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Quetiapine

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Quetiapine, Seroquel

  • See Also
  1. Quetiapine Overdose
  2. Antipsychotic Medication
  3. Psychosis
  • Class
  1. Atypical Antipsychotic (Second Generation Antipsychotic)
  2. Neuroleptic
  3. Dibenzothiazepine Antipsychotic
  • Mechanism
  1. Stronger Antagonist at Serotonin 5HT2 receptors than Dopamine D2 receptors
  2. Potent alpha-1 Adrenergic ReceptorAntagonist (risk of Hypotension)
  3. Weak Antagonist at Dopamine (D2), Histamine muscarinic (M1) and Serotonin (5HT-1A) with risk of sedation
  • Indications
  1. Schizophrenia
  2. Psychosis in Dementia
  3. Bipolar Disorder
  4. Mania
  5. Major Depression (adjunct)
  6. Autism (not FDA approved)
  7. Insomnia (not FDA approved)
  8. Obsessive Compulsive Disorder (not FDA approved)
  9. Generalized Anxiety Disorder (not FDA approved)
  • Precautions
  1. Use lower doses and slower titration in the elderly and liver dysfunction
    1. Start at 25 mg/day and increase by no more than 25 to 50 mg/day
  2. Restart dose titration if Quetiapine was stopped for more than 7 days
  3. Low risk of Tardive Dyskinesia and Extrapyramidal Side Effects
  1. Adults (or Children age 13 to 17 years) Regular Immediate Release Oral Tablets
    1. Initial: 25 mg orally twice daily
    2. Increase in 25-50 mg/day increments divided 2-3 times daily
    3. Example of a more rapid titration
      1. Day 1: Take 25 mg orally twice daily
      2. Day 2: Take 50 mg orally twice daily
      3. Day 3: Take 100 mg orally twice daily
      4. Day 4: Take 150 mg orally twice daily
      5. Day 5: Take 200 mg orally twice daily
    4. Target: 300-400 mg/day orally divided twice to three times daily
    5. Maximum dose: 800 mg/day
  2. Adults (or Children age 13 to 17 years) Sustained Release Tablets (Seroquel XR)
    1. Avoid taking Sustained Release Tablets with food
    2. May start at up to 300 mg orally each evening at bedtime
      1. May increase up to 300 mg/day
    3. Example of dose titration
      1. Dose 1: Take 50 mg orally at bedtime
      2. Dose 2: Take 100 mg orally at bedtime
      3. Dose 3: Take 200 mg orally at bedtime
      4. Dose 4: Take 300 mg orally at bedtime
      5. Dose 5: Take 400 mg orally at bedtime
    4. Target 400 to 800 mg/day
    5. Maximum 800 mg/day
  • Dosing
  • Acute Bipolar Mania or Mixed Disorder
  1. Adults Regular (or Children age 13 to 17 years) Immediate Release Oral Tablets
    1. Day 1: Start 50 mg orally twice daily
    2. Day 2: Take 100 mg orally twice daily
    3. Day 3: Take 150 mg orally twice daily
    4. Day 4: Take 200 mg orally twice daily
    5. Day 5: Take 300 mg orally twice daily
    6. Day 6: Take 400 mg orally twice daily
    7. Target: 400 to 600 mg/day (up to 800 mg/day in adults)
    8. Maximum: 600 mg/day (up to 800 mg/day in adults)
  2. Adults (or Children age 13 to 17 years) Extended Release Oral Tablets (Seroquel XR)
    1. Avoid taking Sustained Release Tablets with food
    2. May consider rapid start higher dosing in adults (or use titrating dose below)
      1. Day 1: 300 mg orally at bedtime
      2. Day 2: 600 mg orally daily bedtime
    3. Titrate to dose in children age 13 to 17 years
      1. Day 1: Start 50 mg orally at bedtime
      2. Day 2: Take 100 mg orally at bedtime
      3. Day 3: Take 200 mg orally at bedtime
      4. Day 4: Take 300 mg orally at bedtime
      5. Day 5: Take 400 mg orally at bedtime
    4. Target: 400 to 600 mg orally daily each evening (up to 800 mg/day in adults)
    5. Maximum: 600 mg/day (up to 800 mg/day in adults)
  1. Adults Extended Release Oral Tablets (Seroquel XR)
    1. Titrate rapidly as below in Bipolar Depression (more gradually in Major Depression)
    2. Day 1: Start 50 mg orally at bedtime
    3. Day 2: Take 100 mg orally at bedtime
    4. Day 3: Take 200 mg orally at bedtime
    5. Day 4: Take 300 mg orally at bedtime
    6. Continue 300 mg orally daily at bedtime
    7. Maximum: 30 mg/day
  • Dosing
  • Miscellaneous
  1. Adults with Refractory Insomnia (not FDA approved)
    1. Start 50 mg orally at bedtime
    2. Titrate as needed to effect
    3. Maximum: 400 mg
  2. Elderly Regular Oral Tablets
    1. Initial dose: 12.5 mg orally at bedtime
    2. Titrate dose every few days (caution due to sedation)
  • Pharmacokinetics
  • Quetiapine Regular Tablets
  1. Use lower doses and slower titration in the elderly and liver dysfunction
  2. Lipophilic
  3. Large volume of distribution (10 L/kg +/-4 L/kg)
  4. Plasma Protein binding: 83%
  5. Not dialyzable
  6. Half-Life: 6 hours
  7. Peak Levels: 2-3 hours
  8. Metabolism: CYP 3A4
  • Adverse Effects
  • General
  1. Sedation
  2. Headache
  3. Orthostatic Hypotension
  4. Cataract formation
  5. Dry Mouth (although Anticholinergic effects are minimal with Quetiapine)
  6. Weight gain
  7. Hyperglycemia and increased risk of Diabetes Mellitus
  8. Neuroleptic Malignant Syndrome
  9. QTc Prolongation
  1. See Quetiapine Overdose
  2. Somnolence
  3. Tachycardia
  4. Hypotension
  • Drug Interactions
  1. Metabolized by CYP3A4
    1. Decrease dose to one-sixth of typical dose when on strong CYP3A4 inhibitors
    2. Increase dose (as much as 5 fold) when on stong CYP3A4 inducers
  2. Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
    1. Clarithromycin
    2. Erythromycin
    3. Grapefruit juice
    4. Fluconazole
    5. Itraconazole
    6. Ketoconazole
    7. Quinidine
  3. Decrease Antipsychotic levels (lower efficacy)
    1. Barbiturates
    2. Carbamazepine
    3. Phenytoin
    4. Rifampin
    5. Theophylline
  4. Other effects
    1. Avoid concurrent use of other medications prolonging QT Interval
      1. See Prolonged QT Interval due to Medication
  • Safety
  1. Pregnancy Category C
  2. Avoid in Lactation
  • Monitoring
  1. See Quetiapine Overdose
  2. See Antipsychotic
  3. Screen for Cataract formation every 6 months
  4. Consider EKG, Electrolyte and Magnesium monitoring due to QT Interval prolongation risk
  5. Monitor weight, Fasting Glucose and Serum Triglycerides (at baseline and periodically)
  • Resources
  1. Quetiapine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6b7d7d2f-a50b-8e21-2de4-ccc102016384
  • References
  1. (2016) Med Lett Drugs Ther 58(1510): 160-5
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 42-3
  3. Otter and Tomaszewski (2018) Crit Dec Emerg Med 32(8): 32
  4. Hamilton (2020) Tarascon Pocket Pharmacopoeia