Quetiapine (Seroquel)

Quetiapine (Seroquel)

HALF-LIFE: Quetiapine 6-7 hours; Norquetiapine (active metabolite) 
STARTING DOSE: IR: 25mg-50mg PO BID; XR: 300mg PO QHS
TARGET DOSING RANGE: 50mg-800mg daily
BEST TIME TO DOSE: Bedtime
HOW TO DOSE: 
 >> IR: Initial 25mg-50mg PO BID. Increase by 50mg-100mg per day 
every 1-4 days.
>> XR: Initial 150mg-300mg PO QHS. Increase by 150mg-300mg per day every 2-7 days.
>> Max dose 800mg/day (some patients may require doses of up to 1200mg/day)
PREGNANCY: Minimal data on safety. 
BREASTFEEDING: Minimal data on safety. 
FDA INDICATIONS:
1)  Schizophrenia, 13yo and older
2) Bipolar disorder (manic/mixed), 10yo and older
3) Bipolar depression
4) Adjunctive treatment in Unipolar Major Depression

ADDITIONAL INFORMATION

  • Norquetiapine is the active metabolite of quetiapine and has antagonist effects at NET (norepinephrine transporter), 5HT7, 5HT2C, and α2 receptors as well as partial agonist effects at 5HT1A receptors
  • Different Drug Formulations
    • (IR): 300mg dose peaks to 90% D2 occupancy then rapidly declines
    • (IR): 800mg dose only occupies D2 at >60% for 12 hours
    • (XR): 300mg dose peaks slowly to 80% after 6 hours and stays above 60% for another 6 hours
    • (XR): 800mg dose fully effective D2 occupancy for 24 hours with less peak sedation
  • Quetiapine is a different drug at different doses
    • Hypnotic (H1) dose: 50mg
    • Antidepressant (5HT2C, NET) dose: 300mg
    • Antipsychotic (D2) dose: 800mg

  • Very Low EPS Risk
  • Very low risk for prolactin elevation
  • Weak D2 antagonism makes quetiapine a preferred antipsychotic for Parkinson’s (although pimavanserin is a better option)
  • Weight Gain is common due to antagonism at H1 and 5HT2C receptors
  • Sedation is common due to antagonism at α1 and H1 receptors
  • Orthostatic hypotension is common due to antagonism at α1 receptors
  • Intermediate-high cardio-metabolic risk (↑triglycerides, insulin resistance)
  • Metabolized by CYP3A4 and CYP2D6

References:

  1. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  2. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  3. Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  4. J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  5. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  6. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  7. Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  8. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  9. Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.