Fig. 1: Study design overview.

Three data layers containing side effect information for the Estonian Biobank participants were used. The data layers ADEQ, MHoS, and EHR were merged and antidepressants users with distinct side effects and no side effects were retained. The sample was used to carry out analyses in different drug subgroups: 1) four drugs metabolised by CYP2C19 pooled for pharmacogenetic analysis; 2) all drugs combined and drug classes separately (SSRI; SNRI+Atyp.; TCA) for PGS analyses for psychiatric trait and trait-specific analyses; 3) meta-analysis with AGDS on individual drug-level. A subgroup analysis was carried out by restricting the sample to individuals with a recorded depression diagnosis. AD—antidepressant; PGS—polygenic score; MHoS—Estonian Biobank Mental Health online Survey; ADEQ—Estonian Biobank Adverse Drug Events Questionnaire (ADEQ); EHR—electronic health records; AGDS—Australian Genetics of Depression Study; TCA—tricyclic antidepressant; SSRI—selective serotonin reuptake inhibitor; SNRI+Atyp.—serotonin-norepinephrine reuptake inhibitor and atypical antidepressant. Created in BioRender. Kariis, H. (2024) https://BioRender.com/t02y173.