Quetiapine
Seroquel
Second-Generation AntipsychoticGeneric availableTDM data
The mechanism of action of quetiapine in the listed indications is unclear. However, the efficacy of quetiapine in these indications could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5HT 2 ) antagonism. The active metabolite, N-desalkyl quetiapine (norquetiapine), has similar activity at D 2 , but greater activity at 5HT 2A receptors, than the parent drug (quetiapine).
Compare Quetiapine →FDA-Approved Indications
- Schizophrenia (adults; adolescents 13–17 years)
- Acute mania in Bipolar I — mono or adjunct to lithium/divalproex
- Bipolar depression (adults)
- Bipolar I maintenance — adjunct to lithium/divalproex (adults)
- MDD — adjunct to antidepressants (XR, adults)
Common Off-Label Uses
- Insomnia
- Generalized anxiety disorder
- PTSD
- OCD augmentation
- Agitation in dementia
- Delirium
What Sets This Drug Apart
- Dose-dependent receptor profile: low doses (25-100 mg) favor H1/alpha-1 sedation; higher doses (300-800 mg) add meaningful D2 occupancy for psychosis/mania
- Only SGA with FDA approval for bipolar depression (as monotherapy); active metabolite norquetiapine has norepinephrine reuptake inhibition (antidepressant-like property)
- Among the most sedating SGAs in meta-analysis (Nomura 2025 IPD-MA: 23.3% 2-week incidence, highest among 5 drugs tested); tolerance is partial
- Motor side effects minimal: akathisia and parkinsonism essentially at placebo rates; prolactin-neutral — makes it a reasonable option in Parkinson disease psychosis
- Upper-quartile lipid burden (highest LDL ranking in Pillinger NMA) despite mid-class weight gain (~1.9 kg at 6 weeks)
- Lens exam recommended at initiation and every 6 months — cataracts are a quetiapine-specific concern among SGAs
- CYP3A4 substrate; strong 3A4 inhibitors increase exposure ~6-fold
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS