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Use of High Doses of Quetiapine in Bipolar Disorder Episodes are not Linked to High Activity of Cytochrome P4503A4 and/or Cytochrome P4502D6

Khazaal, Yasser ; Preisig, Martin ; Chatton, Anne ; Kaufmann, Nadine ; Bilancioni, Romain ; Eap, Chin

In: Psychiatric Quarterly, 2013, vol. 84, no. 3, p. 329-335

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    Title
    • Use of High Doses of Quetiapine in Bipolar Disorder Episodes are not Linked to High Activity of Cytochrome P4503A4 and/or Cytochrome P4502D6
    Author
    • Khazaal, Yasser. Geneva University Hospitals, Grand pré, 70 C, 1206, Geneva, Switzerland
    • Preisig, Martin. University Hospital Center and University of Lausanne, Lausanne, Switzerland
    • Chatton, Anne. Geneva University Hospitals, Grand pré, 70 C, 1206, Geneva, Switzerland
    • Kaufmann, Nadine. University Hospital Center and University of Lausanne, Lausanne, Switzerland
    • Bilancioni, Romain. University Hospital Center and University of Lausanne, Lausanne, Switzerland
    • Eap, Chin. Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, University Hospital Lausanne, Prilly-Lausanne, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Psychiatric Quarterly, 2013, vol. 84, no. 3, p. 329-335. Springer US; http://www.springer-ny.com
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:320386
    Summary
    The use of quetiapine for treatment of bipolar disorders at a higher dosage than the licensed range is not unusual in clinical practice. Quetiapine is predominantly metabolised by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2D6. The large interindividual variability of those isozyme activities could contribute to the variability observed in quetiapine dosage. The aim of the present study is to evaluate if the use of high dosages of quetiapine in some patients, as compared to patients treated with a dosage in the licensed range (up to 800mg/day), could be explained by a high activity of CYP3A4 and/or of CYP2D6. CYP3A4 activities were determined using the midazolam metabolic ratio in 21 bipolar and schizoaffective bipolar patients genotyped for CYP2D6. 9 patients were treated with a high quetiapine dosage (mean±SD, median; range: 1467±625, 1200; 1000-3000mg/day) and 11 with a normal quetiapine dosage (433±274, 350; 100-800mg/day). One patient in the high dose and one patient in the normal dose groups were genotyped as CYP2D6 ultrarapid metabolizers. CYP3A4 activities were not significantly different between the two groups (midazolam metabolic ratio: 9.4±8.2; 6.2; 1.7-26.8 vs 3.9±2.3; 3.8; 1.5-7.6, in the normal dose group as compared to the high dose group, respectively, NS). The use of high quetiapine dosage for the patients included in the present study cannot be explained by variations in pharmacokinetics parameters such as a high activity of CYP3A4 and/or of CYP2D6