Exploring the role of drug-metabolising enzymes in antidepressant side effects
详细信息 查看全文
- 作者：Karen Hodgson ; Katherine E. Tansey ; Rudolf Uher…
- 关键词：Antidepressant ; Pharmacogenetics ; Side effects ; Drug metabolism ; Cytochrome P450 enzymes
- 刊名：Psychopharmacology
- 出版年：2015
- 出版时间：July 2015
- 年：2015
- 卷：232
- 期：14
- 页码：2609-2617
- 全文大小：823 KB
- 参考文献：Bull SA, Hunkeler EM, Lee JY, Rowland CR, Williamson TE, Schwab JR et al (2002) Discontinuing or switching selective serotonin-reuptake inhibitors. Ann Pharmacother 36(4):578-84PubMed View Article
Couchman L (2012) Turbulent flow chromatography in bioanalysis: a review. Biomed Chromatogr : BMC 26(8):892-05PubMed
Crawford AA, Lewis S, Nutt D, Peters TJ, Cowen P, O’Donovan MC et al (2014) Adverse effects from antidepressant treatment: randomised controlled trial of 601 depressed individuals. Psychopharmacology (Berl) 231(15):2921-931View Article
Dahl ML, Bertilsson L, Nordin C (1996) Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacology (Berl) 123(4):315-19View Article
de Leon J (2006) AmpliChip P450 test: personalized medicine has arrived in psychiatry. Expert Rev Mol Diagn 6(3):277-86PubMed View Article
Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39(2):175-91PubMed View Article
FDA (2001) Guidance for industry. Bioanalytical method validation. 2013
FDA (2011) FDA: drug interactions (P450 inhibitors and inducers). 2013
Freeman B, Smith N, Curtis C, Huckett L, Mill J, Craig IW (2003) DNA from buccal swabs recruited by mail: evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behav Genet 33(1):67-2PubMed View Article
Grasm?der K, Verwohlt P, Rietschel M, Dragicevic A, Müller M, Hiemke C et al (2004) Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol 60(5):329-36PubMed View Article
Hiemke C, Hartter S (2000) Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther 85(1):11-8PubMed View Article
Hodgson K, Tansey K, Dernovsek MZ, Hauser J, Henigsberg N, Maier W et al (2014) Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. J Psychopharmacol 28(2):133-41PubMed View Article
Huezo-Diaz P, Perroud N, Spencer EP, Smith R, Sim S, Virding S et al (2012) CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP. J Psychopharmacol (Oxford, England) 26(3):398-07View Article
Ingelman-Sundberg M (2004) Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 25(4):193-00PubMed View Article
Kennedy S, McIntyre R, Fallu A, Lam R (2002) Pharmacotherapy to sustain the fully remitted state. Journal of Psychiatry and Neuroscience 27(4):269-80
Kent JT (1982) Robust properties of likelihood ratio tests. Biometrika 69(1):19-7
Kirchheiner J, Brosen K, Dahl ML, Gram LF, Kasper S, Roots I et al (2001) CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand 104(3):173-92PubMed View Article
Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I et al (2004) Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 9(5):442-73PubMed View Article
Linder MW, Keck PE Jr (1998) Standards of laboratory practice: antidepressant drug monitoring. National Academy of Clinical Biochemistry. Clin Chem 44(5):1073-084PubMed
Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K (1987). The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 334:1-00
Masand PS (2003) Tolerability and adherence issues in antidepressant therapy. Clinical Therapeutics 25(8):2289-304
Matchar DB, Thakur ME, Grossman I, McCrory DC, Orlando LA, Steffens DC et al. (2007) Testing for cytochrome P450 polymorphisms in adults with non-psychotic depression treated with selective serotonin reuptake inhibitors (SSRIs). Evid Rep Technol Assess (Full Rep), 2007/09/04 edn, pp 1-7
Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382-89PubMed View Article
Mrazek DA, Biernacka JM, O’Kane DJ, Black JL, Cunningham JM, Drews MS et al (2011) CYP2C19 variation and citalopram response. Pharmacogenet Genomics 21(1):1-PubMed Central PubMed View Article
Murphy GM Jr, Pollock BG, Kirshner MA, Pascoe N, Cheuk W, Mulsant BH et al (2001) CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression. Neuropsychopharmacology 25(5):737-43PubMed View Article
Olesen OV, Linnet K (1999) Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes. Pharmacol - 作者单位：Karen Hodgson (1)
Katherine E. Tansey (1)
Rudolf Uher (1) (3)
Mojca Zvezdana Dernov?ek (4)
Ole Mors (14) (5)
Joanna Hauser (6)
Daniel Souery (7)
Wolfgang Maier (8)
Neven Henigsberg (9)
Marcella Rietschel (10)
Anna Placentino (11)
Ian W. Craig (1)
Katherine J. Aitchison (1) (12)
Anne E. Farmer (1)
Richard J. B. Dobson (13) (2)
Peter McGuffin (1)
1. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
3. Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
4. University Psychiatric Clinic, Ljubljana, Slovenia
14. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
5. Research Department P, Aarhus University Hospital, Risskov, Denmark
6. Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznań, Poland
7. Laboratoire de Psychologie Médicale, Université Libre de Bruxelles; PsyPluriel - Centre Européan de Psychologie Médicale, Brussels, Belgium
8. Department of Psychiatry, University of Bonn, Bonn, Germany
9. Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia
10. Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany
11. Psychiatric Unit (UOP 23), Department of Mental Health, Biological Psychiatry Unit Spedali Civili Hospital of Brescia, IRCCS-FBF, Brescia, Italy
12. Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
13. NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK
2. Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Pharmacology and Toxicology
Psychiatry - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-2072
文摘
Rationale Cytochrome P450 enzymes are important in the metabolism of antidepressants. The highly polymorphic nature of these enzymes has been linked to variability in antidepressant metabolism rates, leading to hope regarding the use of P450 genotyping to guide treatment. However, evidence that P450 genotypic differences underlie the variation in treatment outcomes is inconclusive. Objectives We explored the links between both P450 genotype and serum concentrations of antidepressant with antidepressant side effects, using data from the Genome-Based Therapeutic Drugs for Depression Project (GENDEP), which is a large (n--68), pharmacogenetic study of depressed individuals treated with escitalopram or nortriptyline. Methods Patients were genotyped for the enzymes CYP2C19 and CYP2D6, and serum concentrations of both antidepressant and primary metabolite were measured after 8?weeks of treatment. Side effects were assessed weekly. We investigated associations between P450 genotypes, serum concentrations of antidepressants and side effects, as well as the relationship between P450 genotype and study discontinuation. Results P450 genotype did not predict total side effect burden (nortriptyline: n--51, p--.5638, β-??0.133, standard error (SE)--.229; escitalopram: n--40, p--.9627, β-??0.004, SE--.085), study discontinuation (nortriptyline n--84, hazard ratio (HR)--.300, p--.174; escitalopram n--76, HR--.870, p--.118) or specific side effects. Serum concentrations of antidepressant were only related to a minority of the specific side effects measured: dry mouth, dizziness and diarrhoea. Conclusions In this sample where antidepressant dosage is titrated using clinical judgement, P450 genotypes do not explain differences between patients in side effects with antidepressants. Serum drug concentrations appear to only explain variability in the occurrence of a minority of specific side effects.