Quetiapine (Seroquel): Uses, Dosage, Side Effects, and What to Expect

Quetiapine (brand name: Seroquel / Seroquel XR) is a atypical antipsychotic (second-generation). Quetiapine has a complex pharmacological profile. It antagonizes dopamine D2 receptors (loosely, allowing fast dissociation), serotonin 5-HT2A receptors, histamine H1 receptors, and alpha-1 adrenergic receptors. Its active metabolite norquetiapine is a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, which likely contributes to its antidepressant effects. The dose-dependent pharmacology means different doses target different conditions.

• Schizophrenia
• Bipolar I Disorder (manic and depressive episodes)
• Bipolar II Depression
• Major Depressive Disorder (adjunctive with antidepressant)

Common off-label uses:

• Insomnia (widely prescribed at low doses, though not FDA-approved)
• Generalized Anxiety Disorder
• PTSD
• Delirium
• Agitation in dementia

Varies significantly by indication. Schizophrenia: 150-750 mg/day. Bipolar mania: 400-800 mg/day. Bipolar depression: 300 mg/day (target dose). Adjunctive MDD: 150-300 mg/day. Off-label insomnia: 25-100 mg (common but not evidence-based for this use). XR formulation is dosed once daily; IR is typically twice daily.

Sedative effects are immediate. Antipsychotic effects take 1-2 weeks. Antidepressant effects in bipolar depression typically take 1-2 weeks (faster than standard antidepressants).

• Sedation and somnolence (especially at initiation)
• Weight gain (significant — average 2-5 kg in clinical trials)
• Dry mouth
• Dizziness and orthostatic hypotension
• Increased appetite
• Constipation
• Elevated triglycerides and cholesterol

• Metabolic syndrome (weight gain, diabetes, dyslipidemia — monitor regularly)
• Tardive dyskinesia (lower risk than typical antipsychotics but possible)
• Neuroleptic malignant syndrome (rare)
• QT prolongation
• Cataracts (monitor with lens exam)
• Increased mortality in elderly with dementia (FDA black box warning)

CYP3A4 substrate — levels increased by ketoconazole, erythromycin, and similar inhibitors. Levels decreased by CYP3A4 inducers (carbamazepine, phenytoin, rifampin). Avoid alcohol due to additive sedation.

FDA Pregnancy Category C. Atypical antipsychotics may increase risk of gestational diabetes and excessive neonatal sedation. Third-trimester use may cause extrapyramidal symptoms in newborns.

Taper gradually to avoid rebound insomnia, nausea, and potential psychosis relapse. Discontinuation symptoms can include insomnia, anxiety, and withdrawal psychosis in schizophrenia.