TY - JOUR
T1 - ABCB1 Gene Variants and Antidepressant Treatment Outcomes
T2 - A Systematic Review and Meta-Analysis Including Results from the CAN-BIND-1 Study
AU - Magarbeh, Leen
AU - Hassel, Claudia
AU - Choi, Maximilian
AU - Islam, Farhana
AU - Marshe, Victoria S.
AU - Zai, Clement C.
AU - Zuberi, Rayyan
AU - Gammal, Roseann S.
AU - Men, Xiaoyu
AU - Scherf-Clavel, Maike
AU - Enko, Dietmar
AU - Frey, Benicio N.
AU - Milev, Roumen
AU - Soares, Claudio N.
AU - Parikh, Sagar V.
AU - Placenza, Franca
AU - Strother, Stephen C.
AU - Hassel, Stefanie
AU - Taylor, Valerie H.
AU - Leri, Francesco
AU - Blier, Pierre
AU - Farzan, Faranak
AU - Lam, Raymond W.
AU - Turecki, Gustavo
AU - Foster, Jane A.
AU - Rotzinger, Susan
AU - Kloiber, Stefan
AU - Kennedy, James L.
AU - Kennedy, Sidney H.
AU - Bousman, Chad A.
AU - Müller, Daniel J.
N1 - Publisher Copyright:
© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2023/7
Y1 - 2023/7
N2 - The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15–1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.
AB - The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15–1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.
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U2 - 10.1002/cpt.2854
DO - 10.1002/cpt.2854
M3 - Review article
C2 - 36681895
AN - SCOPUS:85149218956
SN - 0009-9236
VL - 114
SP - 88
EP - 117
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 1
ER -