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*'''Schizophrenia:''' 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.<ref>Quetiapine for schizophrenia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000967.pub2/abstract</ref>
*'''Schizophrenia:''' 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.<ref>Quetiapine for schizophrenia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000967.pub2/abstract</ref>
*'''Bipolar disorder:''' In those with bipolar disorder, quetiapine is used to treat depressive episodes and acute manic episodes associated with bipolar I disorder.<ref>Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double-blind, Placebo-controlled Study (The BOLDER II Study) | http://journals.lww.com/psychopharmacology/pages/articleviewer.aspx?year=2006&issue=12000&article=00009&type=abstract</ref><ref>British National Formulary (BNF) 65. Pharmaceutical Pr; 2013. ISBN 978-0857110848</ref>
*'''Bipolar disorder:''' In those with bipolar disorder, quetiapine is used to treat depressive episodes and acute manic episodes associated with bipolar I disorder.<ref>Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double-blind, Placebo-controlled Study (The BOLDER II Study) | http://journals.lww.com/psychopharmacology/pages/articleviewer.aspx?year=2006&issue=12000&article=00009&type=abstract</ref><ref>British National Formulary (BNF) 65. Pharmaceutical Pr; 2013. ISBN 978-0857110848</ref>
*'''Major depressove disorder:''' Quetiapine is effective when used by itself[16] and when used along with other medications in major depressive disorder (MDD).<ref>Second-generation antipsychotics for major depressive disorder and dysthymia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/abstract</ref><ref>Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes | http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001403</ref> However, sedation is often an undesirable side effect.<ref>Second-generation antipsychotics for major depressive disorder and dysthymia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/abstract</ref>
*'''Major depressove disorder:''' Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD).<ref>Second-generation antipsychotics for major depressive disorder and dysthymia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/abstract</ref><ref>Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes | http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001403</ref> However, sedation is often an undesirable side effect.<ref>Second-generation antipsychotics for major depressive disorder and dysthymia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/abstract</ref>
*'''Parkinsons disease:''' 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.<ref>Quetiapine in the treatment of psychosis in Parkinson’s disease | http://tan.sagepub.com/content/3/6/339</ref><ref> Taylor, D; Carol, P; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 9780470979693.</ref>
*'''Parkinsons disease:''' 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.<ref>Quetiapine in the treatment of psychosis in Parkinson’s disease | http://tan.sagepub.com/content/3/6/339</ref><ref> Taylor, D; Carol, P; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 9780470979693.</ref>
*'''Other:''' The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.<ref>Safety of Low Doses of Quetiapine When Used for Insomnia | http://aop.sagepub.com/content/46/5/718</ref><ref>Off-Label Use of Atypical Antipsychotics: An Update [Internet] | http://www.ncbi.nlm.nih.gov/pubmed/22132426</ref> It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,<ref>Journal of Child and Adolescent Psychopharmacology | http://online.liebertpub.com/doi/abs/10.1089/104454603322572624</ref> musical hallucinations<ref>Oliver Sacks "Musicophilia" Knopf NY 2007 P.67</ref> and anxiety disorders.<ref>Treatment of sleep dysfunction and psychiatric disorders | http://link.springer.com/article/10.1007%2Fs11940-006-0026-6</ref>
*'''Other:''' The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.<ref>Safety of Low Doses of Quetiapine When Used for Insomnia | http://aop.sagepub.com/content/46/5/718</ref><ref>Off-Label Use of Atypical Antipsychotics: An Update [Internet] | http://www.ncbi.nlm.nih.gov/pubmed/22132426</ref> It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,<ref>Journal of Child and Adolescent Psychopharmacology | http://online.liebertpub.com/doi/abs/10.1089/104454603322572624</ref> musical hallucinations<ref>Oliver Sacks "Musicophilia" Knopf NY 2007 P.67</ref> and anxiety disorders.<ref>Treatment of sleep dysfunction and psychiatric disorders | http://link.springer.com/article/10.1007%2Fs11940-006-0026-6</ref>

Revision as of 10:32, 16 May 2014

Quetiapine
noframe
noframe
The skeletal formula of Quetiapine.
Dosage (oral)
Threshold 25 mg
Light 25 - 100 mg
Common 75 - 200 mg
Strong 200 - 300 mg
Heavy 300 mg +
Duration (oral)
4 - 8 hours

Quetiapine (/kwɨˈtaɪ.əpiːn/ kwi-ty-ə-peen) (branded as Seroquel, Xeroquel, Ketipinor) is a short-acting atypical antipsychotic approved for the treatment of schizophrenia, bipolar disorder, and along with an antidepressant to treat major depressive disorder.

Recreational usage of this substance is uncommon but reports of quetiapine abuse have emerged within the medical literature. This seems to be driven by its sedative and anxiolytic effects (to help with sleep or to 'calm down') rather than by its antipsychotic properties.[1] In addition to oral administration, the drug is sometimes taken intranasally by insufflating pulverized tablets. Some 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.[2] It is thought that this drug is more commonly abused in prisons than on the street due to its capacity to be regularly prescribed as a sedative and the unavailability in prison of more commonly abused substances.

Annual sales are approximately $5.7 billion worldwide, with $2.9 billion in the United States.[3] The U.S. patent,[4] which was set to expire in 2011, received a pediatric exclusivity extension which pushed its expiration to March 26, 2012.[5][6] 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.[7]

Chemistry

Pharmocology

Quetiapine is a powerful dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with clinically negligible anticholinergic properties.[8][9][10][11] Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors.[12] In terms of its antipsychotic effects, the precise mechanism of action is unknown, but according to the dopamine theory of schizophrenia, antipsychotic effects might be related to the drug’s ability to reduce dopaminergic neurotransmission in the mesolimbic pathway.

Subjective effects

Physical effects

The physical effects of Quetiapine can be broken down into 3 components all of which progressively intensify proportional to dosage. These are described below and generally include:

Cognitive effects

The general head space of Quetiapine is often described as one of sleepiness, emptiness, apathy, stupor and catatonia. The specific cognitive effects can be broken down into 7 components all of which progressively intensify proportional to dosage. These are described below and generally include:

Medical uses

  • Schizophrenia: 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.[13]
  • Bipolar disorder: In those with bipolar disorder, quetiapine is used to treat depressive episodes and acute manic episodes associated with bipolar I disorder.[14][15]
  • Major depressove disorder: Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD).[16][17] However, sedation is often an undesirable side effect.[18]
  • Parkinsons disease: 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.[19][20]
  • Other: The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects.[21][22] It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,[23] musical hallucinations[24] and anxiety disorders.[25]

Toxicity and harm potential

Although simply trying this substance at a low to moderate dosage is considered as quite safe, there is an emerging controversy regarding quetiapine fatalities. Approximately 10,000[26] lawsuits[27][28][29] against AstraZeneca for problems ranging from slurred speech and chronic insomnia to death have been filed by individuals from civilian populations.

Both typical and atypical antipsychotics can cause tardive dyskinesia.[30] According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%.[31] Although Quetiapine and Clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.[32]

Weight gain can be a problem for some, with quetiapine causing more weight gain than other more commonly used Antipsychotics.[33]

Lethal dosage

Compared to other antipsychotics quetiapine has been reported to be relatively safer in overdose.[34] Most instances of acute overdosage result only in sedation, hypotension and tachycardia, but cardiac arrythmia, coma and death have occurred in adults. Quetiapine concentrations within the patients blood 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.[35]

Tolerance and addiction potential

As with other antipsychotics, long term use of quetiapine can be considered addictive and is capable of causing both physical and psychological dependence. When physical dependence has developed, withdrawal symptoms may occur if a person suddenly stops their usage.

The addictive qualities of quetiapine have not been formally studied and are largely known through anecdotal sources. For example, 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”.

Withdrawal symptoms

Withdrawal symptoms reported to occur after discontinuation of quetiapine and other antipsychotics include nausea, emesis, lightheadedness, diaphoresis, dyskinesia, orthostatic hypotension, tachycardia, insomnia, nervousness, dizziness, headache, excessive non-stop crying, and anxiety.[36][37] 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.[38][39]

  • USA: Quetiapine (Seroquel) is unscheduled in the United States, but is available by prescription only. This means that sales and distribution are allowed only by those with a license and only to those with a prescription (according to FDA regulations). Possession is not illegal even without a prescription.
  • UK: Available by prescription only - unscheduled, but unpopular.
  • Austria: Available by prescription only - unscheduled, but unpopular.
  • France: Available by prescription only - unscheduled.

See also

References

  1. ↑ Intranasal quetiapine abuse | http://ajp.psychiatryonline.org/article.aspx?articleid=177055
  2. ↑ Intranasal quetiapine abuse | http://ajp.psychiatryonline.org/article.aspx?articleid=177055
  3. ↑ http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=SEROQUEL
  4. ↑ http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=4,879,288.PN.&OS=PN/4,879,288&RS=PN/4,879,288
  5. ↑ http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=4,879,288.PN.&OS=PN/4,879,288&RS=PN/4,879,288
  6. ↑ Blockbuster Drugs That Will Go Generic Soon | http://money.usnews.com/money/blogs/the-best-life/2011/04/29/blockbuster-drugs-that-will-go-generic-soon
  7. ↑ http://www.theodora.com/drugs/quepin_tablets_specifar.html
  8. ↑ http://www1.astrazeneca-us.com/pi/Seroquel.pdf
  9. ↑ Binding of antipsychotic drugs to human brain receptors: Focus on newer generation compounds | http://www.sciencedirect.com/science/article/pii/S0024320500009115
  10. ↑ Neuropsychopharmocology, a fifth generation of progress | http://books.google.co.uk/books?id=BKwkonZwZD0C&pg=PA778&hl=en#v=onepage&q&f=false
  11. ↑ http://www.drugs.com/pro/seroquel.html
  12. ↑ Mechanism of Action of Quetiapine | http://psychopharmacologyinstitute.com/antipsychotics/quetiapine/mechanism-of-action/
  13. ↑ Quetiapine for schizophrenia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000967.pub2/abstract
  14. ↑ Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double-blind, Placebo-controlled Study (The BOLDER II Study) | http://journals.lww.com/psychopharmacology/pages/articleviewer.aspx?year=2006&issue=12000&article=00009&type=abstract
  15. ↑ British National Formulary (BNF) 65. Pharmaceutical Pr; 2013. ISBN 978-0857110848
  16. ↑ Second-generation antipsychotics for major depressive disorder and dysthymia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/abstract
  17. ↑ Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes | http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001403
  18. ↑ Second-generation antipsychotics for major depressive disorder and dysthymia | http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008121.pub2/abstract
  19. ↑ Quetiapine in the treatment of psychosis in Parkinson’s disease | http://tan.sagepub.com/content/3/6/339
  20. ↑ Taylor, D; Carol, P; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 9780470979693.
  21. ↑ Safety of Low Doses of Quetiapine When Used for Insomnia | http://aop.sagepub.com/content/46/5/718
  22. ↑ Off-Label Use of Atypical Antipsychotics: An Update [Internet] | http://www.ncbi.nlm.nih.gov/pubmed/22132426
  23. ↑ Journal of Child and Adolescent Psychopharmacology | http://online.liebertpub.com/doi/abs/10.1089/104454603322572624
  24. ↑ Oliver Sacks "Musicophilia" Knopf NY 2007 P.67
  25. ↑ Treatment of sleep dysfunction and psychiatric disorders | http://link.springer.com/article/10.1007%2Fs11940-006-0026-6
  26. ↑ Questions loom over drug for sleepless vets | http://www.marinecorpstimes.com/article/20100830/NEWS/8300315/Questions-loom-over-drug-for-sleepless-vets
  27. ↑ Heart Warning Added to Label on Popular Antipsychotic Drug | http://www.nytimes.com/2011/07/19/health/19drug.html?_r=3&
  28. ↑ Seroquel linked to Deadly Side Effects | http://www.defendingtheconsumer.com/drug-injury-lawyer/seroquel-linked-to-deadly-side-effects/
  29. ↑ Seroquel | http://www.resource4thepeople.com/defectivedrugs/seroquel.html
  30. ↑ Tardive dyskinesia and new antipsychotics | http://journals.lww.com/co-psychiatry/pages/articleviewer.aspx?year=2008&issue=03000&article=00012&type=abstract
  31. ↑ Tardive dyskinesia and new antipsychotics | http://journals.lww.com/co-psychiatry/pages/articleviewer.aspx?year=2008&issue=03000&article=00012&type=abstract
  32. ↑ Tardive Dyskinesia | http://link.springer.com/article/10.1007%2Fs11940-011-0117-x
  33. ↑ Antipsychotic-Induced Weight Gain: A Comprehensive Research Synthesis Am J Psychiatry 1999;156:1686-1696.
  34. ↑ Quetiapine: Relatively safe in overdose? | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755169/
  35. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1355–1357.
  36. ↑ Quetiapine Discontinuation Syndrome | http://ajp.psychiatryonline.org/article.aspx?articleID=177544
  37. ↑ Reversible withdrawal dyskinesia associated with quetiapine | http://onlinelibrary.wiley.com/doi/10.1002/mds.20427/abstract
  38. ↑ http://reference.medscape.com/drug/seroquel-xr-quetiapine-342984#10
  39. ↑ http://www.medicines.org.uk/emc/medicine/26575/SPC/Quetiapine+25+mg+film-coated+tablets/
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