ArticleEuropean journal of human genetics : EJHG2025
Genetic influences on antidepressant side effects: a CYP2C19 gene variation and polygenic risk study in the Estonian Biobank.
Article in European journal of human genetics : EJHG, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide meta-analyses of non-response to antidepressants provide insights into underlying molecular genetics and suggest potential pharmacotherapies.Molecular psychiatry · 2026Pooled it
- Obesity-related differences in amygdala and hippocampal volume and metabolism before and after a placebo-controlled antidepressant trial in major depressive disorder.Scientific reports · 2026Trial
- Cohort Profile Update: The Adverse Events Questionnaire of Medications and Vaccines (ADE-Q) in the Estonian Biobank.International journal of epidemiology · 2026Article
- preSCRIPT: Large-scale prescription search and annotation engine for pharmacogenomic studies.Pharmacological reports : PR · 2026Article
- Large-scale analysis demonstrates the influence of CYP2C19 genotype on specific SSRI side effects.The pharmacogenomics journal · 2026Article
- CYP2C19 Genotype is Associated with Citalopram Treatment Outcomes in a Real-World Setting.Clinical pharmacology and therapeutics · 2026Article
- Pharmacokinetic recall study of Estonian Biobank participants with novel genetic variants in CYP2C19 and CYP2D6.NPJ genomic medicine · 2026Article
- Personalizing Antidepressant Therapy: Integrating Pharmacogenomics, Therapeutic Drug Monitoring, and Digital Tools for Improved Depression Outcomes.Journal of personalized medicine · 2025Review
- CGRP-targeted therapy fulfilling the treatment gap in medication-underuse setting: a retrospective cohort study at a tertiary headache center in Thailand, a lower-middle-income country.The journal of headache and pain · 2025Article
- Uncertainty, ethics, and progress in genomic medicine.European journal of human genetics : EJHG · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Antidepressant side effects are prevalent, leading to significant treatment discontinuity among patients. A deeper understanding of the underlying mechanisms could help identify individuals at risk of side effects and improve treatment outcomes.We aim to investigate the role of genetic variation in CYP2C19 and polygenic scores (PGS) for psychiatric and side effect-related phenotypes in experiencing antidepressant side effects.We pooled Estonian Biobank data from the Mental Health online Survey (N = 86,244), the Adverse Drug Events Questionnaire (N = 49,366) and from unstructured electronic health records using natural language processing (N = 206,066) covering 25 common side effects. The results were meta-analysed with previously published results from the Australian Genetics of Depression Study. Among 13,729 antidepressant users, 52.0% reported side effects. In a subgroup of 9,563 individuals taking antidepressants metabolised by CYP2C19, poor metabolisers had 49% higher odds of reporting a side effect (OR = 1.49, 95%CI = 1.09-2.04), while ultrarapid metabolisers had 17% lower odds (OR = 0.83, 95%CI = 0.70-0.99) compared to normal metabolisers. PGSs for schizophrenia and depression showed the most associations with overall and specific side effects. PGSs for higher body mass index (BMI), anxiety, and systolic blood pressure were associated with respective side effects among any antidepressant and selective serotonin reuptake inhibitor (SSRI) users. Meta-analysis confirmed robust evidence linking a higher BMI PGS and weight gain across nine antidepressants and moderate evidence linking PGS for headache with headache from sertraline. Our findings underscore the role of genetic factors in experiencing antidepressant side effects and have potential implications for personalised medicine approaches to improve antidepressant treatment outcomes.
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