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quetiapine

Brand: Seroquel, Seroquel XR

⚠ BBW Beers Criteria Prototype: risperidone
Drug Class: antipsychotic
Drug Family: antipsychotic
Subclass: atypical antipsychotic / second-generation
Organ Systems: cns

Mechanism of Action

Low-affinity D2 antagonist (fast dissociation) combined with potent 5-HT2A, H1, and alpha-1/2 blockade; low D2 occupancy minimizes EPS and prolactin elevation; potent H1 antagonism drives sedation and weight gain.

dopamine D2 receptorsserotonin 5-HT2A receptorshistamine H1 receptors

Indications

  • schizophrenia
  • bipolar I mania (acute)
  • bipolar depression (Seroquel XR)
  • major depressive disorder (adjunct)
  • generalized anxiety disorder (off-label)

Contraindications

  • dementia-related psychosis

Adverse Effects

Common

  • sedation (very common, dose-dependent)
  • weight gain
  • dry mouth
  • constipation
  • orthostatic hypotension
  • metabolic syndrome

Serious

  • hyperglycemia / diabetic ketoacidosis
  • tardive dyskinesia (lower risk than typicals)
  • NMS
  • cataracts (long-term use)
  • QTc prolongation

Pharmacokinetics (ADME)

Absorption ~9% bioavailability (extensive first-pass); food increases absorption
Distribution Protein binding 83%; Vd 6–14 L/kg
Metabolism CYP3A4 to multiple active and inactive metabolites
Excretion Renal (~73%); hepatic impairment requires dose reduction
Half-life 7 hours (IR); 12 hours (XR); active metabolite norquetiapine 12 hours
Onset Sedation: hours; antipsychotic: days to weeks
Peak 1–1.5 hours (IR); 5–6 hours (XR)
Duration 12 hours (IR); 24 hours (XR)
Protein Binding 83%
Vd 6–14 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
CYP3A4 inhibitors (ketoconazole, erythromycin) increase quetiapine levels; reduce dose by 1/6 major
CYP3A4 inducers (carbamazepine, phenytoin) reduce quetiapine levels by ~87%; major dose increase required major
CNS depressants additive sedation moderate

Nursing Considerations

  1. Monitor fasting glucose, HbA1c, lipid panel, weight, and BP at baseline and every 3 months; quetiapine carries significant metabolic risk
  2. Slit-lamp eye examinations every 6 months recommended for long-term users due to risk of posterior lens opacities (cataracts)
  3. Sedation is prominent especially at lower doses due to high H1 affinity; quetiapine is frequently misused as a sedative — assess for this at each visit
  4. Counsel patients not to drive or operate machinery until they know how quetiapine affects them; bedtime dosing reduces daytime sedation

Clinical Pearls

  • Quetiapine is one of only two atypical antipsychotics (with lurasidone) FDA-approved for bipolar depression — an important distinction as most antipsychotics only have mania indication
  • At low doses (25–100 mg), quetiapine's H1 and alpha-1 blockade dominate clinical effects (sedation, hypotension) with minimal D2 occupancy — the drug is increasingly used off-label as a sleep aid, raising concerns about off-label prescribing and metabolic risk

Safety Profile

Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Antipsychotic Bipolar Depression (Seroquel XR) Bipolar I Mania (acute) Generalized Anxiety Disorder (off-label) Major Depressive Disorder (adjunct) Schizophrenia
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