Quetiapine: Difference between revisions

| halflife          = ~6 h (parent compound, immediate-release); ~9-12 h (active metabolite N-desalkylquetiapine, also called norquetiapine)

| bioavailability  = Tablet ~100% relative to oral solution; extensive first-pass metabolism

| mechanism        = Dopamine D2 and serotonin 5-HT2A receptor antagonist<ref name="quet-mech">S1</ref> <vote slug="atypical-claim-quet">Quetiapine acts as an antagonist at dopamine D2 and serotonin 5-HT2A receptors and has substantial activity at histaminergic, adrenergic, and other receptors that contribute to its clinical effects.</vote>

| intro            = Quetiapine, marketed as Seroquel, is the most widely prescribed neuroleptic medicine in the United States, accounting for approximately 28% of neuroleptic prescriptions.<ref name="dhc2025">Definitive Healthcare. Antipsychotic Prescription Trends, December 2024-November 2025. Prescription data aggregator.</ref> It is a dibenzothiazepine atypical neuroleptic developed in 1985 at the pharmaceutical division of [[Imperial Chemical Industries]] in Macclesfield, United Kingdom (later [[Zeneca]], then [[AstraZeneca]]), and approved by the United States [[Food and Drug Administration]] on 26 September 1997 for the treatment of [[Schizophrenia|schizophrenia]]. Subsequent FDA approvals expanded the labeled indications to include acute [[Bipolar disorder|bipolar mania]] (2004), bipolar depression (2006), bipolar maintenance (2008), and adjunctive treatment of [[Major depressive disorder|major depressive disorder]] (2009). Quetiapine is widely prescribed at low doses (25-150 mg) off-label for [[Insomnia|insomnia]], anxiety, agitation, [[Post-traumatic stress disorder|post-traumatic stress disorder]], and behavioral disturbances of [[Dementia|dementia]]; this off-label use accounts for the dominant share of quetiapine prescribing in the United States and most other markets. The off-label prescribing pattern was the subject of the largest civil settlement for off-label marketing in pharmaceutical history at the time, when AstraZeneca paid $520 million to the United States [[Department of Justice]] in 2010 to resolve allegations that the company had illegally marketed Seroquel for indications never approved by the FDA.

| pregnancy_details = Quetiapine crosses the placenta in modest amounts (umbilical cord-to-maternal plasma ratio approximately 24%, lower than risperidone or olanzapine).<ref name="newport2007">Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S, Knight BT, Gibson BB, Viguera AC, Owens MJ, Nemeroff CB, Stowe ZN. Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes. American Journal of Psychiatry. 2007;164(8):1214-1220. PMID: 17671284.</ref> The pregnancy literature on atypical neuroleptics has substantially attenuated earlier concerns about teratogenicity; recent large cohort analyses using active-comparator designs and confounding-by-indication adjustment have found no consistent signal for major congenital malformations with quetiapine specifically.<ref name="huybrechts2016">Huybrechts KF, Hernandez-Diaz S, Patorno E, Desai RJ, Mogun H, Dejene SZ, Cohen JM, Panchaud A, Cohen L, Bateman BT. Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry. 2016;73(9):938-946. PMID: 27540849.</ref> Quetiapine is therefore frequently used in pregnancy when neuroleptic treatment is clinically necessary, both for primary indications such as bipolar disorder and schizophrenia and as a substitute for higher-risk medicines such as [[Valproic acid|valproate]].

For women with bipolar disorder or schizophrenia maintained on quetiapine who become pregnant, continuation is generally preferred to discontinuation because of relapse risk; the medicine's relative safety profile in pregnancy makes the maternal mental health argument straightforward. For women on quetiapine off-label for sleep or anxiety, pregnancy is an appropriate occasion to deprescribe in favor of behavioral interventions or, where pharmacotherapy is required, evidence-based alternatives such as the SSRI [[Sertraline|sertraline]].

Management is primarily supportive: airway protection, intravenous fluids for hypotension, ECG monitoring with attention to QT and arrhythmias, cardiac monitoring for at least 24 hours in significant ingestions. [[Activated charcoal|Activated charcoal]] may be considered within one hour of ingestion if the airway is protected. [[:Category:Vasopressors|Vasopressors]] ([[Norepinephrine (medication)|norepinephrine]] preferred over [[Dopamine (medication)|dopamine]], given quetiapine's alpha-1 antagonism) for refractory hypotension. There is no specific antidote. [[Hemodialysis|Hemodialysis]] is not effective owing to the large volume of distribution.

| counseling        = '''Off-label use: most quetiapine prescriptions are for indications the medicine is not formally approved to treat.''' If quetiapine has been prescribed for sleep, anxiety, agitation, or PTSD, the patient should understand that the prescribing is off-label, that the evidence base for these indications is modest, that the metabolic and cardiovascular risk profile applies even at low doses, and that evidence-based alternatives exist ([[Cognitive behavioral therapy for insomnia|cognitive behavioral therapy for insomnia]], SSRIs and SNRIs for anxiety, exposure-based therapies for PTSD).

[[Category:Neuroleptics]]

[[Category:Second-generation neuroleptics]]

[[Category:Medicines]]