Zhang Yuan, Gao Yiyuan, Zou Yazhu, Ye Yu, Jiang Fugui, Wang Zuxing, Qiu Jian, Zou Zhili
Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Department of Pharmacy, Chengdu Eighth People's Hospital, Geriatric Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
BMJ Ment Health. 2025 Aug 25;28(1):e301726. doi: 10.1136/bmjment-2025-301726.
How effective is pharmacogenomic (PGx)-guided antidepressant treatment compared with treatment-as-usual (TAU) in major depressive disorder (MDD), and how do ethnicity, disease severity and genetic panel scope influence outcomes?
This systematic review and meta-analysis comprised 13 randomised controlled trials (2013-2024) comparing PGx-guided therapy with TAU in MDD. PubMed, Ovid Embase, Ovid Medline, Ovid PsycINFO and the Cochrane Library were searched up to December 2024. Outcomes included response and remission rates at 8 and 12 weeks. Subgroup analyses examined ethnicity and MDD severity. Cumulative meta-analyses assessed gene panel size. The pooled risk ratios (RRs) with 95% CIs were calculated to estimate the overall effect.
PGx-guided treatment significantly improved response rates at 8 weeks (RR 1.23, 95% CI 1.05 to 1.43) and 12 weeks (RR 1.29, 95% CI 1.17 to 1.43). Remission was significant at 8 weeks (RR 1.37, 95% CI 1.19 to 1.57) but not at 12 weeks (RR 1.56, 95% CI 0.93 to 2.61). Benefits appeared stronger in the Asian country subgroup compared with non-Asian country subgroup (interaction p=0.02), but this requires validation due to the smaller Asian country sample size. No significant subgroup differences were observed between the MDD not-specified and MDD difficult-to-treat subgroups, despite the latter demonstrating significant improvements in both response and remission rates with PGx-guided treatment compared with TAU at 8 weeks. Cumulative analyses showed effect sizes plateaued, with broader panels offering minimal incremental gains.
PGx-guided treatment seems to offer moderate benefits for antidepressant efficacy, with potential advantages in Asian and difficult-to-treat subgroups. Genetic and ethnic variability in drug metabolism underscores the need for population-specific approaches. While multigene panels show clinical benefits plateau, suggesting cost-benefit optimisation is critical. Future research should address adverse events, the cost-effectiveness of expanded panels, long-term remission outcomes and treatment efficacy across more precisely stratified disease severity levels to maximise clinical relevance.
CRD42024570014.
在重度抑郁症（MDD）中，与常规治疗（TAU）相比，药物基因组学（PGx）指导下的抗抑郁治疗效果如何？种族、疾病严重程度和基因检测范围如何影响治疗结果？
这项系统评价和荟萃分析纳入了13项随机对照试验（2013 - 2024年），比较了PGx指导治疗与MDD中的TAU治疗。截至2024年12月，检索了PubMed、Ovid Embase、Ovid Medline、Ovid PsycINFO和Cochrane图书馆。结局指标包括8周和12周时的缓解率和治愈率。亚组分析考察了种族和MDD严重程度。累积荟萃分析评估了基因检测范围。计算合并风险比（RRs）及其95%置信区间（CIs）以估计总体效应。
PGx指导治疗在8周（RR 1.23，95% CI 1.05至1.43）和12周（RR 1.29，95% CI 1.17至1.43）时显著提高了缓解率。8周时治愈率显著提高（RR 1.37，95% CI 1.
