TY - JOUR
T1 - Association between CYP metabolizer phenotypes and selective serotonin reuptake inhibitors induced weight gain: a retrospective cohort study
AU - Ricardo-Silgado, Maria L.
AU - Singh, Sneha
AU - Cifuentes, Lizeth
AU - Decker, Paul A.
AU - Gonzalez-Izundegui, Daniel
AU - Moyer, Ann M.
AU - Hurtado, Maria D.
AU - Camilleri, Michael
AU - Bielinski, Suzette J.
AU - Acosta, Andres
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Prescription medications such as selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, are associated with weight gain. The role of pharmacogenomics in predicting SSRI-induced weight gain is unclear. Methods: In this retrospective cohort study from participants in the Mayo Clinic RIGHT study who were prescribed citalopram, paroxetine, sertraline, or fluoxetine, our aim was to evaluate the association of metabolizer phenotype and total body weight after 6 months of SSRIs initiation. We evaluated the metabolizer phenotypes (poor/intermediate, normal, and rapid/ultra-rapid) of the cytochromes P450 enzymes genes: CYP2C9, CYP2C19, and CYP2D6 known to influence the metabolism of SSRI medications: CYP2C19 for citalopram, CYP2D6 for paroxetine, CYP2D6 and CYP2C19 for sertraline, and CYP2D6 and CYP2C9 fluoxetine. In addition, we assessed the association of metabolizer phenotype and total body weight change at six months following SSRI prescription using parametric analysis of covariance adjusted for baseline body weight and multivariate regression models. Results: CYP2C19 poor/intermediate metabolizers prescribed citalopram gained significantly more weight than normal or rapid/ultra-rapid metabolizers at 6 months (TBWG %: 2.6 [95% CI 1.3—4.1] vs. 0.4 [95% CI -0.5 – 1.3] vs. -0.1 [-95% CI -1.5—1.1]; p = 0.001). No significant differences in weight outcomes at six months of treatment with paroxetine, sertraline, or fluoxetine were observed by metabolizer status. Conclusions: Weight gain observed with citalopram may be mediated by CYP2C19 metabolizer status.
AB - Background: Prescription medications such as selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, are associated with weight gain. The role of pharmacogenomics in predicting SSRI-induced weight gain is unclear. Methods: In this retrospective cohort study from participants in the Mayo Clinic RIGHT study who were prescribed citalopram, paroxetine, sertraline, or fluoxetine, our aim was to evaluate the association of metabolizer phenotype and total body weight after 6 months of SSRIs initiation. We evaluated the metabolizer phenotypes (poor/intermediate, normal, and rapid/ultra-rapid) of the cytochromes P450 enzymes genes: CYP2C9, CYP2C19, and CYP2D6 known to influence the metabolism of SSRI medications: CYP2C19 for citalopram, CYP2D6 for paroxetine, CYP2D6 and CYP2C19 for sertraline, and CYP2D6 and CYP2C9 fluoxetine. In addition, we assessed the association of metabolizer phenotype and total body weight change at six months following SSRI prescription using parametric analysis of covariance adjusted for baseline body weight and multivariate regression models. Results: CYP2C19 poor/intermediate metabolizers prescribed citalopram gained significantly more weight than normal or rapid/ultra-rapid metabolizers at 6 months (TBWG %: 2.6 [95% CI 1.3—4.1] vs. 0.4 [95% CI -0.5 – 1.3] vs. -0.1 [-95% CI -1.5—1.1]; p = 0.001). No significant differences in weight outcomes at six months of treatment with paroxetine, sertraline, or fluoxetine were observed by metabolizer status. Conclusions: Weight gain observed with citalopram may be mediated by CYP2C19 metabolizer status.
KW - CYP metabolizer phenotypes
KW - Pharmacogenomics
KW - Weight gain
UR - http://www.scopus.com/inward/record.url?scp=85134767743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85134767743&partnerID=8YFLogxK
U2 - 10.1186/s12916-022-02433-x
DO - 10.1186/s12916-022-02433-x
M3 - Article
C2 - 35879764
AN - SCOPUS:85134767743
SN - 1741-7015
VL - 20
JO - BMC Medicine
JF - BMC Medicine
IS - 1
M1 - 261
ER -