Quetiapine

# Quetiapine ## Overview - **Classification**: Atypical Antipsychotic (Second Generation Antipsychotic) - **Mechanism**: Antagonizes multiple neurotransmitter receptors, including serotonin (5-HT2) and dopamine (D2) receptors. Also has affinity for histamine H1 and adrenergic alpha1/alpha2 receptors. ## Primary Indications 1. **Schizophrenia** - Treatment of acute and maintenance phases. 2. **Bipolar I Mania** - Monotherapy or adjunct to lithium/divalproex. 3. **Bipolar Depression** - Monotherapy. 4. **Major Depressive Disorder (MDD)** - Adjunctive treatment to antidepressants. ## Adult Dosing ### Standard Dosing **Schizophrenia (Quetiapine IR)** - **Initiation Dose**: **25 mg** BID on Day 1. - **Titration**: Increase to **50-75 mg** BID-TID by Day 4. - **Maintenance Dose**: **150-750 mg/day** in 2-3 divided doses. - **Route**: Oral. - **Maximum Dose**: **750 mg/day**. **Schizophrenia (Quetiapine XR)** - **Initiation Dose**: **300 mg** once daily (Day 1). - **Titration**: Can increase by **300 mg/day** on Day 2 to **600 mg** once daily. - **Maintenance Dose**: **400-800 mg** once daily. - **Route**: Oral, take without food or with a light meal. - **Maximum Dose**: **800 mg/day**. **Bipolar I Mania (Monotherapy/Adjunct - Quetiapine IR)** - **Initiation Dose**: **50 mg** BID on Day 1, then **100 mg** BID on Day 2. - **Titration**: Increase to **200 mg** BID by Day 4. - **Maintenance Dose**: **400-800 mg/day** in 2 divided doses. - **Route**: Oral. - **Maximum Dose**: **800 mg/day**. **Bipolar I Mania (Quetiapine XR)** - **Initiation Dose**: **300 mg** once daily on Day 1, then **600 mg** once daily on Day 2. - **Maintenance Dose**: **400-800 mg** once daily. - **Route**: Oral, take without food or with a light meal. - **Maximum Dose**: **800 mg/day**. **Bipolar Depression (Quetiapine IR)** - **Initiation Dose**: **50 mg** once daily at bedtime on Day 1. - **Titration**: **100 mg** once daily on Day 2, then **200 mg** once daily on Day 3. - **Maintenance Dose**: **300 mg** once daily. - **Route**: Oral. - **Maximum Dose**: **300 mg/day**. **Bipolar Depression (Quetiapine XR)** - **Initiation Dose**: **50 mg** once daily at bedtime on Day 1. - **Titration**: **100 mg** once daily on Day 2, then **200 mg** once daily on Day 3. - **Maintenance Dose**: **300 mg** once daily. - **Route**: Oral, take without food or with a light meal. - **Maximum Dose**: **300 mg/day**. **Adjunctive MDD (Quetiapine XR only)** - **Initiation Dose**: **50 mg** once daily at bedtime on Day 1. - **Titration**: May increase to **150 mg** once daily on Day 3 based on response/tolerability. - **Maintenance Dose**: **150-300 mg** once daily. - **Route**: Oral, take without food or with a light meal. - **Maximum Dose**: **300 mg/day**. ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment recommended by manufacturer. - **Hepatic Impairment**: Initial dose **25 mg/day** (IR) or **50 mg/day** (XR). Titrate slowly. - **Elderly Patients (>65 years)**: Initial dose **25 mg/day** (IR) or **50 mg/day** (XR). Titrate slower and to lower target doses. ## Pediatric Dosing ### Neonates (0-28 days) - **Not recommended**: Safety and efficacy not established. ### Infants (1-12 months) - **Not recommended**: Safety and efficacy not established. ### Children (1-10 years) - **Not recommended**: Safety and efficacy not established. ### Children (10-17 years) **Schizophrenia (Quetiapine IR)** - **Indication**: Schizophrenia. - **Initiation Dose**: **25 mg** BID on Day 1. - **Titration**: Increase to **50 mg** BID on Day 2, then **100 mg** BID on Day 3, then **150 mg** BID on Day 4, then **200 mg** BID on Day 5. - **Target Dose**: **400 mg/day** in 2 divided doses. - **Route**: Oral. - **Maximum Dose**: **800 mg/day**. - **Special Notes**: Monitor for suicidal thoughts/behaviors, EPS, weight gain, metabolic changes. **Bipolar Mania (Quetiapine IR)** - **Indication**: Bipolar Mania. - **Initiation Dose**: **25 mg** BID on Day 1. - **Titration**: Increase to **50 mg** BID on Day 2, then **100 mg** BID on Day 3, then **150 mg** BID on Day 4, then **200 mg** BID on Day 5. - **Target Dose**: **400-600 mg/day** in 2 divided doses. - **Route**: Oral. - **Maximum Dose**: **800 mg/day**. - **Special Notes**: Monitor for suicidal thoughts/behaviors, EPS, weight gain, metabolic changes. ### Adolescents (13-18 years) - **Dose**: Follow dosing for Children (10-17 years) for approved indications (Schizophrenia, Bipolar Mania). - **Maximum**: **800 mg/day**. - **Special Notes**: Consider growth and pubertal development. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to quetiapine. - **Relative**: Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, indinavir, nefazodone). ### Common Adverse Effects - **Very Common (>10%)**: Somnolence, dry mouth, dizziness, weight gain, increased triglycerides, increased total cholesterol. - **Common (1-10%)**: Orthostatic hypotension, tachycardia, constipation, dyspepsia, asthenia, blurred vision, EPS (low risk), elevated liver enzymes, increased blood glucose. - **Serious but Rare**: Neuroleptic Malignant Syndrome (NMS), Tardive Dyskinesia (TD), QT prolongation, seizures, agranulocytosis, suicidal thoughts/behaviors, priapism, hyperglycemia, sudden cardiac death. ### Key Drug Interactions - **CYP3A4 Inhibitors (e.g., ketoconazole)**: Significantly increases quetiapine levels; reduce quetiapine dose. - **CYP3A4 Inducers (e.g., phenytoin, carbamazepine)**: Significantly decreases quetiapine levels; increase quetiapine dose or use alternative. - **CNS Depressants (e.g., alcohol, benzodiazepines)**: Additive sedative effects; use with caution. - **QT-prolonging drugs (e.g., class IA/III antiarrhythmics)**: Increased risk of QT prolongation; avoid co-administration if possible, monitor ECG. ## Monitoring & Follow-up - **Before Treatment**: Baseline weight, height, BMI, blood pressure, fasting plasma glucose, lipids (total cholesterol, HDL, LDL, triglycerides), LFTs, ECG (if cardiac risk factors). - **During Treatment**: - **Weight/BMI**: Weekly for first few weeks, then monthly. - **Blood Pressure**: Regularly, especially during initial titration. - **Fasting Glucose/Lipids**: At 3 months, then annually. - **ECG**: Periodically if cardiac risk factors or with QT-prolonging drugs. - **LFTs**: Periodically in patients with hepatic impairment. - **Clinical Signs**: Monitor for NMS (fever, rigidity, mental status change), TD (uncontrolled movements), orthostatic hypotension symptoms, suicidal ideation, changes in mental status. ## Clinical Pearls - 💡 **Administer XR formulations without food or with a light meal (<300 calories)** to avoid increased absorption and potential adverse effects. - 💡 **Initial dose should be given at bedtime** due to significant somnolence, especially for depression indications. - 💡 **Orthostatic hypotension is common during initiation** due to alpha-1 blockade; advise patients to rise slowly. - 💡 **Patients may experience significant weight gain** and metabolic changes; counsel on diet and exercise. - 💡 **"Baby Seroquel" for insomnia is off-label** and generally discouraged due to significant metabolic risks and side effects. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.