Quetiapine (Seroquel)

Pharmacokinetics of Quetiapine

Absorption Tmax = 1-3 hours
Half-life Half-life = 6-12 hours

Quetiapine: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
  • Quetiapine is a:
    • Partial agonist
      • Serotonin 5-HT1A
    • Antagonist at:
      • Serotonin 5-HT2 (a key feature of all atypical antipsychotics)
      • Dopamine D1 and D2
      • Histamine H1 (antihistaminergic effects cause sedation)
      • Adrenergic alpha 1 and alpha 2 receptors (causes hypotension)
  • Of all antipsychotics, quetiapine (followed by clozapine) has the lowest affinity for the D2 receptor.[1] It dissociates the quickest from the D2 receptor, in about 15 seconds (this has been referred to the “kiss and run” hypothesis).[2][3]
    • As a result, these rapidly dissociating atypical antipsychotics have a very low incidence of EPS.

Quetiapine Immediate Release (IR) vs. Extended Release (XR)

Generic name Quetiapine Immediate Release (IR) Quetiapine Extended Release (XR)
Tradename Seroquel IR Seroquel XR
Dosage Strengths 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, 400 mg tablets 50 mg, 150mg, 200mg, 300mg, 400mg tablets
Half-life Shorter Longer
Dosing BID dosing Once daily dosing
Starting Dose (Bipolar Mania) 50 mg BID (increase by 100-200 mg/day) 300 mg PO daily (can increase by 300 mg/day)
Target Dose (Bipolar Mania) 400-800 mg PO daily[5] 400-800 mg PO daily
Advantages May be more beneficial in acute mania and psychosis due to more sedating features Faster dose titration and less sedating.[6]
Disadvantages More sedating Lower side effect profile
  • Sedation and weight gain can be dose limiting factors in the use of quetiapine. In this case, if one were to use this approach, one should start at a low dose of 25 mg PO qHS and increase as indicated and tolerated in 25 mg increments every 2-3 weeks. Maximum dose can go up to 1200mg.
  • On inpatient units, if using quetiapine for psychosis or mania, rapid increases by 100 to 200mg/day is OK.[7]
  • Quetiapine comes in oral and liquid formulations
  • There does not appear to be a bleeding risk, however, there are other possible haematological side effects (i.e., leucopenia and neutropenia)
    • CBC should be monitored
  • QTc prolongation is also possible, though relatively low risk
3) Schatzberg, AF, Nemeroff, C . The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed. American Psychiatric Publishing, 2009.