Seroquel - Drug Monograph

Introduction

Seroquel (quetiapine) is an atypical antipsychotic medication approved by the FDA in 1997. It belongs to the dibenzothiazepine class and is widely used in psychiatric practice for its efficacy in treating various mental health conditions. Quetiapine functions as a multi-receptor targeting agent with particular affinity for serotonin and dopamine receptors, distinguishing it from conventional antipsychotics.

Mechanism of Action

Quetiapine exerts its therapeutic effects through antagonism at multiple neurotransmitter receptors. It demonstrates high affinity for serotonin 5-HT2A receptors and moderate affinity for dopamine D2 receptors. The drug also acts as an antagonist at histamine H1, adrenergic α1, and α2 receptors. Unlike first-generation antipsychotics, quetiapine's transient D2 receptor binding and greater 5-HT2A than D2 affinity contribute to its reduced risk of extrapyramidal symptoms. Its metabolite, norquetiapine, additionally functions as a norepinephrine reuptake inhibitor, contributing to the drug's antidepressant and anxiolytic properties.

Indications

FDA-approved indications:

• Schizophrenia (acute and maintenance treatment)
• Bipolar disorder (acute manic episodes, depressive episodes, and maintenance therapy)
• Major depressive disorder (as adjunctive therapy)

Off-label uses (with varying evidence support):

• Generalized anxiety disorder
• Insomnia
• Post-traumatic stress disorder
• Borderline personality disorder

Dosage and Administration

• Initial: 25 mg twice daily, titrate to 300-400 mg daily by day 4
• Maintenance: 150-750 mg daily in divided doses

• Initial: 50 mg twice daily, titrate to 400-800 mg daily by day 4
• Maintenance: 400-800 mg daily

• Initial: 50 mg at bedtime, titrate to 300 mg daily by day 4

• Initial: 50 mg at bedtime, titrate to 150-300 mg daily

• Hepatic impairment: Reduce dose by approximately 25%
• Renal impairment: Use with caution; initial dose reduction recommended
• Elderly: Initiate at lower doses (25-50 mg daily) due to increased sensitivity
• Pediatrics: Dosing based on weight and indication (FDA-approved for schizophrenia ≥13 years, bipolar mania ≥10 years)

Pharmacokinetics

• Absorption: Well absorbed orally with 73% bioavailability; high-fat meals increase absorption by 15-20%
• Distribution: Volume of distribution: 10±4 L/kg; 83% protein bound
• Metabolism: Extensive hepatic metabolism primarily via CYP3A4; forms active metabolite norquetiapine
• Elimination: Half-life: approximately 6 hours; excreted primarily in urine (73%) and feces (20%)

Contraindications

• Hypersensitivity to quetiapine or any component of the formulation
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, HIV protease inhibitors)
• Patients with known history of neuroleptic malignant syndrome
• Use in patients with dementia-related psychosis (increased mortality risk)

Warnings and Precautions

• Increased mortality in elderly patients with dementia-related psychosis
• Suicidal thoughts and behaviors in children, adolescents, and young adults

• Metabolic changes: Hyperglycemia, dyslipidemia, weight gain
• Orthostatic hypotension
• Cataracts and lens changes (require periodic eye examinations)
• Leukopenia/neutropenia
• QT prolongation (monitor in patients with cardiac risk factors)
• Hyperthermia and heat-related illness
• Cognitive and motor impairment
• Dysphagia and aspiration risk
• Withdrawal symptoms upon discontinuation

Drug Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): Increase quetiapine levels
• CYP3A4 inducers (e.g., carbamazepine, phenytoin): Decrease quetiapine levels
• Antihypertensive agents: Enhanced hypotensive effects
• CNS depressants: Additive sedation
• Drugs that prolong QT interval: Increased risk of cardiac arrhythmias

Adverse Effects

• Somnolence (18-54%)
• Dry mouth (9-44%)
• Dizziness (10-18%)
• Constipation (8-11%)
• Weight gain (5-23%)
• Dyspepsia (5-10%)

• Neuroleptic malignant syndrome
• Tardive dyskinesia
• Seizures
• Diabetes mellitus and hyperglycemia
• Orthostatic hypotension and syncope
• Suicidal ideation
• Priapism
• Blood dyscrasias

Monitoring Parameters

• Complete metabolic panel (including glucose and lipids)
• Weight and BMI
• Blood pressure and heart rate (sitting and standing)
• ECG in patients with cardiac risk factors
• Eye examination
• Assessment of extrapyramidal symptoms

• Weight and BMI every 3 months
• Glucose and lipids at 3 months and annually
• Blood pressure regularly
• Periodic assessment for TD (using AIMS scale)
• Therapeutic response and side effect assessment
• Adherence evaluation

Patient Education

• Take medication as prescribed; do not abruptly discontinue
• Avoid alcohol and other CNS depressants
• Rise slowly from sitting/lying position to prevent dizziness
• Report any unusual movements, fever, muscle rigidity, or confusion
• Monitor for signs of hyperglycemia (increased thirst, urination, hunger)
• Use caution when driving or operating machinery until effects are known
• Inform all healthcare providers about quetiapine use
• Notify physician if pregnant, planning pregnancy, or breastfeeding
• Keep medication in secure location away from others

References

1. FDA Prescribing Information: Quetiapine (Seroquel). 2023 2. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2004;161(2 Suppl):1-56. 3. McIntyre RS, Soczynska JK, Woldeyohannes HO, et al. A randomized, double-blind, controlled trial evaluating the effect of quetiapine extended-release on depressive symptoms in patients with bipolar depression. J Clin Psychiatry. 2013;74(3):e223-e230. 4. DeVane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine: an atypical antipsychotic. Clin Pharmacokinet. 2001;40(7):509-522. 5. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. 6. Kane JM, Correll CU. Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry. 2010;71(9):1115-1124.