CYP2D6 poor metabolizer status might be associated with better response to risperidone treatment

被引:27
作者
Almoguera, Berta [1 ,3 ]
Riveiro-Alvarez, Rosa [1 ,3 ]
Lopez-Castroman, Jorge [2 ,8 ]
Dorado, Pedro [8 ,9 ]
Vaquero-Lorenzo, Concepcion [4 ]
Fernandez-Piqueras, Jose [3 ,4 ]
LLerena, Adrian [8 ,9 ]
Abad-Santos, Francisco [5 ,6 ]
Baca-Garcia, Enrique [2 ,8 ,10 ]
Dal-Re, Rafael [7 ]
Ayuso, Carmen [1 ,3 ]
机构
[1] Fdn Jimenez Diaz Univ Hosp, IIS, Dept Genet & Genom, Madrid 28040, Spain
[2] Fdn Jimenez Diaz Univ Hosp, IIS, Dept Psychiat, Madrid 28040, Spain
[3] CIBERER ISCIII, Madrid, Spain
[4] Autonomous Univ Madrid, Dept Biol, CBMSO, CSIC, E-28049 Madrid, Spain
[5] La Princesa Univ Hosp, IIS Princesa, Dept Clin Pharmacol, Madrid, Spain
[6] CIBEREHD ISCIII, Madrid, Spain
[7] Rey Juan Carlos Univ, Sch Hlth Sci, Dept Prevent Med Publ Hlth & Med Immunol & Microb, Madrid, Spain
[8] CIBERSAM ISCIII, Madrid, Spain
[9] Extremadura Univ Hosp & Med Sch, Clin Res Ctr, CICAB, Badajoz, Spain
[10] Columbia Univ, Dept Psychiat, New York, NY USA
关键词
CYP2D6; effectiveness; MDR1; pharmacogenetics; risperidone; schizophrenia; SCHIZOPHRENIA; PHENOTYPE;
D O I
10.1097/FPC.0b013e3283659a94
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The variability in the antipsychotic response is, to some extent, genetically determined. Several studies have attempted to establish a role for genetic variation in genes coding pharmacokinetic and pharmacodynamic targets, but to date, no definite genetic predictive marker has been identified. We aimed to explore the putative role of 19 genetic variants and risperidone clinical improvement in 76 White schizophrenic inpatients, measured as change in Positive and Negative Syndrome Scale (PANSS). CYP2D6 poor metabolism was significantly associated with greater clinical improvement in total PANSS and a trend was also found for MDR1 3435C>T to higher total PANSS scores in 3435T carriers. This study suggests the importance that genetic variability on pharmacokinetic factors may have in risperidone response and gives evidence for the need for further investigation in order to establish the actual predictive value and clinical utility that CYP2D6 genotyping might have in risperidone therapy management. (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
引用
收藏
页码:627 / 630
页数:4
相关论文
共 8 条
  • [1] Association of common genetic variants with risperidone adverse events in a Spanish schizophrenic population
    Almoguera, B.
    Riveiro-Alvarez, R.
    Lopez-Castroman, J.
    Dorado, P.
    Vaquero-Lorenzo, C.
    Fernandez-Piqueras, J.
    Llerena, A.
    Abad-Santos, F.
    Baca-Garcia, E.
    Dal-Re, R.
    Ayuso, C.
    [J]. PHARMACOGENOMICS JOURNAL, 2013, 13 (02) : 197 - 204
  • [2] Bartecek R, 2012, NEUROENDOCRINOL LETT, V33, P236
  • [3] The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation
    de Leon, J
    Susce, MT
    Pan, RM
    Fairchild, M
    Koch, WH
    Wedlund, PJ
    [J]. JOURNAL OF CLINICAL PSYCHIATRY, 2005, 66 (01) : 15 - 27
  • [4] The CYP2D6 activity score: Translating genotype information into a qualitative measure of phenotype
    Gaedigk, A.
    Simon, S. D.
    Pearce, R. E.
    Bradford, L. D.
    Kennedy, M. J.
    Leeder, J. S.
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 2008, 83 (02) : 234 - 242
  • [5] THE POSITIVE AND NEGATIVE SYNDROME SCALE (PANSS) FOR SCHIZOPHRENIA
    KAY, SR
    FISZBEIN, A
    OPLER, LA
    [J]. SCHIZOPHRENIA BULLETIN, 1987, 13 (02) : 261 - 276
  • [6] Definitions of response and remission in schizophrenia: recommendations for their use and their presentation
    Leucht, S.
    Davis, J. M.
    Engel, R. R.
    Kissling, W.
    Kane, J. M.
    [J]. ACTA PSYCHIATRICA SCANDINAVICA, 2009, 119 : 7 - 14
  • [7] LLerena A, 2013, PHARMACOGENOMICS, V14, P177, DOI [10.2217/PGS.12.201, 10.2217/pgs.12.201]
  • [8] Intuitive pharmacogenetics: spontaneous risperidone dosage is related to CYP2D6, CYP3A5 and ABCB1 genotypes
    Mas, S.
    Gasso, P.
    Alvarez, S.
    Parellada, E.
    Bernardo, M.
    Lafuente, A.
    [J]. PHARMACOGENOMICS JOURNAL, 2012, 12 (03) : 255 - 259