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Quetiapine

Quetiapine molecule structureQuetiapine molecule structure
Seroquel, Seroquel XR, Xeroquel, Ketipinor, Ketilept
Psychoactive Class
Antipsychotic (atypical)
Chemical Class
Dibenzothiazepine derivative

Quetiapine is a second-generation atypical antipsychotic of the dibenzothiazepine class, structurally related to clozapine.citation needed 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.

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~10 mg
Light10-50 mg
Moderate50-150 mg
Strong150-300 mg
Heavy300+ mg
Bioavailability
100% - 100%

Duration

Onset20-40 minutes
Peak1.5-6 hours
Offset6-7 hours
After Effects24-48 hours
Total8-24 hours
Half-life
6-7 hours

Subjective Effects

Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.

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.

SedationDizzinessDehydrationMotor control lossHeadaches

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.

Thought decelerationEmotion suppressionInformation processing suppressionLanguage suppressionAmnesiaAnxiety suppression
Forked from Subjective Effect Documentation byJosie Kins September 2015.

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.citation needed 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. Relative to its other principal targets, quetiapine has comparatively low D2 affinity, dissociates rapidly from the D2 receptor, and achieves only approximately 30% D2 occupancy at therapeutic doses.

Pharmacokinetics

Quetiapine is rapidly absorbed after oral administration, with peak plasma concentrations reached within 1 to 2 hours.12 Its absolute oral bioavailability is reported as low, and plasma protein binding is approximately 83%.citation needed Hepatic metabolism proceeds primarily via CYP3A4, with CYP2D6 playing a secondary role, through sulfoxidation and oxidation pathways. 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. 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.

Interactions

Dangerous

Highest risk

These 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.

DissociativesStimulants

Caution

Use caution

These 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.

1,2-BenzodiazepineAbacavirAbaloparatideAbametapirAbatacept
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Tolerance

Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.

Full Tolerance
Tolerance develops to the antipsychotic effects within approximately one week of continuous use. The most noticeable tolerance develops to the sedative properties of the drug. Some evidence suggests tolerance to sleep-promoting effects may build quickly, though limited research indicates benefits for insomnia may persist for at least 6 weeks in some individuals.
Baseline Reset
Tolerance returns to baseline within 7 to 14 days after cessation of use.

Harm Potential

Addiction & Dependence

Psychological

Low

Limited 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.citation needed 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.

Physical

Moderate

Physical dependence develops with continued use, and withdrawal symptoms may occur after abrupt cessation following several weeks of steady dosing.citation needed Gradual tapering is recommended to avoid acute withdrawal syndrome. Withdrawal symptoms include nausea, vomiting, sweating, lightheadedness, insomnia, nervousness, anxiety, tachycardia, and dyskinesia.

Toxicity

Cardiovascular

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.

Metabolic/Endocrine

Long-term use is associated with weight gain averaging 1-3 kg over several months, along with hyperglycemia, elevated triglycerides, and increased diabetes risk; these metabolic effects may occur even at low doses used for insomnia.citation needed

Hepatic

Asymptomatic elevation of liver enzymes occurs in approximately a quarter of patients after initiating treatment; overt hepatotoxicity is rare.

Neurological

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.citation needed

Hematological

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.citation needed

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.citation needed The compound received approval from the U.S. Food and Drug Administration in September 1997 and

Legality

International

Quetiapine does not appear in the INCB lists of narcotic drugs controlled by the 1961 Convention or psychotropic substances controlled by the 1971 Convention, nor in the precursor Tables I and II for the 1988 Convention.

By Country

Controlled / restricted2
Brazil flagBrazilRestricted
South Africa flagSouth AfricaRestricted
Prescription21
United States flagUnited StatesPrescription only
Australia flagAustraliaPrescription only
Austria flagAustriaPrescription only
Belgium flagBelgiumPrescription only
Canada flagCanadaPrescription only
Colombia flagColombiaPrescription only
France flagFrancePrescription only
Germany flagGermanyPrescription only
Ireland flagIrelandPrescription only
Israel flagIsraelPrescription only
Japan flagJapanPrescription only
Netherlands flagNetherlandsPrescription only
New Zealand flagNew ZealandPrescription only
Norway flagNorwayPrescription only
Philippines flagPhilippinesPrescription only
Poland flagPolandPrescription only
Spain flagSpainPrescription only
Sweden flagSwedenPrescription only
Switzerland flagSwitzerlandPrescription only
Thailand flagThailandPrescription only
United Kingdom flagUnited KingdomPrescription only

References

Source Pages

  1. DrugBank
  2. DrugBank: Quetiapine Biointeractions
  3. DrugBank: Quetiapine Clinical Use
  4. DrugBank: Quetiapine Efficacy
  5. DrugBank: Quetiapine Pharmacology
  6. DrugBank: Quetiapine Quality of Life
  7. DrugBank: Quetiapine Salts
  8. Erowid
  9. Isomer Design (TiHKAL/PiHKAL)
  10. PsychonautWiki
  11. The Drug Classroom
  12. TripSit Factsheets
  13. Wikipedia

Citations

  1. DeVane CL, & Nemeroff CB. (2001). Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clinical Pharmacokinetics, 40(7), 509-522. https://pubmed.ncbi.nlm.nih.gov/11510628/123
  2. Variants in COMT, CYP3A5, CYP2B6, and ABCG2 Alter Quetiapine Pharmacokinetics. Frontiers in Pharmacology (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8540141/1
  3. Christoph U Correll, & Eva M Schenk. (March 2008). Tardive dyskinesia and new antipsychotics. Current Opinion in Psychiatry, 21(2), 151–156. https://doi.org/10.1097/yco.0b013e3282f531321
  4. Quetiapine. New Drug Approvals (2013). https://newdrugapprovals.org/2013/11/11/quetiapine/1
  5. AstraZeneca losing fight against generic quetiapine. GaBI Online (n.d.). https://www.gabionline.net/generics/news/AstraZeneca-losing-fight-against-generic-quetiapine1
  6. Brown Obtains Multi-Million-Dollar Settlement From Maker of Antipsychotic Drugs. California Department of Justice, Office of the Attorney General (2010). https://oag.ca.gov/news/press-releases/brown-obtains-multi-million-dollar-settlement-maker-antipsychotic-drugs1
  7. Therapeutic Goods (Poisons Standard) 2026. legislation.gov.au (n.d.). https://www.legislation.gov.au/F2026L00060/asmade/2026-01-30/text/original/pdf1
  8. Arzneispezialitätenregister (Quetiapin 1A Pharma 25 mg Fachinformation). aspregister.basg.gv.at (n.d.). https://aspregister.basg.gv.at/document/servlet?action=show&type=DOTC_FACH_INFO&zulnr=1-287191
  9. Arzneispezialitätenregister (Quetiapin 1A Pharma 25 mg Fachinformation). basg.gv.at (n.d.). https://www.basg.gv.at/konsumentinnen/wissenswertes-ueber-arzneimittel/rezeptpflicht1
  10. FAGG medicine product information. app.fagg-afmps.be (n.d.). https://app.fagg-afmps.be/pharma-status/api/files/62bc54a11e5c015ab3b5f6e51

Further Reading

  1. Gefvert et al. 2001 - D2 and 5HT2A receptor occupancy PET study
  2. Kapur et al. 2000 - Rapid D2 dissociation PET study
  3. Nord et al. 2013 - Norepinephrine transporter occupancy
  4. PMC: Quetiapine Misuse and Abuse
  5. Psychopharmacology Institute: Mechanism of Action
  6. StatPearls: Quetiapine

Article Status

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    An autonomous workflow built by Josie Kins compiled this article's foundation from information published across the web.

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    No one has reviewed this article's citations yet. That second pass checks each claim against the source it cites.

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  1. Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more

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