The Effect of ABCB1 Polymorphisms on the Efficacy of Antidepressants

This scoping review investigates the association between ABCB1 polymorphisms and antidepressant efficacy in humans. A systematic search identified 630 records, of which 58 met the inclusion criteria, resulting in 42 unique studies (five randomised controlled trials (RCTs), two randomised studies (non-RCTs), 30 prospective cohort studies, three case-control studies, one cross-sectional clinical study and one phase I clinical trial). These studies examined single nucleotide polymorphisms (SNPs) in or near the ABCB1 gene and their association with antidepressant treatment response. Of the 42 studies, 30 focused on rs1045642, the most extensively studied SNP. Among these, only 20% reported statistically significant associations. Beyond rs1045642, rs2032582 and rs1128503 were also frequently studied, but statistically significant associations were reported in only a minority of cases (28% and 13%, respectively), often with conflicting directions. Haplotype analyses involving all three SNPs (the TTT haplotype) showed mixed results. Results were variable across antidepressants, likely due to overlapping pharmacokinetic pathways. Methodological differences, including study design, sample sizes and definitions of remission, likely contribute to these inconsistencies. This review highlights the complexity of linking ABCB1 polymorphisms to antidepressant treatment response and suggests the need for standardised methodologies and larger, diverse populations in future studies. Haplotype analyses could provide deeper insights and enhance personalised treatment strategies.