Related Experiment Video
Updated: May 28, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D
S L Clark1, D E Adkins, K Aberg
1Center for Biomarker Research and Personalized Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0581, USA. slclark2@vcu.edu
Background:
Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.
Method:
We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries.
Results:
Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p = 4.98 × 10(-7), q = 0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1.
Conclusions:
Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenomics: Identification of New Drug Targets
Antidepressant Drugs: MAOIs and Other Agents
Antidepressant Drugs: Overview
Factors Affecting Drug Response: Overview
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

