quetiapine quetiapine quetiapine, sold under the brand name seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, borderline personality disorder, and major depressive disorder. despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. it is taken orally. quetiapineclinical datapronunciation/kwɪˈtaɪ.əpiːn/ kwi-ty-ə-peen trade namesseroquel, seroquel xr, temprolide, othersahfs/drugs.commonographmedlineplusa698019license data us dailymed: quetiapine us fda: quetiapine pregnancycategory au: b3 routes ofadministrationby mouthatc coden05ah04 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability100%protein binding83%metabolismliver via cyp3a4-catalysed sulfoxidation to its active metabolite norquetiapine (n-desalkylquetiapine)elimination half-life7 hours (parent compound); 9–12 hours (active metabolite, norquetiapine)excretionkidney (73%), faeces (20%)identifiers iupac name 2-(2-(4-dibenzothiazepine-11-yl-1-piperazinyl)ethoxy)ethanol cas number111974-69-7 ypubchem cid5002iuphar/bps50drugbankdb01224 ychemspider4827 yuniibgl0jsy5sikeggd08456 ychebichebi:8707 ychemblchembl716 ycomptox dashboard (epa)dtxsid9023546 echa infocard100.131.193 chemical and physical dataformulac21h25n3o2smolar mass383.51 g·mol−13d model (jsmol)interactive imagesolubility in water3.29 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 ykey:urkomymaxpyinw-uhfffaoysa-n y (verify) common side effects include sleepiness, constipation, weight gain, 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 serotonin and dopamine. quetiapine was developed in 1985 and approved for medical use in the united states in 1997. it is available as a generic medication. in 2020, it was the 64th most commonly prescribed medication in the united states, with more than 10 million prescriptions. medical uses quetiapine (seroquel) 25 mg tablets, next to us one-cent coin for comparison seroquel xr 150 mg tablet box quetiapine is primarily used to treat schizophrenia or bipolar disorder. quetiapine targets both positive and secondary negative symptoms of schizophrenia. schizophrenia a 2013 cochrane review compared quetiapine to typical antipsychotics: quetiapine compared to typical antipsychotics for schizophrenia 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. outcome findings in words findings in numbers quality of evidence global state no clinical significant responsethere is no clear difference between people given quetiapine and those receiving typical antipsychotic drugs. these findings are based on data of moderate quality.rr 0.96 (0.75 to 1.23)moderate mental state average positive symptom score (panss)on average, people receiving quetiapine scored higher (worse) than people treated with typical antipsychotic drugs. there was, however, no clear difference between the groups. this finding is based on data of moderate quality.md 0.02 higher (0.39 lower to 0.43 higher)*moderate average negative symptom score (panss)on average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. this finding is based on data of moderate quality.md 0.82 lower (1.59 to 0.04 lower)*moderate cognitive function average scoreon average, people receiving quetiapine scored higher (better) than people treated with typical antipsychotic drugs. there was no clear difference between the groups. this finding is based on data of very limited quality.md 1.55 higher (0.62 lower to 3.72 higher)*very low leaving the study early for any reasonquetiapine is not clearly more acceptable than typical antipsychotic drugs. these findings are based on data of moderate quality.rr 0.91 (0.81 to 1.01)moderate adverse effects extrapyramidal effectsquetiapine may reduce the chance of experiencing these movement disorders. this finding is based on data of moderate quality.rr 0.17 (0.09 to 0.32)moderate prolactin levelaverage level (ng/ml)on average, people receiving quetiapine scored lower (better) than people treated with typical antipsychotic drugs. there was a clear difference between the groups. this finding is based on data of moderate quality.md 16.20 lower (23.34 to 9.07 lower)*moderate *the meaning of these findings for day-to-day care is not clear 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. quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended. others 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% ci –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. 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 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. 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-ht2c 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