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CLINICAL TRIAL article

Front. Pharmacol.

Sec. Pharmacogenetics and Pharmacogenomics

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1626654

Clinicians' experience on the effectiveness of pharmacotherapy in patients with first-episode depression: A randomized controlled trial based on pharmacogenomics

Provisionally accepted
Jie  TongJie TongJie  YuanJie YuanYu  QinYu QinNa  ZhuNa ZhuTT  ZhangTT ZhangXiaochun  ZhuXiaochun ZhuYuanyuan  XuYuanyuan XuMeilin  LiuMeilin LiuJie  ZhangJie ZhangXirong  SunXirong Sun*
  • Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China

The final, formatted version of the article will be published soon.

Background: Due to differences in drug efficacy, the risk of adverse reactions, and individual differences between patients, clinicians face significant challenges in terms of selecting drugs for the treatment of depression. However, no previous studies have compared the efficacy of antidepressant treatments between psychiatrists with different levels of experience based on pharmacogenomics approach.Methods: A total of 178 patients were recruited and randomly assigned to pharmacogenomics-guided treatment group or regular treatment control group. The control group was further divided into the senior doctor and the nonsenior doctor subgroups. All participants completed pharmacogenomic assessments at baseline. They also completed the 17-items Hamilton Depression Scale (HAM-D17), Dimensional Anhedonia Rating Scale (DARS), Perceived Deficits Questionnaire-Depression (PDQ-D), and Antidepressant Side Effect Checklist (ASEC) at baseline and at 4-week, 8-week, 16-week, and 32-week follow-ups. The study protocol was registered with ClinicalTrials.gov (NCT05669391).Results: Compared with the control group, pharmacogenomics-guided group presented significant differences in DARS and ASEC scores at 32 weeks (PBonferroni< .05), with significant time and group effect (P< .05). However, there was no significant difference in HAM-D17 and PDQ-D scores between the two groups at 32 weeks (PBonferroni> .05). The number of antidepressant changes at 32 weeks in the nonsenior doctor subgroup was significantly higher than that in the senior doctor subgroup (1.04 vs. 0.31, P= .005). There was no significant difference in the number of combined antidepressants, the number of patients who used somnifacients, HAM-D17 scores, DARS scores, PDQ-D scores, and ASEC scores between the two groups (P> .05). The number of antidepressant changes and HAM-D17 scores are 32-weeks were negatively correlated with the doctor's years of work experience (r=-0.25, P= .012; r=-0.29, P= .004; respectively).Pharmacogenomics-guided treatment can effectively mitigate the occurrence of anhedonia and side effects in patients with first-episode depression. Higher level of clinical experience among psychiatrists can lead to significant reduction in the frequency of antidepressant drug changes, and the depressive symptoms at the endpoint are negatively correlated with the clinicians' work experience. Pharmacogenomics may reduce the influence of clinical experience on treatment outcomes in primary mental healthcare settings.

Keywords: psychiatrist, First-episode depression, Depression, FED, pharmacogenomics, PGx

Received: 11 May 2025; Accepted: 24 Jul 2025.

Copyright: © 2025 Tong, Yuan, Qin, Zhu, Zhang, Zhu, Xu, Liu, Zhang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xirong Sun, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China

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