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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

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Abstract

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 800 mg/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; 1000–3000 mg/day) and 11 with a normal quetiapine dosage (433 ± 274, 350; 100–800 mg/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.

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Acknowledgments

The authors thank the editorial assistance of Mrs. V. Sari, and the bibliographical help of Mrs. M. Gobin and Mrs. E. Retamales. Prof Eap received during the period 1995-2012 research support from Astra Zeneca, Eli Lily, Fujisawa, Janssen Cilag, Novartis, Sandoz, SmithKline Beecham, Bristol-Myers Squibb and Wyeth. He received honoraria for conferences or teaching CME courses from Astra Zeneca, Bristol-Myers Squibb, Eli Lily, Essex Chemie, Glaxo-Smith Kline, Janssen-Cilag, Lundbeck, Novo Nordisk, Organon, Sandoz, Advisis. Dr Yasser Khazaal received during the period 2002-2012 research support from Astra Zeneca and Eli Lily. He received honoraria for conferences or teaching CME courses from Astra Zeneca, Bristol-Myers Squibb, Eli Lily and Lundbeck.

Conflict of interest

The other authors declare that they have no competing interests in relation to the present study.

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Authors and Affiliations

  1. Geneva University Hospitals, Grand pré, 70 C, 1206, Geneva, Switzerland

    Yasser Khazaal & Anne Chatton

  2. University Hospital Center and University of Lausanne, Lausanne, Switzerland

    Martin Preisig, Nadine Kaufmann & Romain Bilancioni

  3. Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, University Hospital Lausanne, Prilly-Lausanne, Switzerland

    Chin B. Eap

Authors
  1. Yasser Khazaal
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  2. Martin Preisig
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  3. Anne Chatton
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  4. Nadine Kaufmann
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  5. Romain Bilancioni
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  6. Chin B. Eap
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Correspondence to Yasser Khazaal.

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Khazaal, Y., Preisig, M., Chatton, A. et al. Use of High Doses of Quetiapine in Bipolar Disorder Episodes are not Linked to High Activity of Cytochrome P4503A4 and/or Cytochrome P4502D6. Psychiatr Q 84, 329–335 (2013). https://doi.org/10.1007/s11126-012-9248-9

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  • DOI: https://doi.org/10.1007/s11126-012-9248-9

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