Introduction
Quetiapine is an atypical antipsychotic medication approved by the FDA in 1997. It belongs to the dibenzothiazepine class and is widely prescribed for various psychiatric conditions. Marketed under the brand name Seroquel and available as generic formulations, quetiapine has become one of the most commonly prescribed antipsychotic medications worldwide due to its broad therapeutic profile and generally favorable side effect spectrum compared to typical antipsychotics.
Mechanism of Action
Quetiapine exerts its therapeutic effects through antagonism at multiple neurotransmitter receptors. It has high affinity for serotonin 5-HT2A receptors and dopamine D2 receptors, with approximately equal binding affinity for both. Unlike typical antipsychotics, quetiapine demonstrates transient D2 receptor binding and rapid dissociation, which may contribute to its lower incidence of extrapyramidal symptoms.
The drug also acts as an antagonist at histamine H1 receptors (contributing to sedative effects), α1-adrenergic receptors (associated with orthostatic hypotension), and to a lesser extent, α2-adrenergic receptors. Quetiapine has minimal affinity for muscarinic receptors, resulting in relatively low anticholinergic side effects.
Indications
FDA-approved indications:- Schizophrenia (treatment and maintenance)
- Bipolar disorder (acute manic episodes, depressive episodes, and maintenance)
- Major depressive disorder (as adjunctive therapy)
- Generalized anxiety disorder
- Post-traumatic stress disorder
- Insomnia (particularly at low doses)
- Borderline personality disorder
- Treatment-resistant depression
Dosage and Administration
Available formulations:- Immediate-release tablets: 25, 50, 100, 200, 300, 400 mg
- Extended-release tablets: 50, 150, 200, 300, 400 mg
- Schizophrenia: 150-750 mg/day in divided doses (IR) or once daily (XR)
- Bipolar mania: 400-800 mg/day
- Bipolar depression: 300 mg/day
- Adjunct for MDD: 150-300 mg/day
- Hepatic impairment: Reduce initial dose by 50%
- Renal impairment: Use with caution, consider dose reduction
- Elderly: Start with lower doses (25-50 mg/day)
- Pediatrics: Dosing based on weight and indication
- Take with or without food
- XR formulation must be swallowed whole
- Dose titration recommended to minimize side effects
Pharmacokinetics
Absorption: Well-absorbed orally with 100% bioavailability relative to solution. Food has minimal effect on absorption. Peak concentrations reached in 1.5 hours (IR) and 6 hours (XR). Distribution: Volume of distribution approximately 10±4 L/kg. Highly protein bound (83% to serum proteins). Metabolism: Extensively metabolized hepatic via CYP3A4 to inactive and active metabolites (norquetiapine, which has antidepressant properties). Elimination: Half-life approximately 6 hours (IR) and 7 hours (XR). Excreted primarily in urine (73%) and feces (20%). Clearance reduced in elderly patients and those with hepatic impairment.Contraindications
- Hypersensitivity to quetiapine or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors in patients with specific risk factors
- History of serious hypersensitivity reactions to other antipsychotics
Warnings and Precautions
Black Box Warnings:- Increased mortality in elderly patients with dementia-related psychosis
- Suicidal thoughts and behaviors in children, adolescents, and young adults
- Neuroleptic malignant syndrome (NMS)
- Tardive dyskinesia
- Metabolic changes (weight gain, hyperglycemia, dyslipidemia)
- Hyperprolactinemia
- Orthostatic hypotension
- Falls (particularly in elderly)
- Cataracts (routine monitoring recommended)
- QT prolongation (caution in patients with cardiac history)
- Cognitive and motor impairment
Drug Interactions
Major interactions:- Strong CYP3A4 inhibitors (ketoconazole, itraconazole, HIV protease inhibitors): Increase quetiapine levels 5-6 fold
- Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin): Decrease quetiapine levels by 80-90%
- Other CNS depressants (benzodiazepines, opioids, alcohol): Additive sedation
- Antihypertensive agents: Enhanced hypotensive effects
- Drugs that prolong QT interval: Increased risk of arrhythmias
Adverse Effects
Common (≥10%):- Somnolence (dose-related)
- Dry mouth
- Dizziness
- Constipation
- Weight gain
- Dyspepsia
- Orthostatic hypotension
- Tachycardia
- Elevated liver enzymes
- Hyperprolactinemia
- Extrapyramidal symptoms (lower incidence than typical antipsychotics)
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Diabetes mellitus and hyperglycemia
- Leukopenia/neutropenia
- Seizures
- QT prolongation
- Priapism
Monitoring Parameters
Baseline:- Complete medical and psychiatric history
- Weight, height, BMI
- Fasting blood glucose/HbA1c
- Lipid profile
- Liver function tests
- CBC with differential
- ECG (in patients with cardiac risk factors)
- Blood pressure and heart rate
- Eye examination for cataracts
- Weight and BMI at 4, 8, and 12 weeks, then quarterly
- Fasting glucose at 12 weeks, then annually
- Lipid profile at 12 weeks, then every 5 years if normal
- Blood pressure and heart rate regularly
- Assessment for extrapyramidal symptoms and tardive dyskinesia
- Mental status and symptom improvement
- Adherence assessment
Patient Education
- Take medication as prescribed; do not stop abruptly
- XR tablets must be swallowed whole
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting/lying position to prevent dizziness
- Report any unusual movements, fever, muscle stiffness, or changes in mental status
- Regular monitoring of weight, blood sugar, and cholesterol is essential
- Use caution when driving or operating machinery until effects are known
- Notify all healthcare providers of quetiapine use
- Keep medication out of reach of children
- Report pregnancy or plans to become pregnant to healthcare provider
References
1. FDA Prescribing Information: Seroquel (quetiapine). 2023 2. Stahl SM. Stahl's Essential Psychopharmacology. 5th ed. Cambridge University Press; 2021 3. Lehne RA. Pharmacology for Nursing Care. 11th ed. Elsevier; 2022 4. Miller DD. Atypical antipsychotics: sleep, sedation, and efficacy. Prim Care Companion J Clin Psychiatry. 2004;6(2):3-7 5. Komossa K, et al. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010;(1) 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia. 3rd ed. 2021 7. Marder SR, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004;161(8):1334-1349 8. De Hert M, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126
This monograph is for educational purposes only and does not replace professional medical advice. Always consult with a qualified healthcare provider for medication decisions.