopharmacologic Drugs Advisory Committee of the US Food and Drug Administration (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.[13]

Pharmacology

Quetiapine has the following pharmacological actions:[14][15][16]

This means Quetiapine is dopamine, serotonin and adrenergic antagonist, anticholinergic substance and antihistamine. Quetiapine binds strongly to serotonin receptors. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor.[17] 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.

Forms

Quetiapine is available under the brand name Seroquel and Ketipinor. 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.

Dosage

At very low doses (<25 mg), quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α1-adrenergic blocker. After 50 mg quetiapine binds more and more serotonin receptors and at high doses (over 200 mg) quetiapine starts blocking significant amounts of dopamine receptors. [18]

To treat bipolar or schizophrenia, AstraZeneca recommends using 200–800 mg a day range, split into two or three doses a day. For chronic insomnia, 100 mg a night is typically used. However, the use of quetiapine for insomnia is not recommended, as it is antipsychotic medication designed to treat psychotic symptoms, and there is a danger of neurological and cognitive side effects.[19]

Due to compensatory changes at dopamine, serotonin, 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, nausea, emesis, lightheadedness, diaphoresis, orthostasis, tachycardia, and nervousness , dizziness, headache, and anxiety. The present evidence suggests that these symptoms affect a small number of susceptible individuals treated with quetiapine.[20] Rebound insomnia symptoms can occur during withdrawal of quetiapine.

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.[21]

Sustained-release quetiapine

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.[22][23] AstraZeneca will retain the exclusive right to market sustained release quetiapine until 2017. The sustained-release quetiapine is marketed mainly as Seroquel XR. Other marketing names are Seroquel Prolong and Seroquel Depot.

On May 18, 2007, AstraZeneca announced that the FDA approved Seroquel XR for acute treatment of schizophrenia.[24] During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.[25] 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.[26] 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.[27]

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 has accepted the company's ANDA to market its own version of sustained-release quetiapine.[28] Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR.

On December 24, 2008, AstraZeneca notified shareholders that the FDA has asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression.[29]

Side effects

The most common side effect of quetiapine is sedation,[30] and it is marketed as one of the most sedating of all antipsychotics, albeit those claims are contested.[31] 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. Although the FDA approves quetiapine only for the treatment of schizophrenia and bipolar disorder, it is frequently prescribed off-label for other 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.

Six to seven percent of patients may experience tachycardia. Less common side effects (less than 1% of patients) include abnormal liver tests, dizziness, upset stomach, substantial weight gain, a stuffy nose, akathisia, increased paranoia and diabetes.

There is a risk of development of tardive dyskinesia, an incurable neurological disorder, with any prolonged or high dose (over 200 mg) use of quetiapine and some other neuroleptic drugs.[32][33]

The rare, but life-threatening, neuroleptic malignant syndrome may also result from quetiapine use.

Weight gain can be a problem for some patients, as quetiapine causes the patient's appetite to persist even after meals. However, this effect may occur to a lesser degree compared to some other atypical 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.[34] A Delaware state court is scheduled to hear a trial alleging a link between Seroquel and diabetes in June 2009.[35] The Delaware case will be the first case to go to trial on allegations that AstraZeneca withheld information about a link between Seroquel and diabetes.[35] However, the jury decided that the warnings on its label were adequate, so patients and doctors should have had enough information about the drug's risks with respect to diabetes.[36]

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[37] 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 caution in combination with drugs such as bupropion.

A recent comparative study of antipsychotics drugs has found that quetiapine mono treatment was associated with increased risk of death relative to the other analyzed treatments.[38]

As quetiapine is anticholinergic substance it can cause memory and learning deficits.

Following AstraZeneca being sued by 22,000 Americans in connection with side effects from Seroquel, including among other things a heightened risk for diabetes, the company has agreed to pay $198 million in damages to around 17,500 people in the USA.[39]

Withdrawal effects

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.[21] Due to compensatory changes at dopamine, serotonin, and histamine receptor sites in the central nervous system, withdrawal symptoms can occur during abrupt or over-rapid reduction in dosage. Withdrawal symptoms reported to occur after discontinuation of quetiapine include, nausea, emesis, lightheadedness, diaphoresis, dyskinesia, orthostasis, tachycardia, nervousness, dizziness, headache, and anxiety. The present evidence suggests that these symptoms affect a small number of susceptible individuals treated with quetiapine.[20][40] Rebound insomnia symptoms can also occur during withdrawal of quetiapine.

Overdosage

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.[41]

Recreational use

Quetiapine is not 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.[42] This is commonly referred to as a "Q-Ball".[42] 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. Because not all inmates are seen for services, the estimated percent of the total inmate population who appeared to be faking symptoms to obtain quetiapine would be less than 30%.[43] 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 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”.[44]

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. Quetiapine may be used as a substitute to addictive benzodiazepines or sleeping tablets such as zolpidem because it often induces similar sedative effects on the patient.

Federal investigations

In October, 2009 AstraZeneca said that it had reached a $520 million agreement to settle two (US) federal investigations and two whistle-blower lawsuits over the sale and marketing of its psychiatric drug Seroquel.[45]

One of the investigations related to “selected physicians who participated in clinical trials involving Seroquel,” AstraZeneca disclosed in a government filing. The other case related to off-label promotion of the drug.

As a result of aggressive marketing, Seroquel has been increasingly used for children and elderly people for indications not approved by the Food and Drug Administration. Doctors are permitted to prescribe any approved drug for off-label uses.

Seroquel was the top-selling antipsychotic drug in America. It had $17 billion in sales in the United States since 2004, according to IMSHealth, a research firm.

Tony Jewell, a company spokesman, declined to be more specific about the physicians or clinical trials under investigation. He said the company was in final negotiations to settle the whistle-blower suits and reach a corporate integrity agreement with the Justice Department.

The names of the whistle-blowers and other details of the suits remained sealed in federal court.

Chemistry

Quetiapine syn.png

Warawa, E. J.; Migler, B. M.; 1988, U.S. Patent 4,879,288.

"Astra-Zeneca, maker of Seroquel, has been ordered to pay $520 Million dollars to settle the Justice Department's lawsuit against them for improperly promoting its anti psychotic medication Seroquel. The Justice Department claimed that A-Z marketed the drug as treatment for aggression, Alzheimer's disease, anxiety, depression and post-traumatic stress disorder (PTSD)." April 27, 2010 6:16 pm.

Source:http://health.gather.com/viewArticle.action?articleId=281474978201324

References

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  2. ↑ Seroquel patent expiration
  3. ↑ "Quepin Full Prescribing Information in Drug Reference Encyclopedia". http://www.theodora.com/drugs/quepin_tablets_specifar.html. Retrieved 2010-04-03. .
  4. ↑ Matthew Perrone (August 30, 2010). "Questions loom over drug given to sleepless vets". Associate Press. http://www.google.com/hostednews/ap/article/ALeqM5iPPHBQ6w28w4kTXzANGm6kCzPN1gD9HTJO700. Retrieved August 30, 2010. 
  5. ↑ "QUETIAPINE FUMARATE". Electronic Orange Book. Food and Drug Administration. April 2007. http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020639&TABLE1=OB_Rx. Retrieved 2007-05-24. 
  6. ↑ AstraZeneca (2004-01-13). "AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania". Press release. http://www.prnewswire.co.uk/cgi/news/release?id=115109. 
  7. ↑ Croissant B, Klein O, Gehrlein L, Kniest A, Hermann D, Diehl A, Mann K. (December 2006). "Quetiapine in relapse prevention in alcoholics suffering from craving and affective symptoms: a case series". Eur Psychiatry 21 (8): 570–573. doi:10.1016/j.eurpsy.2006.04.007. PMID 17161284. 
  8. ↑ Quetiapine treatment of children and adolescents with Tourette's disorder. Fall 2003, retrieved January 27, 2007.
  9. ↑ Becker PM (September 2006). "Treatment of sleep dysfunction and psychiatric disorders". Curr Treat Options Neurol 8 (5): 367–375. doi:10.1007/s11940-006-0026-6. PMID 16901376. 
  10. ↑ Jeffrey A. Lieberman, T. Scott Stroup, Joseph P. McEvoy, Marvin S. Swartz, Robert A. Rosenheck, Diana O. Perkins, Richard S.E. Keefe, Sonia M. Davis, Clarence E. Davis, Barry D. Lebowitz, Joanne Severe, and John K. Hsiao (2005-09-22). "Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia". New England Journal of Medicine 353 (12): 1209–1223. doi:10.1056/NEJMoa051688. PMID 16172203. http://content.nejm.org/cgi/content/full/353/12/1209. 
  11. ↑ 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 (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. PMID 15722369. PMC 556156. http://www.bmj.com/cgi/content/full/330/7496/874. 
  12. ↑ Pinkofsky HB, Hahn AM, Campbell FA, Rueda J, Daley DC, Douaihy AB (2005). "Reduction of opioid-withdrawal symptoms with quetiapine". J Clin Psychiatry 66 (10): 1285–1288. doi:10.4088/JCP.v66n1011. PMID 16259542. 
  13. ↑ "April 7–8, 2009: Psychopharmacologic Drugs Advisory Committee Meeting Announcement". http://www.fda.gov/AdvisoryCommittees/Calendar/ucm136250.htm. Retrieved 2009-08-27. 
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  15. ↑ 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. http://linkinghub.elsevier.com/retrieve/pii/S0024320500009115. 
  16. ↑ Davis, Kenneth L; Neuropsychopharmacology, American College of (2002). Neuropsychopharmacology: the fifth ... - Google Books. ISBN 9780781728379. http://books.google.com/?id=BKwkonZwZD0C&pg=PA778#v=onepage&q=. 
  17. ↑ Kapur, S.; 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. http://ajp.psychiatryonline.org/cgi/content/abstract/158/3/360. 
  18. ↑ E. Richelson and T. Souder (November 2000). "Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds". Life Sciences 68 (1): 29-39. PMID 11132243. 
  19. ↑ Breggin, P. R. (1990) Brain damage, dementia and persistent cognitive dysfunction associated with neuroleptic drugs. Evidence, etiology, implications. Journal of Mind and Behavior, 11, 425 64 Brain damage, dementia and persistent cognitive dysfunction associated with neuroleptic drugs. Evidence, etiology, implicationsPDF (11.3 MiB)
  20. ↑ 20.0 20.1 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. http://ajp.psychiatryonline.org/cgi/content/full/162/5/1020. 
  21. ↑ 21.0 21.1 Group, BMJ, ed (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 0260-535X. "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." 
  22. ↑ AstraZeneca (2006-07-18). "AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR. For the treatment of schizophrenia.". Press release. http://www.astrazeneca.com/pressrelease/5256.aspx. Retrieved 2007-01-01. 
  23. ↑ AstraZeneca (2006-10-19). "AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation SEROQUEL XR for the Treatment of Schizophrenia". Press release. http://www.astrazeneca.com/pressrelease/5275.aspx. Retrieved 2007-01-01. 
  24. ↑ AstraZeneca (2007-05-18). "FDA Approves AstraZeneca’s Once-Daily SEROQUEL XR Extended-Release Tablets For The Treatment Of Schizophrenia". Press release. http://www.astrazeneca.com/pressrelease/5330.aspx. Retrieved 2007-08-02. 
  25. ↑ AstraZeneca (2007-07-26). "Second Quarter and Half Year Results 2007". Press release. http://www.astrazeneca.com/pressrelease/5341.aspx. Retrieved 2007-08-02. 
  26. ↑ AstraZeneca (2007-11-16). "Seroquel XR Receives Approval from FDA for Maintenance Treatment of Schizophrenia". Press release. http://www.astrazeneca.com/pressrelease/5360.aspx. Retrieved 2007-12-03. 
  27. ↑ Notice of Compliance Information - Seroquel XR September 27, 2007, retrieved December 3, 2007
  28. ↑ Biovail (2008-12-28). "Biovail Announces Filing of ANDA for Quetiapine XR Tablets". Press release. http://www.biovail.com/english/Investor%20Relations/Latest%20News/default.asp?s=1&state=showrelease&releaseid=1230930. 
  29. ↑ AstraZeneca (2008-12-24). "AstraZeneca Receives FDA Complete Response Letter on Seroquel XR for Major Depressive Disorder". Press release. http://www.astrazeneca.com/media/latest-press-releases/seroquel-MDD-FDA-response?itemId=4477598. Retrieved 2008-12-28. 
  30. ↑ Jon A. Shaw, John E. Lewis, Shlomo Pascal, Rakesh K. Sharma, Rosemarie A. Rodriguez, Ramiro Guillen, Marilyn Pupo-Guillen (2001-12-01). "A Study of Quetiapine: Efficacy and Tolerability in Psychotic Adolescents". Journal of Child and Adolescent Psychopharmacology 11 (4): 415–424. doi:10.1089/104454601317261591. PMID 11838824. http://www.liebertonline.com/doi/abs/10.1089/104454601317261591. 
  31. ↑ Shankar Vedantam (2009-03-18). "A Silenced Drug Study Creates An Uproar". The Washington Post. http://www.washingtonpost.com/wp-dyn/content/article/2009/03/17/AR2009031703786.html. 
  32. ↑ S. Nassir Ghaemi and James Y. Ko (October 2001). "Quetiapine-related tardive dyskinesia". Am J Psychiatry 158 (10): 1737. doi:10.1176/appi.ajp.158.10.1737. PMID 11579018. 
  33. ↑ D. Ghelber and R.H. Belmaker (May 1999). "Tardive dyskinesia with quetiapine". Am J Psychiatry 156 (5): 796–797. PMID 10327920. 
  34. ↑ Ann Knef (2007-08-02). "Seroquel suit claims 'so much' is poured into marketing and away from research". The Madison St. Clair Record. http://www.madisonrecord.com/news/198781-seroquel-suit-claims-so-much-is-poured-into-marketing-and-away-from-research. 
  35. ↑ 35.0 35.1 Phil Milford (2009-03-11). "AstraZeneca May Link Seroquel, Diabetes, Doctor Says". Bloomberg.com (Bloomberg L.P.). http://www.bloomberg.com/apps/news?pid=newsarchive&sid=ayzJsK2HlF6s. 
  36. ↑ http://www.fiercepharma.com/story/astrazeneca-wins-bellwether-seroquel-case/2010-03-19
  37. ↑ Seroquel website
  38. ↑ doi:10.1016/S0140-6736(09)60742-X
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  39. ↑ "AstraZeneca pays out million dollar damages". The Local. 2010-08-09. http://www.thelocal.se/28260/20100809/. 
  40. ↑ 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. 
  41. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1355–1357.
  42. ↑ 42.0 42.1 Brian M. Waters and Kaustubh G. Joshi (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. http://ajp.psychiatryonline.org/cgi/content/full/164/1/173-a. 
  43. ↑ Joseph M. Pierre, Igor Shnayder, Donna A. Wirshing, and William Wirshing (September 2004). "Intranasal Quetiapine Abuse". Am J Psychiatry (American Psychiatric Association) 161 (9): 1718. doi:10.1176/appi.ajp.161.9.1718. PMID 15337673. http://ajp.psychiatryonline.org/cgi/content/full/161/9/1718. 
  44. ↑ Emil R. Pinta, and Robert E. Taylor (January 2007). "Quetiapine addiction?". Am J Psychiatry 164 (1): 174. doi:10.1176/appi.ajp.164.1.174. PMID 17202569. http://ajp.psychiatryonline.org/cgi/content/full/164/1/174. 
  45. ↑ Wilson, Duff (2009-10-29). "AstraZeneca Pays Millions to Settle Seroquel Cases". New York Times. http://www.nytimes.com/2009/10/30/business/30drug.html. Retrieved 2010-03-09. 

Further reading

External links

Antipsychotics (neuroleptics) (N05A)
Typical

Benzamides: Levosulpiride • Nemonapride • Sulpiride • Sultopride • Tiapride • Veralipride;
Butyrophenones: Azaperone • Benperidol • Bromperidol • Droperidol • Fluanisone • Haloperidol • Lenperone • Moperone • Pipamperone • Spiperone • Timiperone • Trifluperidol;
Diphenylbutylpiperidines: Clopimozide • Fluspirilene • Penfluridol • Pimozide;
Phenothiazines: Acepromazine • Acetophenazine • Butaperazine • Carphenazine • Chloracizine • Chlorproethazine • Chlorpromazine • Cyamemazine • Dixyrazine • Fluacizine • Fluphenazine • Levomepromazine/Methotrimeprazine • Mesoridazine • Perazine • Periciazine • Perphenazine • Piperacetazine • Pipotiazine • Prochlorperazine • Promazine • Promethazine • Propiomazine • Sulforidazine • Thiethylperazine • Thiopropazate • Thioproperazine • Thioridazine • Trifluoperazine • Triflupromazine;
Thioxanthenes: Chlorprothixene • Clopenthixol • Flupentixol • Thiothixene • Zuclopenthixol;
Tricyclics: Amoxapine • Butaclamol • Fluotracen • Loxapine • Metitepine/Methiothepin • Octoclothiepin • Trimipramine;


Others: Prothipendyl
Atypical

Benzamides: Amisulpride • Remoxipride;
Butyrophenones: Cinuperone • Setoperone;
Benzo(iso)oxazolepiperidines: Iloperidone • Ocaperidone • Paliperidone • Risperidone;
Benzo(iso)thiazolepiperazines: Lurasidone • Perospirone • Revospirone • Tiospirone • Ziprasidone;
Diphenylbutylpiperazines: Amperozide;
Phenylpiperazines: Aripiprazole • Bifeprunox • Elopiprazole • Umespirone;
Tricyclics: Asenapine • Carpipramine • Clocapramine • Clotiapine • Clozapine • Fluperlapine • Gevotroline • Metitepine/Methiothepin • Mosapramine • NDMC • Olanzapine • Piquindone • Quetiapine • Tenilapine • Zotepine;


Others: Blonanserin • Cariprazine • Molindone • Pimavanserin • Roxindole • Sarizotan • Sertindole • Spiramide
Others
Azacyclonol • Cannabidiol • D-Cycloserine • Lithium • Mifepristone • Oxypertine • Reserpine • Rimcazole • Secretin • Talnetant • Tetrabenazine • Vabicaserin
#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III

mepr

dsrd (o, p, m, p, a, d, s), sysi/, spvo

, drug(N5A/5B/5C/6A/6B/)
Tricyclics
Classes
Acridine • Anthracene • Dibenzazepine • Dibenzocycloheptene • Dibenzodiazepine • Dibenzothiazepine • Dibenzothiepin • Dibenzoxazepine • Dibenzoxepin • Phenothiazine • Pyridazinobenzoxazine • Pyridinobenzodiazepine • Thioxanthene
Antidepressants
7-OH-Amoxapine • Amezepine • Amineptine • Amitriptyline • Amitriptylinoxide • Amoxapine • Aptazapine • Azepindole • Azipramine • Butriptyline • Cianopramine • Ciclazindol • Ciclopramine • Clomipramine • Cotriptyline • Cyanodothiepin • Demexiptiline • Depramine/Balipramine • Desipramine • Dibenzepine • Dimetacrine • Dosulepin/Dothiepin • Doxepin • Enprazepine • Esmirtazapine • Fluotracen • Hepzidine • Homopipramol • Imipramine • Imipraminoxide • Intriptyline • Iprindole • Ketipramine • Litracen • Lofepramine • Losindole • Loxapine • Maprotiline • Mariptiline • Mazindol • Melitracen • Metapramine • Mezepine • Mianserin • Mirtazapine • Naranol • Nitroxazepine • Nortriptyline • Noxiptiline • Octriptyline • Opipramol • Oxaprotiline • Pipofezine • Pirandamine • Propizepine • Protriptyline • Quinupramine • Setiptiline/Teciptiline • Tandamine • Tampramine • Tianeptine • Tienopramine • Trimipramine
Antihistamines
Alimemazine • Azatadine • Clobenzepam • Cyproheptadine • Dacemazine • Deptropine • Desloratadine • Epinastine • Etymemazine • Hydroxyethylpromethazine • Isopromethazine • Isothipendyl • Ketotifen • Latrepirdine • Loratadine • Mebhydrolin • Mequitazine • Methdilazine • Olopatadine • Oxomemazine • Phenindamine • Pimethixene • Promethazine • Propiomazine • Rupatadine • Thiazinamium
Antipsychotics
Acetophenazine • Amoxapine • Asenapine • Butaclamol • Butaperazine • Carphenazine • Carpipramine • Chlorpromazine • Chlorprothixene • Ciclindole • Clocapramine • Clomacran • Clotiapine • Clozapine • Flucindole • Fluotracen • Flupentixol • Fluphenazine • Gevotroline • Homopipramol • Levomepromazine/Methotrimeprazine • Loxapine • Maroxepin • Mesoridazine • Metitepine/Methiothepin • Metoxepin • Mosapramine • Naranol • Olanzapine • Perazine • Perphenazine • Periciazine • Piperacetazine • Pipotiazine • Piquindone • Prochlorperazine • Promazine • Prothipendyl • Quetiapine • Sulforidazine • Thiethylperazine • Thiopropazate • Thioridazine • Thiothixene • Trifluoperazine • Triflupromazine • Zotepine • Zuclopenthixol
Others
Atiprosin • Carbamazepine • Carvedilol • Cyclobenzaprine • Licarbazepine • Methylene Blue • Monatepil • Oxcarbazepine • Oxitriptyline • Pirenzepine • Pirolate • Pitrazepin • Pizotifen • Profenamine