Quetiapine
Quetiapine is a second-generation atypical antipsychotic of the dibenzothiazepine class, structurally related to clozapine.12 Developed by AstraZeneca and first approved by the FDA in 1997, it is prescribed for schizophrenia, bipolar disorder, and as an adjunct in major depressive disorder. It is also widely used off-label for insomnia, anxiety, and other conditions. While recreational use is uncommon, reports of misuse have emerged, primarily driven by its sedative and anxiolytic properties.
Contents
Dosage & Duration
Dosage
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
The physical effects of quetiapine can be broken down into several components which progressively intensify proportional to dosage.
Cognitive
The general head space of quetiapine is often described as one of sleepiness, emptiness, apathy, stupor and catatonia. The specific cognitive effects can be broken down into several components which progressively intensify proportional to dosage.
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Quetiapine is a multi-receptor antagonist with its strongest binding affinities at histamine H1 and alpha-1 adrenergic receptors, followed by serotonin 5-HT2A and dopamine D2 receptors.3 It additionally acts as a partial agonist at serotonin 5-HT1A receptors while antagonizing several other serotonin subtypes (5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7), all five dopamine receptor subtypes (D1 through D5), alpha-2 adrenergic receptors, and muscarinic acetylcholine receptors. Its pharmacological profile is dose-dependent: at low doses it functions primarily as an antihistamine and alpha-1 adrenergic blocker, moderate doses incorporate serotonin receptor antagonism, and higher doses recruit dopamine D2 antagonism.4 Relative to its other principal targets, quetiapine has comparatively low D2 affinity, dissociates rapidly from the D2 receptor,5 and achieves only approximately 30% D2 occupancy at therapeutic doses.6
Pharmacokinetics
Quetiapine is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1 to 2 hours.78 Its absolute oral bioavailability is reported as low, and plasma protein binding is approximately 83%.7 Hepatic metabolism proceeds primarily via CYP3A4, with CYP2D6 playing a secondary role, through sulfoxidation and oxidation pathways.78 The principal active metabolite, norquetiapine (N-desalkylquetiapine), reaches roughly one-third the peak concentration of the parent compound and exhibits potent norepinephrine transporter inhibition that may contribute to antidepressant effects.9 The elimination half-life of quetiapine is approximately 6 to 7 hours, while norquetiapine has a longer half-life of 9 to 12 hours. Excretion occurs primarily via the kidneys (73%) and feces (20%), with less than 1% appearing as unchanged drug.7
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Harm Potential
Addiction & Dependence
Psychological
LowLimited abuse potential exists, primarily in individuals with a history of polysubstance abuse or mental illness, and especially in incarcerated settings where access to other intoxicants is restricted.1011 Abuse is driven by sedative and anxiolytic effects rather than antipsychotic properties. Drug-seeking behaviors have been documented, including prisoners threatening legal action or self-harm when faced with discontinuation.10
Physical
ModeratePhysical dependence develops with continued use, and withdrawal symptoms may occur after abrupt cessation following several weeks of steady dosing.12 Gradual tapering is recommended to avoid acute withdrawal syndrome. Withdrawal symptoms include nausea, vomiting, sweating, lightheadedness, insomnia, nervousness, anxiety, tachycardia, and dyskinesia.12
Toxicity
Chronic use is associated with QT interval prolongation and an increased risk of sudden cardiac death, with risk being dose-dependent; low doses under 75 mg daily show minimal increase while higher doses approach risk levels of first-generation antipsychotics.
Asymptomatic elevation of liver enzymes occurs in approximately a quarter of patients after initiating treatment; overt hepatotoxicity is rare.
Extrapyramidal symptoms and tardive dyskinesia can occur but are less common than with first-generation antipsychotics; neuroleptic malignant syndrome is a rare but potentially fatal complication.12
Leukopenia and neutropenia occur in approximately 1% of patients, increasing infection risk; this typically resolves with discontinuation.
Psychosis Risk
As an antipsychotic, quetiapine treats rather than induces psychosis. However, occasional reports of drug-induced mania or hypomania exist. Discontinuation may result in rebound psychosis or recurrence of the underlying condition being treated.19
Seizure Risk
May lower the seizure threshold, though a clinical trial with 3,700 patients did not demonstrate an increased rate of seizures. Seizures are more commonly associated with overdose situations and may occur when combined with other drugs that lower seizure threshold.
History & Culture
Development and Approval
Quetiapine was developed by the pharmaceutical company AstraZeneca during the mid-1980s through the 1990s as part of efforts to improve upon first-generation antipsychotic medications.20 The compound received approval from the U.S. Food and Drug Administration in…
Legality
By Country
References
Source Pages
Citations
- (1998). Quetiapine, an atypical antipsychotic. Clinical Therapeutics. https://pubmed.ncbi.nlm.nih.gov/9855315/1
- (2002). Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing. The Journal of Clinical Psychiatry, 63(Suppl 13), 5–11. https://pubmed.ncbi.nlm.nih.gov/12562141/1
- (November 2000). Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sciences, 68(1), 29–39. https://doi.org/10.1016/s0024-3205(00)00911-51
- Joshi K, Rao S, & Mehta S. (2025). A Review of Pharmacokinetic and Pharmacodynamic Properties of Quetiapine IR and XR: Insights and Clinical Practice Implications. Cureus. https://doi.org/10.7759/cureus.8625812
- (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. https://doi.org/10.1176/appi.ajp.158.3.3601
- (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. https://doi.org/10.1016/s0924-977x(00)00133-41
- DeVane CL, & Nemeroff CB. (2001). Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clinical Pharmacokinetics, 40(7), 509-522. https://pubmed.ncbi.nlm.nih.gov/11510628/123456
- (2021). Variants in COMT, CYP3A5, CYP2B6, and ABCG2 Alter Quetiapine Pharmacokinetics. Frontiers in Pharmacology. https://pmc.ncbi.nlm.nih.gov/articles/PMC8540141/12
- (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. https://doi.org/10.3389/fpsyt.2013.0010212
- (2020). Quetiapine Abuse Fourteen Years Later: Where Are We Now? A Systematic Review. Substance Use & Misuse, 55(2), 304–313. https://doi.org/10.1080/10826084.2019.166801312
- (February 2017). Intentional Recreational Abuse of Quetiapine Compared to Other Second-generation Antipsychotics. The Western Journal of Emergency Medicine, 18(2), 243–250. https://doi.org/10.5811/westjem.2016.10.3232212
- (October 2013). Quetiapine fumarate tablet. DailyMed. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3112a006-1c61-47f2-84f5-9a7670d09c9b1234
- (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. https://doi.org/10.1002/wps.210101
- (November 2016). Evaluation of the use of low-dose quetiapine and the risk of metabolic consequences: A retrospective review. The Mental Health Clinician, 6(6), 308–313. https://doi.org/10.9740/mhc.2016.11.3081
- (January 2023). Impact of low-dose quetiapine-use on glycosylated hemoglobin, triglyceride and cholesterol levels. Acta Psychiatrica Scandinavica, 147(1), 105–116. https://doi.org/10.1111/acps.135151
- (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. https://doi.org/10.1016/s2215-0366(19)30416-x1
- (27 January 2022). Seroquel Xr- quetiapine tablet, extended release. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=473a3ac4-67f4-4782-baa9-7f9bdd8761f4123
- (March 2008). Tardive dyskinesia and new antipsychotics. Current Opinion in Psychiatry, 21(2), 151–156. https://doi.org/10.1097/yco.0b013e3282f531321
- (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. https://doi.org/10.1111/j.1600-0447.2006.00787.x1
- (2013). Quetiapine. New Drug Approvals. https://newdrugapprovals.org/2013/11/11/quetiapine/123
- (n.d.). AstraZeneca losing fight against generic quetiapine. GaBI Online. https://www.gabionline.net/generics/news/AstraZeneca-losing-fight-against-generic-quetiapine1
- (2010). Brown Obtains Multi-Million-Dollar Settlement From Maker of Antipsychotic Drugs. California Department of Justice, Office of the Attorney General. https://oag.ca.gov/news/press-releases/brown-obtains-multi-million-dollar-settlement-maker-antipsychotic-drugs12
- (2010). AstraZeneca 'suppressed' drug test data. BBC News (via PsychRights mirror). https://psychrights.org/2010/100125BBCAstraZenecaSuppressedData.htm1
- (2017). Quetiapine Misuse and Abuse: Is it an Atypical Paradigm of Drug Seeking Behavior?. Journal of Research in Pharmacy Practice, 6(1), 12–15. https://doi.org/10.4103/2279-042x.20098712
- (n.d.). PMS-QUETIAPINE - Product information - Health Canada Drug Product Database. Drug Product Database. https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=781891
- (n.d.). QUETIAPINE ACCORD HEALTHCARE LP 300 mg, comprimé à libération prolongée - Base de Données Publique des Médicaments. Base de Données Publique des Médicaments. https://base-donnees-publique.medicaments.gouv.fr/medicament/62650834/extrait1
- (n.d.). Anlage 1 AMVV - Einzelnorm. https://www.gesetze-im-internet.de/amvv/anlage_1.html1
- (n.d.). SEROQUEL Filmtabl 25 mg - Arzneimittel-Kompendium der Schweiz. Compendium.ch. https://compendium.ch/de/product/81271-seroquel-filmtabl-25-mg1
- (n.d.). Quetiapine 25 mg film-coated tablets - Summary of Product Characteristics (SmPC). electronic Medicines Compendium (eMC). https://www.medicines.org.uk/emc/product/3079/smpc1
Further Reading
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