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Quetiapine

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Quetiapine (Template:IPAc-en Template:Respell), sold under the brand name Seroquel among others, is an atypical antipsychotic medication used in the treatment of schizophrenia, bipolar disorder, bipolar depression, and major depressive disorder.<ref name=AHFS2017>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=Cochrane2010>Template:Cite journal</ref> Despite being widely prescribed as a sleep aid due to its tranquillizing effects, the benefits of such use may not outweigh the risk of undesirable side effects.<ref>Template:Cite journal</ref> It is taken orally.<ref name=AHFS2017/>

Common side effects include sedation, fatigue, weight gain, constipation, and dry mouth.<ref name=AHFS2017/> Other side effects include low blood pressure with standing, seizures, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome.<ref name=AHFS2017/> In older people with dementia, its use increases the risk of death.<ref name=AHFS2017/> Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth.<ref name=AHFS2017/> Quetiapine is believed to work by blocking a number of receptors, including those for serotonin and dopamine.<ref name=AHFS2017/>

Quetiapine was developed in 1985 and was approved for medical use in the United States in 1997.<ref name="dailymed PI" /><ref name=AHFS2017/><ref>Template:Cite journal</ref> It is available as a generic medication.<ref name=BNF74>Template:Cite book</ref> In 2022, it was the most prescribed antipsychotic and 82nd most commonly prescribed medication in the United States, with more than 8Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref>

The drug is typically among two antipsychotics (the other being olanzapine) to have superior efficacy for the treatment of bipolar disorder. Quetiapine is currently one of only two antipsychotics (the other of which is cariprazine) that produce equal efficacy as a standalone therapy for mixed manic-depressive mood swings as it is when used in combination with an SSRI antidepressant. However, quetiapine is less potent than clozapine, amisulpride, olanzapine, risperidone, and paliperidone, respectively, in alleviating psychotic symptoms or treating schizophrenia.

Medical usesEdit

File:Seroquel-25mg.jpg
Quetiapine (Seroquel) 25 mg tablets, next to US one-cent coin for comparison
File:SeroquelXR150.jpg
Seroquel XR 150 mg tablet box

Quetiapine is primarily used to treat schizophrenia or bipolar disorder.<ref name=AHFS>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Quetiapine targets both positive and negative symptoms of schizophrenia.<ref name="Quetiapine">Template:Cite journal</ref>

SchizophreniaEdit

A 2013 Cochrane review compared quetiapine to typical antipsychotics:

Quetiapine compared to typical antipsychotics for schizophrenia<ref name=Sut2013>Template:Cite journal</ref>
Summary
Quetiapine may not differ from typical antipsychotics in the treatment of positive symptoms, general psychopathology, and negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain.<ref name=Sut2013/>

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.<ref name=Lancet/>

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 name=Coch2004>Template:Cite journal</ref>

It is debatable whether, as a class, typical or atypical antipsychotics are more effective.<ref>Template:Cite journal</ref> Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages.<ref name=AFP07>Template:Cite journal</ref> While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.<ref name=Coch2004/>

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 decline in white blood cell count at a rate similar to first generation antipsychotics.<ref name="Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S 2013 CD006625">Template:Cite journal</ref>

Bipolar disorderEdit

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 disorderEdit

Quetiapine is effective when used by itself<ref name =Cochrane2010/> and when used along with other medications in major depressive disorder (MDD).<ref name =Cochrane2010/><ref>Template:Cite journal</ref> However, sedation is often an undesirable side effect.<ref name =Cochrane2010/>

In the United States,<ref name = "DD" /> the United Kingdom<ref name = "BNF 65" /> 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.<ref name = "AMH">Template:Cite book</ref>

Alzheimer's diseaseEdit

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.<ref name="Ballard Margallo-Lana Juszczak Douglas et al : Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial">Template:Cite journal</ref>

InsomniaEdit

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 name="pmid22510671">Template:Cite journal</ref><ref name="pmid24534594">Template:Cite journal</ref><ref name="pmid33941603">Template:Cite journal</ref><ref name="pmid22132426">Template:Cite report</ref><ref name="Off-Label Use">Template:Cite book</ref><ref>Template:Cite journal</ref> 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% Template:Abbrlink –1.21 to 1.11) at 4Template:Nbspweeks of treatment, with the certainty of evidence rated as very low.<ref>Template:Cite journal</ref> Doses of quetiapine used for insomnia have ranged from 12.5 to 800Template:Nbspmg, with low doses of 25 to 200Template:Nbspmg being the most typical.<ref name="pmid19299326">Template:Cite journal</ref><ref name="pmid22510671" /><ref name="pmid24534594" /> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite thesis</ref>

OthersEdit

It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome,<ref name="Mukaddes_2013">Template:Cite journal</ref> musical hallucinations<ref>Oliver Sacks "Musicophilia" Knopf NY 2007 P.67</ref> and anxiety disorders.<ref name="Becker : Treatment of sleep dysfunction and psychiatric disorders">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref> 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>Template:Cite journal</ref><ref name = Maudsley/>

Adverse effectsEdit

Sources for incidence lists:<ref name = Medscape /><ref name = "DD"/><ref name = "BNF 65">Template:Cite book</ref><ref name = AMH /><ref name = Maudsley>Template:Cite book</ref><ref name=TGA>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.)<ref name=Lancet>Template:Cite journal</ref>
Common (1–10% incidence) adverse effects

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Rare (<1% incidence) adverse effects

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  • 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<ref name="AMH"/>

Both typical and atypical antipsychotics can cause tardive dyskinesia.<ref name=TD08>Template:Cite journal</ref> According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%.<ref name=TD08/> Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.<ref>Template:Cite journal</ref>

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.<ref name="pmid10553730">Template:Cite journal</ref>

As with some other anti-psychotics, quetiapine may lower the seizure threshold,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and should be taken with caution in combination with drugs such as bupropion.

DiscontinuationEdit

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">Template:Cite book</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>Template:Cite book</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>Template:Cite journal</ref> It may also result in reoccurrence of the condition that is being treated.<ref>Template:Cite book</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>

Pregnancy and lactationEdit

Placental exposure is least for quetiapine compared to other atypical antipsychotics.<ref name = Maudsley/> 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.<ref name = EMC/><ref name = DM/><ref name = TGA/> It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.<ref name = EMC/><ref name = DM/><ref name = TGA/>

Abuse potentialEdit

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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

OverdoseEdit

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.<ref>Template:Cite book</ref> 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.<ref name="Skov 2015 41-44">Template:Cite journal</ref><ref name="Skov 2015 557-561">Template:Cite journal</ref>

PharmacologyEdit

PharmacodynamicsEdit

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Site Template:Abbr Template:Abbr Action Ref
Template:Abbrlink >10,000 927 Blocker <ref name="pmid18059438">Template:Cite journal</ref>
Template:Abbrlink >10,000 58 Blocker <ref name="pmid18059438" />
Template:Abbrlink >10,000 >10,000 Template:Abbr <ref name="pmid18059438" />
5-HT1A 320–432 45 Partial agonist <ref name="pmid18059438" /><ref name="pmid8935801">Template:Cite journal</ref>
5-HT1B 1,109–2,050 1,117 Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
5-HT1D >10,000 249 Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
5-HT1E 1,250–2,402 97 Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
5-HT1F 2,240 Template:Abbr Template:Abbr <ref name="pmid8935801" />
5-HT2A 96–101 48 Antagonist <ref name="pmid18059438" /><ref name="pmid8935801" />
5-HT2B Template:Abbr 14 Antagonist <ref name="pmid18059438" />
5-HT2C 2,502 107 Antagonist <ref name="pmid18059438" />
5-HT3 >10,000 394 Antagonist <ref name="pmid18059438" />
5-HT4 Template:Abbr Template:Abbr Template:Abbr Template:Abbr
5-HT5A 3,120 768 Template:Abbr <ref name="pmid18059438" />
5-HT6 1,865 503 Antagonist <ref name="pmid18059438" />
5-HT7 307 76 Antagonist <ref name="pmid18059438" />
α1A 22 144 Antagonist <ref name="pmid18059438" />
α1B 39 95 Antagonist <ref name="pmid18059438" />
α2A 2,230–3,630 237 Antagonist <ref name="pmid18059438" /><ref name="pmid8935801" />
α2B 90–747 378 Antagonist <ref name="pmid18059438" /><ref name="pmid8935801" />
α2C 28.7–350 736 Antagonist <ref name="pmid18059438" /><ref name="pmid8935801" />
β1 >10,000 >10,000 Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
β2 >10,000 >10,000 Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
D1 712 214 Antagonist <ref name="pmid18059438" />
D2 245 196 Antagonist <ref name="pmid18059438" />
D2L 700 Template:Abbr Antagonist <ref name="pmid8935801" />
D2S 390 Template:Abbr Antagonist <ref name="pmid8935801" />
D3 340–483 567 Antagonist <ref name="pmid18059438" /><ref name="pmid8935801" />
D4 1,202 1,297 Antagonist <ref name="pmid18059438" />
D4.2 1,600 Template:Abbr Antagonist <ref name="pmid8935801" />
D5 1,738 1,419 Antagonist <ref name="pmid18059438" />
H1 2.2–11 3.5 Antagonist <ref name="pmid18059438" />
H2 >10,000 298 Antagonist <ref name="pmid18059438" />
H3 >10,000 >10,000 Template:Abbr <ref name="pmid18059438" />
H4 >10,000 1,660 Template:Abbr <ref name="pmid18059438" />
M1 858 39 Antagonist <ref name="pmid18059438" />
M2 1,339 453 Template:Abbr <ref name="pmid18059438" />
M3 >10,000 23 Antagonist <ref name="pmid18059438" />
M4 542 110 Template:Abbr <ref name="pmid18059438" />
M5 1,942 23 Antagonist <ref name="pmid18059438" />
σ1 220–3,651 >10,000 Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
σ2 1,344 1,050 Template:Abbr <ref name="pmid18059438" />
[[NMDA receptor|Template:Abbr
(Template:Abbr)]]		 >10,000 Template:Abbr Antagonist <ref name="pmid18059438" />
Template:Abbrlink >10,000 Template:Abbr Template:Abbr <ref name="pmid18059438" /><ref name="pmid8935801" />
Template:Abbrlink Template:Abbr >10,000
(Template:Abbrlink)		 Template:Abbr <ref name="pmid18059438" />
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except σ1 (guinea pig), σ2 (rat), and Template:Abbr (rat).<ref name="pmid18059438" /><ref name="pmid8935801" />

Quetiapine has the following pharmacological actions:<ref name=Seroquel>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid11132243">Template:Cite journal</ref><ref name="urlNeuropsychopharmacology: the fifth ... - Google Books">Template:Cite book</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="dailymed PI">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Sep 18]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: {{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

This means quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties.<ref>Template:Cite journal</ref> Quetiapine binds strongly to serotonin receptors; the drug acts as a partial agonist at 5-HT1A receptors and as an antagonist to all other serotonin receptors it has affinity for.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref> 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.<ref name="pmid11132243"/><ref>Template:Cite journal</ref> 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.<ref name="low_dose">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

When treating schizophrenia, antagonism of D2 receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5-HT2A receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes.<ref name="Quetiapine"/><ref name="drugbank.ca">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

PharmacokineticsEdit

Peak levels of quetiapine occur 1.5 hours after a dose.<ref name="SeroquelLabel" /> The plasma protein binding of quetiapine is 83%.<ref name="SeroquelLabel" /> The major active metabolite of quetiapine is norquetiapine (N-desalkylquetiapine).<ref name="pmid18059438" /> Quetiapine has an elimination half-life of 6 or 7 hours.<ref name="SeroquelLabel" /><ref name="EMC" /><ref name="DD" /> Its metabolite, norquetiapine, has a half-life of 9 to 12 hours.<ref name="EMC" /><ref name="DD" /> 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.<ref name="drugbank.ca"/><ref name="SeroquelLabel">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

File:Norquetiapine.svg
Skeletal formula of norquetiapine

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ChemistryEdit

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

SynthesisEdit

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.<ref>Warawa, E. J.; Migler, B. M.; 1988, Template:US Patent.</ref>

File:Quetiapine syn.png

HistoryEdit

Sustained-releaseEdit

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.<ref>Template:Cite press release</ref><ref>Template:Cite press release</ref>

In May 2007, the US FDA approved Seroquel XR for acute treatment of schizophrenia.<ref>Template:Cite press release</ref> During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007.<ref>Template:Cite press release</ref> 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.<ref>Template:Cite press release</ref> 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.<ref>Notice of Compliance Information - Seroquel XRTemplate:Dead link 27 September 2007, retrieved 3 December 2007</ref>

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.<ref>Template:Cite press release</ref> 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.<ref>Template:Cite press release</ref>

Society and cultureEdit

Regulatory statusEdit

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.<ref name="Off-label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Quetiapine received its initial approval from the US FDA for the treatment of schizophrenia in 1997.<ref name="dailymed PI" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.<ref>Template:Cite press release</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

LawsuitsEdit

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.<ref name="Off-label"/> 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."<ref name="Off-label"/>

Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, diabetes.<ref>Template:Cite news</ref><ref name="BloombergNewsSeroquelDiabetes">Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite news</ref>

Approximately 10,000<ref>Template:Cite news</ref> lawsuits<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths.

ControversyEdit

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.<ref>Template:Cite news</ref> A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations.<ref>Template:Cite news</ref>

Nurofen Plus tampering caseEdit

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.<ref>Template:Cite press release</ref>

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The contamination was later traced to in-store tampering by a customer.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

ReferencesEdit

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External linksEdit

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