Quetiapine (Seroquel)

Class

Second-generation (atypical) antipsychotic

Mechanism

Antagonist at dopamine D2 and serotonin 5-HT2A receptors; also blocks histamine H1 and alpha-1 adrenergic receptors; active metabolite norquetiapine inhibits norepinephrine reuptake and partially agonizes 5-HT1A receptors

FDA-Approved Use

Schizophrenia, bipolar disorder (manic, mixed, and depressive episodes), adjunctive treatment for major depressive disorder (MDD)

Off-Label Use

Generalized anxiety disorder (GAD), psychosis in Parkinson’s disease (PD), agitation and aggression in dementia, post-stroke affective lability, post-stroke aggression, agitation and aggression in traumatic brain injury (TBI)

Formulation

Oral tablets (immediate- and extended-release)

Titration

25–50 mg p.o. nightly; titrate gradually every few days based on indication and tolerability

Dose Range

50–300 mg/day (for MDD augmentation); up to 800 mg/day for primary psychiatric conditions like schizophrenia or bipolar disorder

Kinetics

Half-life ~6 hours (IR) and ~7 hours (XR); metabolized primarily via CYP3A4; steady state in 1–2 days

Common AEs

Sedation, orthostatic hypotension, weight gain, dry mouth, dizziness, constipation, metabolic changes (e.g., hyperlipidemia, hyperglycemia)

Serious/Rare AEs

Tardive dyskinesia, neuroleptic malignant syndrome (NMS), cataracts, QTc prolongation, leukopenia

Monitoring

Monitor weight, lipids, glucose, blood pressure, and extrapyramidal symptoms (EPS) every 3–6 months; consider periodic ECG in those with cardiac risk

Black Box Warning

Increased risk of mortality in elderly patients with dementia-related psychosis; increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Quetiapine is commonly used off-label to manage agitation and psychosis in dementia, including Alzheimer’s disease (AD) and vascular cognitive impairment, but carries an increased mortality risk in this population. It is often preferred for noncognitive symptoms in dementia with Lewy bodies (DLB) due to lower extrapyramidal side effect risk compared to other antipsychotics, although even low doses (6.25–50 mg/day) require careful monitoring. In Parkinson’s disease (PD), quetiapine is used to manage psychosis but may worsen motor symptoms at higher doses. Caution is warranted in patients with cardiovascular disease or known QTc prolongation, as quetiapine can increase the QT interval. Its sedative properties can be helpful in individuals with comorbid anxiety or insomnia but increase the risk of falls in older adults.