Quetiapine

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Summary sheet: Quetiapine
Quetiapine
Molecular structure of Quetiapine.
Quetiapine.svg
Chemical Nomenclature
Common names Quetiapine, Seroquel
Substitutive name Xeroquel, Ketipinor
Systematic name 2-(2-(4-dibenzo[b,f] [1,4]thiazepine- 11-yl- 1-piperazinyl)ethoxy) ethanol
Class Membership
Psychoactive class Antipsychotic
Chemical class Dibenzothiazepine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 15 - 25 mg
Light 25 - 50 mg
Common 50 - 150 mg
Strong 150 - 300 mg
Heavy 300 mg +
Duration
Total 4 - 8 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Quetiapine (branded as Seroquel, Xeroquel, and 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 of Seroquel 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 name brand versions of quetiapine, such as Quepin, Seroquel and Ketipinor.[7]

Chemistry

Quetiapine is an atypical antipsychotic drug and dibenzothiazepine derivative. Quetiapine contains a thiazepine ring, a seven-membered ring containing one sulfur and one nitrogen group, located at R1 and R4 respectively. This ring is fused to two benzene rings, thus forming a dibenzothiazepine moiety. Dibenzothiazepine is connected at R11 to the nitrogen group of a piperazine ring at R4.

Piperazine is a six-member unsaturated ring with two nitrogen constituents in the 1,4 positions. This ring is connected at its second nitrogen group to an ethoxyethanol chain. It is connected to R2 of an ethane chain through an oxygen bridge to an ethanol group. This forms the structure of quetiapine.

It is commonly synthesized by nucleophilic substitution to combine the dibenzothiazepine core with the rest of the structure. Quetiapine is present in its pill form as a fumarate salt.

Pharmacology

Quetiapine is a powerful dopaminergic, serotonergic, and adrenergic antagonist, as well as 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 within the mesolimbic pathway.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.

Physical effects
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Cognitive effects
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After effects
Aftereffects (3).svg


Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

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 depressive 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] It is particularly useful as a tool for forced sedation during bad trips or prolonged unwanted stimulation.

Toxicity and harm potential

Quetiapine likely has a low toxicity relative to dose. 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]

It is strongly recommended that one use harm reduction practices when using this drug.

Lethal dosage

Compared to other antipsychotics, quetiapine has been reported to be relatively safer in overdose.[34] Most instances of acute overdoses 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

Quitiapine is moderately physically and psychologically addictive.

Tolerance will develop to the antipsychotic effects and within a week of continuous use. The tolerance to the amount of sedation will be the most noticeable. After cessation, the tolerance returns to baseline in 7 - 14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.

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]

Legal issues

  • 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: It is available by prescription only and unscheduled.
  • France: It is available by prescription only and unscheduled.

See also

External links

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. US Patent & Trademark Office, Patent Full Text and Image Database (1989) | 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. US Patent & Trademark Office, Patent Full Text and Image Database (1989) | 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. Phillip Moeller (2011) 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. Quepin Tablets (Specifar) (2010) | 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 (ScienceDirect) | 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] (PubMed.gov / NCBI) | 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? (PubMed.gov / NCBI) | 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/