Quetiapine

Generic Name

Quetiapine fumarate

Brand Names

Seroquel

Seroquel XR (extended-release)

Qutan

Ketipinor

Xetirest

Others depending on regional markets

Drug Class

Second-generation (atypical) antipsychotic

Dibenzothiazepine derivative

Psychotropic agent

Mechanism of Action

Quetiapine exhibits its antipsychotic effects by antagonizing multiple neurotransmitter receptors in the brain

It primarily blocks serotonin (5-HT2A) and dopamine (D2) receptors, contributing to antipsychotic efficacy and reduced extrapyramidal symptoms (EPS) compared to typical antipsychotics

Also antagonizes histamine H1, adrenergic α1 and α2 receptors, and has moderate affinity for muscarinic receptors

At low doses, its effects are primarily antihistaminergic and sedative

At moderate doses, 5-HT2A antagonism predominates (antidepressant and anxiolytic effects)

At high doses, D2 antagonism contributes significantly (antipsychotic effect)

Indications

Approved Indications

Schizophrenia in adults and adolescents (13–17 years)

Bipolar disorder

• Bipolar I mania (acute and maintenance)

• Bipolar depression

• Bipolar maintenance (as monotherapy or adjunct)
  Major depressive disorder (MDD) adjunct treatment (extended-release only)

Off-Label Uses

Generalized anxiety disorder (GAD)

Post-traumatic stress disorder (PTSD)

Insomnia (especially low-dose use)

Delirium (hospital setting)

Borderline personality disorder

Parkinson’s disease psychosis (with caution)

Agitation in dementia (use discouraged due to mortality risk)

Dosage and Administration

Schizophrenia (IR formulation)

Start: 25 mg twice daily

Increase daily by 25–50 mg to target 300–400 mg/day by Day 4

Usual dose: 150–750 mg/day in divided doses

Max: 800 mg/day

Schizophrenia (XR formulation)

Start: 300 mg once daily

Titrate to 400–800 mg once daily

Initial dose titration required to reduce sedation and hypotension risk

Bipolar Mania (as monotherapy or adjunct to lithium/valproate)

IR: Start 50 mg twice daily

Increase to 400–800 mg/day

XR: Start 300 mg once daily, increase to 400–600 mg

Bipolar Depression

IR: Start 50 mg at bedtime, increase to 300 mg on Day 4

XR: Start 50 mg/day, titrate to 300 mg/day

Optimal dose: 300 mg once daily at bedtime

Major Depressive Disorder (Adjunct)

XR only

Start: 50 mg/day

Titrate to 150–300 mg/day

Geriatric Dosing

Start at low doses (12.5–25 mg), titrate cautiously

Increased risk of orthostatic hypotension, sedation, and falls

Hepatic Impairment

Reduce initial dose to 25 mg/day

Titrate slowly with close monitoring

Renal Impairment

No dosage adjustment necessary

Use with caution in severe renal dysfunction

Pediatric Use

Approved for schizophrenia and bipolar mania in adolescents

Not approved for bipolar depression or MDD in children

Pharmacokinetics

Absorption

Well absorbed orally

Bioavailability ~100%

Peak plasma concentration in 1.5 hours (IR), 5 hours (XR)

Distribution

Highly protein-bound (~83%)

Widely distributed throughout the body

Metabolism

Extensively metabolized in the liver via CYP3A4

Major active metabolite: norquetiapine (also contributes to clinical effects)

Elimination

Excreted mostly in urine (~73%) and feces (~20%) as metabolites

Half-life: 6 hours (IR), 7 hours (XR)

Clearance reduced in hepatic impairment

Contraindications

Known hypersensitivity to quetiapine or its ingredients

Concomitant use with strong CYP3A4 inhibitors (for XR formulation without proper dose adjustment)

Concomitant use with QT-prolonging drugs in high-risk patients

Black Box Warnings

Increased mortality in elderly patients with dementia-related psychosis

Suicidality in children, adolescents, and young adults (similar to other antidepressants)

Warnings and Precautions

Metabolic Effects

Weight gain, hyperglycemia, and dyslipidemia

Monitor BMI, fasting glucose, and lipids regularly

Neuroleptic Malignant Syndrome (NMS)

Rare but potentially fatal

Signs include hyperthermia, altered mental status, muscle rigidity

Requires immediate discontinuation

Tardive Dyskinesia (TD)

Involuntary, repetitive movements (especially orofacial)

More common with long-term use and elderly patients

May be irreversible

Orthostatic Hypotension

Due to α1-adrenergic antagonism

Common in early treatment phase

Slow dose titration recommended

Leukopenia, Neutropenia, Agranulocytosis

Rare but serious

Monitor complete blood counts if unexplained infections or fever

Cataracts

Quetiapine associated with lens changes in animal studies

Periodic ophthalmic exams recommended for long-term users

QT Prolongation

Dose-dependent risk

Caution in patients with known cardiac disease, electrolyte disturbances, or on QT-prolonging agents

Sleep Attacks and Sedation

High sedative potential due to H1 antagonism

Warn patients about driving or operating machinery

Impulse Control Disorders

Including pathological gambling, hypersexuality, compulsive spending

Assess behavior changes regularly

Withdrawal Syndrome

Abrupt discontinuation can cause nausea, insomnia, headache, and irritability

Taper gradually over ≥1 week if possible

Adverse Effects

Very Common

Drowsiness

Dizziness

Dry mouth

Weight gain

Increased appetite

Common

Orthostatic hypotension

Constipation

Fatigue

Dyspepsia

Elevated triglycerides or cholesterol

Irritability

Restlessness (akathisia)

Uncommon

Seizures

Liver enzyme elevations

Leukopenia

Sinus tachycardia

ECG changes

Rare and Serious

Neuroleptic malignant syndrome

Tardive dyskinesia

Suicidal ideation

Agranulocytosis

Pancreatitis

Priapism

Severe hyperglycemia or ketoacidosis

Myocarditis

Angle-closure glaucoma

Overdose

Symptoms

Somnolence

Tachycardia

Hypotension

Seizures

QT prolongation

Rarely fatal unless combined with other CNS depressants

Management

Supportive and symptomatic care

Monitor ECG and vitals

Activated charcoal within 1 hour may help

No specific antidote

Drug Interactions

CYP3A4 Inhibitors (ketoconazole, erythromycin, ritonavir)

Increased plasma levels of quetiapine

Reduce quetiapine dose or avoid combination

CYP3A4 Inducers (carbamazepine, phenytoin, rifampin)

Reduce quetiapine levels significantly

May require dose increase or alternative agent

QT-Prolonging Drugs (amiodarone, macrolides, fluoroquinolones)

Additive risk

Avoid or monitor with ECG

Antihypertensives and CNS Depressants

Additive hypotension or sedation

Monitor closely

Levodopa and Dopaminergic Agents

Quetiapine may antagonize effects

Avoid unless necessary

Alcohol

Increases CNS depression

Avoid concomitant use

Use in Special Populations

Pregnancy

Category C (older FDA classification)

Limited human data

Use only if benefits outweigh risks

Monitor neonates for withdrawal or extrapyramidal symptoms if used in late pregnancy

Lactation

Excreted in breast milk

Breastfeeding not recommended during use

Pediatrics

Approved for use in schizophrenia (13–17) and bipolar mania (10–17)

Monitor growth, weight, glucose, and mood

Geriatrics

Use with caution due to increased risk of sedation, falls, and metabolic effects

Avoid for behavioral disturbances in dementia

Monitoring Parameters

Weight, BMI: baseline, monthly for first 3 months, then quarterly

Fasting blood glucose and lipid panel: baseline, at 3 months, then annually

Blood pressure: baseline and periodically

CBC: baseline and periodically if risk of hematologic toxicity

Liver function tests: baseline and periodically

Mental health assessment: suicidal ideation, mood symptoms, psychosis

ECG if cardiac risk factors or concurrent QT-prolonging agents

Ophthalmologic exams periodically with long-term use

Comparative Pharmacology

Quetiapine vs Olanzapine

Quetiapine less weight gain and metabolic risk

Olanzapine more potent antipsychotic but higher risk for diabetes

Quetiapine vs Risperidone

Risperidone more EPS and prolactin elevation

Quetiapine better tolerated in terms of motor side effects

Quetiapine vs Aripiprazole

Aripiprazole is partial agonist (lower sedation and weight gain)

Quetiapine more sedating and used more for depressive symptoms

Quetiapine vs Clozapine

Clozapine superior for refractory schizophrenia

Quetiapine preferred for better safety profile

Formulations Available

Immediate-release tablets: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg

Extended-release tablets (Seroquel XR): 50 mg, 150 mg, 200 mg, 300 mg, 400 mg

All formulations are oral

No injectable formulation available

Regulatory and Legal Status

Prescription-only medicine

Approved globally for schizophrenia, bipolar disorder, and MDD adjunct

Included in clinical guidelines for mood and psychotic disorders