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Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I 2  = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes., (© 2024. The Author(s).)

Introduction: Kidney transplantation from a living donor is the treatment of choice for end- stage kidney disease. Psychological implications of living kidney donation are of great importance, both during preliminary psychiatric assessment and post-donation follow-up. The identification of risk factors worsening the psychological well-being of living kidney donors (LKDs), before and after donation, remains challenging in terms of research., Methods: At the University Hospitals of Geneva (HUG), our clinical observations and practice compelled us to establish post-donation follow-ups for LKDs at 6 months and 1 year. Pre-and post-donation sociodemographic, physical, psychological, and psychiatric data was collected from the medical records of 115 LKDs who underwent a complete physical and psychological evaluation during the period 2011-2018. We tested for any potential association between the variables under study., Results: A qualitative and retrospective analysis of this data highlighted the impact of postoperative factors, such as pain, fatigue, recipient-donor relationship, and fulfillment of donors' expectations, on the post-donation psychological well-being of LKDs., Discussion: With regard to these findings, regular post-donation follow-ups, optimal care of postoperative pain and fatigue, as well as a solid therapeutic alliance with LKDs remain key points for clinicians involved in the dynamic process of living kidney donation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Galani, Mazzola, Prada and Bondolfi.)