Misplaced Pages

Latest revision as of 23:29, 8 December 2024

Quetiapine

Clinical data
Pronunciation	/kwɪˈtaɪ.əpiːn/ kwi-TY-ə-peen
Trade names	Seroquel, Seroquel Xr, others
AHFS/Drugs.com	Monograph
MedlinePlus	a698019
License data	US DailyMed: Quetiapine
Pregnancy category	AU: B3
Routes of administration	By mouth
Drug class	Atypical antipsychotic
ATC code	N05AH04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances) CA: ℞-only UK: POM (Prescription only) US: WARNINGRx-only
Pharmacokinetic data
Bioavailability	100%
Protein binding	83%
Metabolism	Liver via CYP3A4-catalysed sulfoxidation to its active metabolite norquetiapine (N-desalkylquetiapine)
Elimination half-life	7 hours (parent compound); 9–12 hours (active metabolite, norquetiapine)
Excretion	Kidney (73%), feces (20%)
Identifiers
IUPAC name 2-(2-(4-Dibenzothiazepine-11-yl-1-piperazinyl)ethoxy)ethanol
CAS Number	111974-69-7
PubChem CID	5002
IUPHAR/BPS	50
DrugBank	DB01224
ChemSpider	4827
UNII	BGL0JSY5SI
KEGG	D08456
ChEBI	CHEBI:8707
ChEMBL	ChEMBL716
CompTox Dashboard (EPA)	DTXSID9023546
ECHA InfoCard	100.131.193
Chemical and physical data
Formula	C21H25N3O2S
Molar mass	383.51 g·mol
3D model (JSmol)	Interactive image
Solubility in water	3.29 mg/mL (20 °C)
SMILES N\1=C(\c3c(Sc2c/1cccc2)cccc3)N4CCN(CCOCCO)CC4
InChI InChI=1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2 Key:URKOMYMAXPYINW-UHFFFAOYSA-N
(verify)

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its tranquillizing effects, the benefits of such use may not outweigh the risk of undesirable side effects. It is taken orally.

Common side effects include sedation, fatigue, weight gain, constipation, and dry mouth. Other side effects include low blood pressure with standing, seizures, a prolonged erection, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome. In older people with dementia, its use increases the risk of death. Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth. Quetiapine is believed to work by blocking a number of receptors, including those for serotonin and dopamine.

Quetiapine was developed in 1985 and was approved for medical use in the United States in 1997. It is available as a generic medication. In 2022, it was the 82nd most commonly prescribed medication in the United States, with more than 8 million prescriptions. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Quetiapine is primarily used to treat schizophrenia or bipolar disorder. Quetiapine targets both positive and negative symptoms of schizophrenia.

Schizophrenia

A 2013 Cochrane review compared quetiapine to typical antipsychotics:

In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13–16% more effective than ziprasidone, chlorpromazine, and asenapine and approximately as effective as haloperidol and aripiprazole.

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.

It is debatable whether, as a class, typical or atypical antipsychotics are more effective. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.

A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than olanzapine and risperidone; produce fewer movement related side effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine; and produce weight gain similar to risperidone, clozapine and aripiprazole. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity and white blood cell count at a rate similar to first generation antipsychotics.

Bipolar disorder

In those with bipolar disorder, quetiapine is used to treat depressive episodes; acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium; valproate or lamotrigine); acute mixed episodes; and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).

Major depressive disorder

Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD). However, sedation is often an undesirable side effect.

In the United States, the United Kingdom and Australia (while not subsidised by the Australian Pharmaceutical Benefits Scheme for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD.

Alzheimer's disease

Quetiapine does not decrease agitation among people with Alzheimer's disease. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.

Insomnia

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. A 2022 network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine did not demonstrate any short-term benefits in sleep quality. Quetiapine, specifically, had an effect size (standardized mean difference) against placebo for treatment of insomnia of 0.05 (95% CITooltip confidence interval –1.21 to 1.11) at 4 weeks of treatment, with the certainty of evidence rated as very low. Doses of quetiapine used for insomnia have ranged from 12.5 to 800 mg, with low doses of 25 to 200 mg being the most typical. Regardless of the dose used, some of the more serious adverse effects may still possibly occur at the lower dosing ranges, such as dyslipidemia and neutropenia. These safety concerns at low doses are corroborated by Danish observational studies that showed use of specifically low-dose quetiapine (prescriptions filled for tablet strengths >50 mg were excluded) was associated with an increased risk of major cardiovascular events as compared to use of Z-drugs, with most of the risk being driven by cardiovascular death. Laboratory data from an unpublished analysis of the same cohort also support the lack of dose-dependency of metabolic side effects, as new use of low-dose quetiapine was associated with a risk of increased fasting triglycerides at 1-year follow-up.

Others

It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome, musical hallucinations and anxiety disorders.

Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their relatively 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.

Adverse effects

Sources for incidence lists:

Very common (>10% incidence) adverse effects

• Dry mouth
• Dizziness
• Headache
• Somnolence (drowsiness; of 15 antipsychotics quetiapine causes the 5th most sedation. Extended release (XR) formulations tend to produce less sedation, dose-by-dose, than the immediate release formulations.)

Common (1–10% incidence) adverse effects

• High blood pressure
• Orthostatic hypotension
• High pulse rate
• High blood cholesterol
• Elevated serum triglycerides
• Abdominal pain
• Constipation
• Increased appetite
• Vomiting
• Increased liver enzymes
• Backache
• Asthenia
• Insomnia
• Lethargy
• Tremor
• Agitation
• Nasal congestion
• Pharyngitis
• Fatigue
• Pain
• Dyspepsia (Indigestion)
• Peripheral oedema
• Dysphagia

• Extrapyramidal disease: Quetiapine and clozapine are noted for their relative lack of extrapyramidal side effects.
• Weight gain: SMD 0.43 kg when compared to placebo. Produces roughly as much weight gain as risperidone, less weight gain than clozapine, olanzapine and zotepine and more weight gain than ziprasidone, lurasidone, aripiprazole and asenapine. As with many other atypical antipsychotics, this action is likely due to its actions at the H₁ histamine receptor and 5-HT_2C receptor.

Rare (<1% incidence) adverse effects

• Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17)
• Sudden cardiac death
• Syncope
• Diabetic ketoacidosis
• Restless legs syndrome
• Hyponatraemia, low blood sodium.
• Jaundice, yellowing of the eyes, skin and mucous membranes due to an impaired ability of the body to clear bilirubin, a by product of haem breakdown.
• Pancreatitis, pancreas swelling.
• Agranulocytosis, a potentially fatal drop in white blood cell count.
• Leukopenia, a drop in white blood cell count, not as severe as agranulocytosis.
• Neutropenia, a drop in neutrophils, the cell of the immune cells that defends the body against bacterial infections.
• Eosinophilia
• Anaphylaxis, a potentially fatal allergic reaction.
• Seizure
• Hypothyroidism, underactive thyroid gland.
• Myocarditis, swelling of the myocardium.
• Cardiomyopathy
• Hepatitis, swelling of the liver.
• Suicidal ideation
• Priapism. A prolonged and painful erection.
• Stevens–Johnson syndrome. A potentially fatal skin reaction.

• Neuroleptic malignant syndrome a rare and potentially fatal complication of antipsychotic drug treatment. It is characterised by the following symptoms: tremor, rigidity, hyperthermia, tachycardia, mental status changes (e.g. confusion), etc.
• Tardive dyskinesia. A rare and often irreversible neurological condition characterised by involuntary movements of the face, tongue, lips and rest of the body. Most commonly occurs after prolonged treatment with antipsychotics. It is believed to be particularly uncommon with atypical antipsychotics, especially quetiapine and clozapine

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

Weight gain can be a problem for some, with quetiapine causing more weight gain than fluphenazine, haloperidol, loxapine, molindone, olanzapine, pimozide, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone, but less than chlorpromazine, clozapine, perphenazine, and sertindole.

As with some other anti-psychotics, quetiapine may lower the seizure threshold, and should be taken with caution in combination with drugs such as bupropion.

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.

There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.

Pregnancy and lactation

Placental exposure is least for quetiapine compared to other atypical antipsychotics. The evidence is insufficient to rule out any risk to the foetus but available data suggests it is unlikely to result in any major foetal malformations. It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.

Abuse potential

In contrast to most other antipsychotic drugs, which tend to be somewhat aversive and often show problems with patient compliance with prescribed medication regimes, quetiapine is sometimes associated with drug misuse and abuse potential, for its hypnotic and sedative effects. It has a limited potential for misuse, usually only in individuals with a history of polysubstance abuse and/or mental illness, and especially in those incarcerated in prisons or secure psychiatric facilities where access to alternative intoxicants is more limited. To a significantly greater extent than other atypical antipsychotic drugs, quetiapine was found to be associated with drug-seeking behaviors, and to have standardised street prices and slang terms associated with it, either by itself or in combination with other drugs (such as "Q-ball" for the intravenous injection of quetiapine mixed with cocaine). The pharmacological basis for this distinction from other second generation antipsychotic drugs is unclear, though it has been suggested that quetiapine's comparatively lower dopamine receptor affinity and strong antihistamine activity might mean it could be regarded as more similar to sedating antihistamines in this context. While these issues have not been regarded as sufficient cause for placing quetiapine under increased legal controls, prescribers have been urged to show caution when prescribing quetiapine to individuals with characteristics that might place them at increased risk for drug misuse.

Overdose

Most instances of acute overdosage result in only sedation, hypotension and tachycardia, but cardiac arrhythmia, 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. Non-toxic levels in postmortem blood extend to around 0.8 mg/kg, but toxic levels in postmortem blood can begin at 0.35 mg/kg.

Pharmacology

Pharmacodynamics

Quetiapine has the following pharmacological actions:

• Dopamine D₁, D₂, D₃, D₄, and D₅ receptor antagonist
• Serotonin 5-HT_1A receptor partial agonist, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₃, 5-HT₆, and 5-HT₇ receptor antagonist, and 5-HT_1B, 5-HT_1D, 5-HT_1E, and 5-HT_1F receptor ligand
• α₁- and α₂-adrenergic receptor antagonist
• Histamine H₁ receptor antagonist
• Muscarinic acetylcholine receptor antagonist

This means quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties. Quetiapine binds strongly to serotonin receptors; the drug acts as a partial agonist at 5-HT_1A receptors and as an antagonist to all other serotonin receptors it has affinity for. Serial PET scans evaluating the D₂ receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D₂ receptor. 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. Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters.

At very low doses, quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α₁-adrenergic blocker. When the dose is increased, quetiapine activates the adrenergic system and binds strongly to serotonin receptors and autoreceptors. At high doses, quetiapine starts blocking significant amounts of dopamine receptors. Due to the drug's sedating H₁ activity, it is often prescribed at low doses for insomnia. While some feel that low doses of drugs with antihistamine effects like quetiapine and mirtazapine are safer than drugs associated with physical dependency or other risk factors, concern has been raised by some professionals that off-label prescribing has become too widespread due to underappreciated hazards.

When treating schizophrenia, antagonism of D₂ receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5-HT_2A receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes. Quetiapine has fewer extrapyramidal side effects and is less likely to cause hyperprolactinemia when compared to other drugs used to treat schizophrenia, so is used as a first line treatment.

Pharmacokinetics

Peak levels of quetiapine occur 1.5 hours after a dose. The plasma protein binding of quetiapine is 83%. The major active metabolite of quetiapine is norquetiapine (N-desalkylquetiapine). Quetiapine has an elimination half-life of 6 or 7 hours. Its metabolite, norquetiapine, has a half-life of 9 to 12 hours. Quetiapine is excreted primarily via the kidneys (73%) and in feces (20%) after hepatic metabolism, the remainder (1%) is excreted as the drug in its unmetabolized form.

Chemistry

Quetiapine is a tetracyclic compound and is closely related structurally to clozapine, olanzapine, loxapine, and other tetracyclic antipsychotics.

Synthesis

The synthesis of quetiapine begins with a dibenzothiazepinone. The lactam is first treated with phosphoryl chloride to produce a dibenzothiazepine. A nucleophilic substitution is used to introduce the sidechain.

History

Sustained-release

AstraZeneca 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.

In May 2007, the US FDA approved Seroquel XR for acute treatment of schizophrenia. During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007. However, Seroquel XR has become available in U.S. pharmacies only after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on 16 November 2007. The company has not provided a reason for the delay of Seroquel XR's launch.

Health Canada approved sale of Seroquel XR on 27 September 2007.

In October 2008, the FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania.

In December 2008, Biovail announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine. Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR.

In December 2008, AstraZeneca notified shareholders that the FDA had asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression.

Society and culture

Regulatory status

In the United States, the Food and Drug Administration (FDA) has approved quetiapine for the treatment of schizophrenia and of acute manic episodes associated with bipolar disorder (bipolar mania) and for treatment of bipolar depression. In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.

Quetiapine received its initial approval from the US FDA for the treatment of schizophrenia in 1997. In 2004, it received its second indication for the treatment of mania-associated bipolar disorder. In 2007 and 2008, studies were conducted on quetiapine's efficacy in treating generalized anxiety disorder and major depression.

Patent protection for the product ended in 2012; however, in a number of regions, the long-acting version remained under patent until 2017.

Lawsuits

In April 2010, the U. S. Department of Justice fined AstraZeneca $520 million for the company's aggressive marketing of Seroquel for off-label uses. According to the Department of Justice, "the company recruited doctors to serve as authors of articles that were ghostwritten by medical literature companies and about studies the doctors in question did not conduct. AstraZeneca then used those studies and articles as the basis for promotional messages about unapproved uses of Seroquel."

Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, diabetes.

Approximately 10,000 lawsuits have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths.

Controversy

In 2004, a young man named Dan Markingson committed suicide in a controversial Seroquel clinical trial at the University of Minnesota while under an involuntary commitment order. A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations.

Nurofen Plus tampering case

In August 2011, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a class-4 drug alert following reports that some batches of Nurofen plus contained Seroquel XL tablets instead.

Following the issue of the Class-4 Drug Alert, Reckitt Benckiser (UK) Ltd received further reports of rogue blister strips in cartons of two additional batches of Nurofen Plus tablets. One of the new batches contained Seroquel XL 50 mg tablets and one contained the Pfizer product Neurontin 100 mg capsules.

Following discussions with the MHRA's Defective Medicines Report Centre (DMRC), Reckitt Benckiser (UK) Ltd decided to recall all remaining unexpired stock of Nurofen Plus tablets in any pack size, leading to a Class-1 Drug Alert. The contamination was later traced to in-store tampering by a customer.

References

1. "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
2. "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
3. Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
4. ^ "Seroquel- quetiapine tablet, film coated". DailyMed. 27 January 2022. Retrieved 22 September 2024.
5. "Seroquel Xr- quetiapine tablet, extended release". DailyMed. 27 January 2022. Retrieved 22 September 2024.
6. ^ "quetiapine (Rx) - Seroquel, Seroquel XR". Medscape Reference. WebMD. Archived from the original on 20 October 2013. Retrieved 11 October 2013.
7. ^ "Quetiapine 25 mg film-coated tablets - Summary of Product Characteristics". electronic Medicines Compendium. Sandoz. January 2013. Archived from the original on 20 October 2013. Retrieved 20 October 2013.
8. ^ Truven Health Analytics, Inc. DrugPoint System (Internet) . Greenwood Village, CO: Thomsen Healthcare; 2013.
9. ^ "Quetiapine fumarate tablet". DailyMed. Ascend Laboratories, LLC. October 2013. Archived from the original on 2 December 2013. Retrieved 26 November 2013.
10. ^ Brunton L, Chabner B, Knollman B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). McGraw Hill Professional. ISBN 978-0071624428.
11. ^ "Quetiapine Fumarate". The American Society of Health-System Pharmacists. Archived from the original on 29 August 2017. Retrieved 26 March 2017.
12. ^ Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S (December 2010). "Second-generation antipsychotics for major depressive disorder and dysthymia". The Cochrane Database of Systematic Reviews (12): CD008121. doi:10.1002/14651858.CD008121.pub2. PMID 21154393.
13. Anderson SL, Vande Griend JP (March 2014). "Quetiapine for insomnia: A review of the literature" (PDF). American Journal of Health-System Pharmacy. 71 (5): 394–402. doi:10.2146/ajhp130221. PMID 24534594. S2CID 207292819. Archived from the original (PDF) on 19 February 2020.
14. Riedel M, Müller N, Strassnig M, Spellmann I, Severus E, Möller HJ (April 2007). "Quetiapine in the treatment of schizophrenia and related disorders". Neuropsychiatric Disease and Treatment. 3 (2): 219–235. doi:10.2147/nedt.2007.3.2.219. PMC 2654633. PMID 19300555.
15. British national formulary: BNF 74 (74 ed.). British Medical Association. 2017. p. 383. ISBN 978-0857112989.
16. "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
17. "Quetiapine Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
18. World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
19. "quetiapine-fumarate". The American Society of Health-System Pharmacists. Archived from the original on 10 February 2011. Retrieved 3 April 2011.
20. ^ Dev V, Raniwalla J (October 2000). "Quetiapine: a review of its safety in the management of schizophrenia". Drug Safety. 23 (4): 295–307. doi:10.2165/00002018-200023040-00003. PMID 11051217.
21. ^ Suttajit S, Srisurapanont M, Xia J, Suttajit S, Maneeton B, Maneeton N (May 2013). "Quetiapine versus typical antipsychotic medications for schizophrenia". The Cochrane Database of Systematic Reviews. 5 (5): CD007815. doi:10.1002/14651858.CD007815.pub2. PMID 23728667. Archived from the original on 21 April 2016.
22. ^ Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. S2CID 32085212.
23. ^ Srisurapanont M, Maneeton B, Maneeton N (2004). Srisurapanont M (ed.). "Quetiapine for schizophrenia". The Cochrane Database of Systematic Reviews. 2004 (2): CD000967. doi:10.1002/14651858.CD000967.pub2. PMC 7032613. PMID 15106155.
24. Kane JM, Correll CU (2010). "Pharmacologic treatment of schizophrenia". Dialogues in Clinical Neuroscience. 12 (3): 345–357. doi:10.31887/DCNS.2010.12.3/jkane. PMC 3085113. PMID 20954430.
25. Schultz SH, North SW, Shields CG (June 2007). "Schizophrenia: a review". American Family Physician. 75 (12): 1821–1829. PMID 17619525.
26. Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S (November 2013). "Quetiapine versus other atypical antipsychotics for schizophrenia". The Cochrane Database of Systematic Reviews. 11 (11): CD006625. doi:10.1002/14651858.CD006625.pub3. PMC 4167871. PMID 24249315.
27. Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC (2013). "Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes". PLOS Medicine. 10 (3): e1001403. doi:10.1371/journal.pmed.1001403. PMC 3595214. PMID 23554581.
28. ^ British National Formulary (BNF) 65. London, UK: Pharmaceutical Press. 2013. p. 235. ISBN 9780857110848.
29. ^ Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
30. Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, et al. (April 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. PMC 556156. PMID 15722369.
31. ^ Coe HV, Hong IS (May 2012). "Safety of low doses of quetiapine when used for insomnia". The Annals of Pharmacotherapy. 46 (5): 718–722. doi:10.1345/aph.1Q697. PMID 22510671. S2CID 9888209.
32. ^ Anderson SL, Vande Griend JP (March 2014). "Quetiapine for insomnia: A review of the literature". American Journal of Health-System Pharmacy. 71 (5): 394–402. doi:10.2146/ajhp130221. PMID 24534594.
33. Modesto-Lowe V, Harabasz AK, Walker SA (May 2021). "Quetiapine for primary insomnia: Consider the risks". Cleveland Clinic Journal of Medicine. 88 (5): 286–294. doi:10.3949/ccjm.88a.20031. PMID 33941603.
34. Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, et al. (September 2011). Off-Label Use of Atypical Antipsychotics: An Update (Report). PMID 22132426.
35. Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, et al. (2011). Off-Label Use of Atypical Antipsychotics: An Update. Comparative Effectiveness Reviews, No. 43. Rockville: Agency for Healthcare Research and Quality. PMID 22973576.
36. Coe HV, Hong IS (May 2012). "Safety of low doses of quetiapine when used for insomnia". The Annals of Pharmacotherapy. 46 (5): 718–722. doi:10.1345/aph.1Q697. PMID 22510671. S2CID 9888209.
37. De Crescenzo F, D'Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, et al. (July 2022). "Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis". Lancet. 400 (10347): 170–184. doi:10.1016/S0140-6736(22)00878-9. hdl:11380/1288245. PMID 35843245. S2CID 250536370.
38. Wine JN, Sanda C, Caballero J (April 2009). "Effects of quetiapine on sleep in nonpsychiatric and psychiatric conditions". The Annals of Pharmacotherapy. 43 (4): 707–713. doi:10.1345/aph.1L320. PMID 19299326. S2CID 207263320.
39. Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, et al. (January 2020). "Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis". The Lancet. Psychiatry. 7 (1): 64–77. doi:10.1016/s2215-0366(19)30416-x. PMC 7029416. PMID 31860457.
40. Yoshida K, Takeuchi H (March 2021). "Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia". Behavioural Brain Research. 402: 113098. doi:10.1016/j.bbr.2020.113098. PMID 33417992. S2CID 230507941.
41. Højlund M, Andersen K, Ernst MT, Correll CU, Hallas J (October 2022). "Use of low-dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator-controlled cohort study". World Psychiatry. 21 (3): 444–451. doi:10.1002/wps.21010. PMC 9453914. PMID 36073694.
42. Højlund M (12 September 2022). Low-dose Quetiapine: Utilization and Cardiometabolic Risk (Ph.D. thesis). University of Southern Denmark. doi:10.21996/mr3m-1783.
43. Mukaddes NM, Abali O (2003). "Quetiapine treatment of children and adolescents with Tourette's disorder". Journal of Child and Adolescent Psychopharmacology. 13 (3): 295–299. doi:10.1089/104454603322572624. PMID 14642017.
44. Oliver Sacks "Musicophilia" Knopf NY 2007 P.67
45. Becker PM (September 2006). "Treatment of sleep dysfunction and psychiatric disorders". Current Treatment Options in Neurology. 8 (5): 367–375. doi:10.1007/s11940-006-0026-6. PMID 16901376. S2CID 34246401.
46. Kyle K, Bronstein JM (June 2020). "Treatment of psychosis in Parkinson's disease and dementia with Lewy Bodies: A review". Parkinsonism & Related Disorders. 75: 55–62. doi:10.1016/j.parkreldis.2020.05.026. PMID 32480308. S2CID 219168745. In clinical practice, quetiapine is more readily used than clozapine, given its improved side effect profile compared to clozapine. Despite frequent use in clinical practice, its efficacy in PDP is less clear. ... The quetiapine evidence base is thus ambiguous, lacking consistent support from RCTs in PDP. In DLB there is reliance upon retrospective studies, with the inherent limitations therein. As with clozapine, sedation and orthostasis can be limiting factors. In clinical practice, despite the paucity of consistent evidence, quetiapine has been the first line antipsychotic therapy due to its side effect profile and lower neuroleptic sensitivity risk.
47. Shotbolt P, Samuel M, David A (November 2010). "Quetiapine in the treatment of psychosis in Parkinson's disease". Therapeutic Advances in Neurological Disorders. 3 (6): 339–350. doi:10.1177/1756285610389656. PMC 3002640. PMID 21179595.
48. ^ Taylor D, Carol P, Shitij K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 9780470979693.
49. ^ "PRODUCT INFORMATION STADA(TM) Quetiapine (quetiapine fumarate Tablets 25 mg, 100 mg, 200 mg, 300 mg)". TGA eBusiness Services. STADA Pharmaceuticals Australia Pty Limited. 30 November 2012. Archived from the original on 27 March 2017. Retrieved 19 September 2013.
50. ^ Correll CU, Schenk EM (March 2008). "Tardive dyskinesia and new antipsychotics". Current Opinion in Psychiatry. 21 (2): 151–156. doi:10.1097/YCO.0b013e3282f53132. PMID 18332662. S2CID 37288246.
51. Aia PG, Revuelta GJ, Cloud LJ, Factor SA (June 2011). "Tardive dyskinesia". Current Treatment Options in Neurology. 13 (3): 231–241. doi:10.1007/s11940-011-0117-x. PMID 21365202. S2CID 24308129.
52. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, et al. (November 1999). "Antipsychotic-induced weight gain: a comprehensive research synthesis". The American Journal of Psychiatry. 156 (11): 1686–96. doi:10.1176/ajp.156.11.1686. PMID 10553730. S2CID 38635470.
53. "Seroquel Prescribing Information". www.astrazeneca-us.com.
54. Joint Formulary Committee BMJ, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 978-0-85369-845-6. 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.
55. ^ Haddad PM, Dursun S, Deakin B (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. pp. 207–216. ISBN 9780198527480.
56. Moncrieff J (July 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica. 114 (1): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655. S2CID 6267180.
57. Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013). Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85. ISBN 9788847026797.
58. Klein L, Bangh S, Cole JB (February 2017). "Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics". The Western Journal of Emergency Medicine. 18 (2): 243–250. doi:10.5811/westjem.2016.10.32322. PMC 5305132. PMID 28210359.
59. Kim S, Lee G, Kim E, Jung H, Chang J (2017). "Quetiapine Misuse and Abuse: Is it an Atypical Paradigm of Drug Seeking Behavior?". Journal of Research in Pharmacy Practice. 6 (1): 12–15. doi:10.4103/2279-042X.200987. PMC 5348850. PMID 28331860.
60. Chiappini S, Schifano F (February 2018). "Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of the European Medicines Agency/European Medicines Agency Adverse Drug Reactions' Database". Journal of Clinical Psychopharmacology. 38 (1): 72–79. doi:10.1097/JCP.0000000000000814. hdl:2299/19835. PMID 29210868. S2CID 3292900.
61. Evoy KE, Teng C, Encarnacion VG, Frescas B, Hakim J, Saklad S, et al. (2019). "Comparison of Quetiapine Abuse and Misuse Reports to the FDA Adverse Event Reporting System With Other Second-Generation Antipsychotics". Substance Abuse. 13: 1178221819844205. doi:10.1177/1178221819844205. PMC 6495438. PMID 31068753.
62. Vento AE, Kotzalidis GD, Cacciotti M, Papanti GD, Orsolini L, Rapinesi C, et al. (2020). "Quetiapine Abuse Fourteen Years Later: Where Are We Now? A Systematic Review". Substance Use & Misuse. 55 (2): 304–313. doi:10.1080/10826084.2019.1668013. PMID 31573374. S2CID 203621793.
63. Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1355–1357.
64. Skov L, Johansen SS, Linnet K (January 2015). "Postmortem femoral blood reference concentrations of aripiprazole, chlorprothixene, and quetiapine". Journal of Analytical Toxicology. 39 (1): 41–44. doi:10.1093/jat/bku121. PMID 25342720.
65. Skov L, Johansen SS, Linnet K (September 2015). "Postmortem Quetiapine Reference Concentrations in Brain and Blood". Journal of Analytical Toxicology. 39 (7): 557–561. doi:10.1093/jat/bkv072. PMID 26159868.
66. Roth BL, Driscol J. "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
67. ^ Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–2312. doi:10.1038/sj.npp.1301646. PMID 18059438.
68. ^ Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801. S2CID 12028979.
69. "Seroquel (quietapine fumarate) tablets" (PDF). AstraZeneca. 276521. Archived from the original (PDF) on 14 April 2008.
70. ^ 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.
71. Miyamoto SE, Duncan GE, Goff DC, Lieberman JA (2002). "Therapeutics of schizophrenia". In Davis KL, Charney D, Coyle JT, Nemeroff C (eds.). Neuropsychopharmacology: the fifth generation of progress. American College of Neuropsychopharmacology. ISBN 978-0-7817-2837-9.
72. "Seroquel Official FDA information, side effects and uses". Drugs.com. Archived from the original on 4 June 2012. Retrieved 9 July 2012.
73. National Institute of Mental Health. PDSD Ki Database (Internet) . Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: "...list shows the top 100 Receptors/Targets in Ki". Archived from the original on 8 November 2013. Retrieved 5 July 2013.
74. Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–2312. doi:10.1038/sj.npp.1301646. PMID 18059438.
75. López-Muñoz F, Alamo C (September 2013). "Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders". Frontiers in Psychiatry. 4: 102. doi:10.3389/fpsyt.2013.00102. PMC 3770982. PMID 24062697.
76. Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, et al. (July 2008). "Anticholinergic activity of 107 medications commonly used by older adults". Journal of the American Geriatrics Society. 56 (7): 1333–1341. doi:10.1111/j.1532-5415.2008.01737.x. PMID 18510583. S2CID 11448976.
77. Guzman F. "Mechanism of action of quetiapine". Psychopharmacology Institute. Archived from the original on 11 August 2013. Retrieved 20 January 2013.
78. Kapur S, Seeman P (March 2001). "Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis". The American Journal of Psychiatry. 158 (3): 360–369. doi:10.1176/appi.ajp.158.3.360. PMID 11229973.
79. Seeman P (February 2002). "Atypical antipsychotics: mechanism of action". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 47 (1): 27–38. doi:10.1177/070674370204700106. PMID 11873706.
80. Gefvert O, Lundberg T, Wieselgren IM, Bergström M, Långström B, Wiesel F, et al. (April 2001). "D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study". European Neuropsychopharmacology. 11 (2): 105–110. doi:10.1016/S0924-977X(00)00133-4. PMID 11313155. S2CID 29460397.
81. "Drug Use Evaluation: Low Dose Quetiapine (Seroquel/Seroquel XR)" (PDF). Government Executive Media Group. Oregon State. Archived (PDF) from the original on 22 April 2016. Retrieved 20 January 2016.
82. ^ "Quetiapine". www.drugbank.ca. Retrieved 23 January 2019.
83. "Seroquel" (PDF). FDA. Retrieved 23 January 2019.
84. Nemeroff CB, Kinkead B, Goldstein J (2002). "Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing". The Journal of Clinical Psychiatry. 63 (Suppl 13): 5–11. PMID 12562141.
85. Kasper S, Müller-Spahn F (May 2000). "Review of quetiapine and its clinical applications in schizophrenia". Expert Opinion on Pharmacotherapy. 1 (4): 783–801. doi:10.1517/14656566.1.4.783. PMID 11249516. S2CID 22978385.
86. ^ "Seroquel" (PDF). FDA. Retrieved 23 January 2019.
87. Warawa, E. J.; Migler, B. M.; 1988, U.S. patent 4,879,288.
88. "AstraZeneca Submits an NDA For Sustained Release Formulation Seroquel XR. For the treatment of schizophrenia" (Press release). AstraZeneca. 18 July 2006. Archived from the original on 5 November 2006. Retrieved 1 January 2007.
89. "AstraZeneca Submits EU and Canadian Regulatory Filings for Sustained Release Formulation Seroquel XR for the Treatment of Schizophrenia" (Press release). AstraZeneca. 19 October 2006. Archived from the original on 7 November 2006. Retrieved 1 January 2007.
90. "FDA Approves AstraZeneca's Once-Daily Seroquel Xr Extended-Release Tablets For The Treatment Of Schizophrenia" (Press release). AstraZeneca. 18 May 2007. Archived from the original on 28 September 2007. Retrieved 2 August 2007.
91. "Second Quarter and Half Year Results 2007" (Press release). AstraZeneca. 26 July 2007. Archived from the original on 24 August 2007. Retrieved 2 August 2007.
92. "Seroquel XR Receives Approval from FDA for Maintenance Treatment of Schizophrenia" (Press release). AstraZeneca. 16 November 2007. Archived from the original on 4 December 2007. Retrieved 3 December 2007.
93. Notice of Compliance Information - Seroquel XR 27 September 2007, retrieved 3 December 2007
94. "Biovail Announces Filing of ANDA for Quetiapine XR Tablets" (Press release). Biovail. 1 December 2008. Archived from the original on 9 August 2007.
95. "AstraZeneca Receives FDA Complete Response Letter on Seroquel XR for Major Depressive Disorder" (Press release). AstraZeneca. 24 December 2008. Archived from the original on 26 October 2010. Retrieved 28 December 2008.
96. ^ "Pharmaceutical Giant AstraZeneca to Pay $520 Million for Off-label Drug Marketing". Justice news, US Department of Justice. 27 April 2010. Archived from the original on 13 July 2012. Retrieved 16 July 2012.
97. Guzman F. "Quetiapine Indications: FDA-Approved and Off-label Uses". Psychopharmacology Institute. Archived from the original on 22 January 2014. Retrieved 19 January 2013.
98. "QUETIAPINE FUMARATE". Electronic Orange Book. Food and Drug Administration. April 2007. Archived from the original on 5 January 2009. Retrieved 24 May 2007.
99. "AstraZeneca Receives FDA Approval for SEROQUEL in Bipolar Mania" (Press release). AstraZeneca. 13 January 2004. Archived from the original on 8 June 2011.
100. AstraZeneca (2013). "Pioneering science, life-changing medicines". www.sec.gov. Archived from the original on 6 March 2016. Retrieved 26 March 2017.
101. Knef A (2 August 2007). "Seroquel suit claims 'so much' is poured into marketing and away from research". The Madison / St. Clair Record. Archived from the original on 21 August 2008.
102. Milford P (11 March 2009). "AstraZeneca May Link Seroquel, Diabetes, Doctor Says". Bloomberg.com. Bloomberg L.P. Archived from the original on 24 September 2015.
103. "AstraZeneca wins bellwether Seroquel case". FiercePharma. 19 March 2010. Archived from the original on 14 March 2012. Retrieved 9 July 2012.
104. "AstraZeneca pays out million dollar damages". The Local. 9 August 2010. Archived from the original on 17 August 2010.
105. "Questions loom over drug for sleepless vets - Marine Corps News | News from Afghanistan & Iraq". Marine Corps Times. Archived from the original on 2 June 2013. Retrieved 9 July 2012.
106. Wilson D (19 July 2011). "Heart Warning Added to Label on Popular Antipsychotic Drug". NyTimes. Archived from the original on 2 July 2012. Retrieved 9 July 2012.
107. Elliott C (September–October 2010). "The Deadly Corruption of Clinical Trials". Mother Jones. Archived from the original on 17 November 2012. Retrieved 2 December 2012.
108. Couzin-Frankel J (7 December 2010). "Minnesota bioethicists critique their university". Science. Archived from the original on 21 February 2013. Retrieved 2 December 2012.
109. "Press release, 25 August 2011" (Press release). MHRA. Archived from the original on 19 March 2012. Retrieved 9 July 2012.
110. "Drug Alerts". MHRA. Archived from the original on 19 March 2012. Retrieved 9 July 2012.
111. "Nurofen Plus tampering: Christopher McGuire jailed". BBC News. 28 May 2012. Archived from the original on 14 June 2012. Retrieved 9 July 2012.

External links