- Last edited on October 28, 2021
Quetiapine (Seroquel)
Primer
Quetiapine (Trade name: Seroquel) is an antipsychotic in the atypical antipsychotic class used in the treatment of schizophrenia, bipolar disorder, and major depressive disorder. It is also commonly used off-label for numerous other indications and psychiatric disorders.
Pharmacokinetics
See also article: Introduction to Pharmacology
Pharmacokinetics of Quetiapine
Absorption | Tmax = 1-3 hours |
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Distribution | |
Metabolism | |
Elimination | |
Half-life | Half-life = 6-12 hours |
See also article: Cytochrome (CYP) P450 Metabolism
Quetiapine: Cytochrome P450 Metabolism
Substrate of (Metabolized by) | |
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Induces | |
Inhibits |
Pharmacodynamics
Mechanism of Action
See also: Mechanism of Action of Quetiapine
- 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.
Toxicity
Indications
-
- 600 mg PO daily is an effective target dose in treating acute mania for bipolar I disorder[4]
Dosing (Immediate vs. Extended Release)
Quetiapine Immediate Release (IR) vs. Extended Release (XR)
Generic name | Quetiapine Immediate Release (IR) | Quetiapine Extended Release (XR) |
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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 |
Titration
- 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]
Formulations
- Quetiapine comes in oral and liquid formulations
Monitoring
Contraindications
Absolute
Relative
Drug-Drug Interactions
Side Effects
Adverse Events
- 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
Clinical Pearls
Special Populations
Geriatric
See main article: Geriatric Pharmacology
Pediatric
See main article: Pediatric Pharmacology
Obstetric and Fetal
See main article: Obstetric and Fetal Pharmacology
Medically Ill
See main article: Psychotropic Dosing in the Medically Ill
Resources
References
2)
Kapur, S., & Seeman, P. (2000). Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. Journal of Psychiatry and Neuroscience, 25(2), 161.
3)
Schatzberg, AF, Nemeroff, C . The American Psychiatric Publishing Textbook of Psychopharmacology. 4th ed. American Psychiatric Publishing, 2009.
4)
Vieta, E., Goldberg, J. F., Mullen, J., Vågerö, M., & Paulsson, B. (2007). Quetiapine in the treatment of acute mania: Target dose for efficacious treatment. Journal of affective disorders, 100, S23-S31.
5)
Young, A. H., McElroy, S. L., Bauer, M., Philips, N., Chang, W., Olausson, B., ... & Brecher, M. (2010). A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I). The Journal of clinical psychiatry, 71(2), 150-162.
6)
Riesenberg, R. A., Baldytcheva, I., & Datto, C. (2012). Self-reported sedation profile of quetiapine extended-release and quetiapine immediate-release during 6-day initial dose escalation in bipolar depression: a multicenter, randomized, double-blind, phase IV study. Clinical therapeutics, 34(11), 2202-2211.