Generic Name

Seroquel

Drug Class

Atypical antipsychotic

Mechanism

• Dopamine D₂ blockade with a short‑acting interaction, reducing psychotic symptoms while minimizing tardive dyskinesia risk.
• Serotonin 5‑HT₂A antagonism, contributing to mood‑stabilizing and anxiolytic properties.
• Additional antagonism at α₁‑adrenergic, H₁ histamine, and 5‑HT₇ receptors, explaining sedation, orthostatic hypotension, and weight changes.
• The inverse agonist/partial antagonist activity at dopamine D₃ and serotonin 5‑HT₂C influences metabolic effects.

Pharmacokinetics

• Absorption: Oral bioavailability ~85%; peak plasma concentration 1–3 h post‑dose (extended‑release >4 h).
• Distribution: ~90 % plasma protein binding; crosses the blood–brain barrier.
• Metabolism: Primarily via CYP3A4; minor contribution from CYP1A2; metabolites are inactive.
• Half‑life: ~6–7 h (immediate‑release), 20–24 h (extended‑release).
• Excretion: Renally (≈30 %) and hepatically (≈70 % as metabolites); dose adjustment not required for mild–moderate renal impairment.

Indications

• Schizophrenia (acute and maintenance therapy).
• Bipolar I Disorder (mania and mixed states; adjunctive in depressive episodes).
• Adjunctive therapy in treatment‑resistant major depression (off‑label), and for adjustment disorder with anxiety (off‑label).

Contraindications

• Hypersensitivity to quetiapine or other antipsychotics.
• Severe hepatic impairment (CYP3A4 inhibition increases exposure).
• Concomitant QT‑prolonging agents or baseline prolonged QT interval.
• Pregnancy: Category C; use only if benefits outweigh risks.
• Pediatric: Use only in approved indications (e.g., schizophrenia in children ≥12 yr); caution due to weight gain and metabolic effects.
• Elderly: Higher risk of orthostatic hypotension and falls.
• Diabetes mellitus: Monitor glucose; risk of worsening glycemic control.

Dosing

• Titration: Increase by 50 mg every 3–5 days; consider dose‑limiting side effects.
• Steady state: Achieved within 3–5 days due to short half‑life.
• Rapid‑release: Twice daily; XR is once daily after a brief titration phase.

Adverse Effects

Common (≥10 %)
• Sedation / somnolence
• Dizziness / orthostatic hypotension
• Dry mouth
• Weight gain (≈1–3 kg/month)
• Increased appetite
• Metabolic changes (↑ blood glucose, lipids)

Serious (≤1 %)
• QTc prolongation >500 ms
• Extrapyramidal symptoms (rare, <1 %)
• Neuroleptic malignant syndrome (rare)
• Severe metabolic derangements (e.g., hyperglycemia, hyperlipidemia)
• Severe or worsening hypertension (especially with β‑blockers)

Monitoring

• Baseline & periodic: weight, BMI, fasting glucose, HbA1c, lipid panel.
• Cardiac: ECG (baseline & periodic if risk factors), QTc interval monitoring.
• Liver enzymes: AST/ALT at baseline; repeat if AST/ALT >3× ULN.
• Hemogram: CBC with differential if prolonged use or severe sedation.
• Vital signs: Orthostatic BP/HR; assess post‑dose.

Clinical Pearls

• Rapid‑cycling bipolar: XR form can ease daytime dosing; titrate slowly to mitigate sedation.
• Post‑discharge: Initiate at low dose (<25 mg) to reduce risk of orthostatic hypotension in older adults.
• Drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole) increase plasma levels; potent CYP3A4 inducers (e.g., rifampin) reduce efficacy.
• Weight management: Pair with lifestyle counseling; consider adding metformin if risk of diabetes is high.
• Abrupt discontinuation: Avoid sudden withdrawal; taper over 4–6 weeks to prevent rebound mania or psychosis.
• Pregnancy counseling: Discuss potential teratogenicity; use only if no alternative safe antipsychotic exists.
• In patients with liver disease: Consider lower starting dose and monitor serum levels when switching from IR to XR formulations.

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• Quick Reference
• Drug class: Atypical antipsychotic
• Key receptors: D₂, 5‑HT₂A, α₁, H₁
• Half‑life: 6–7 h (IR), 20–24 h (XR)
• Major interactions: CYP3A4 modulators

*For an in‑depth review, consult UpToDate, the FDA label, and the latest American Psychiatric Association guidelines.*