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Mechanistic insights into taxane-induced psychiatric adverse events: a global pharmacovigilance and experimental investigation

Molecular Psychiatry volume 31, pages 1385–1397 (2026) Cite this article

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Abstract

Taxane drugs are essential chemotherapeutic agents in the clinical management of various solid tumors; however, their associated psychiatric adverse effects and underlying mechanisms remain insufficiently explored. This study aims to assess the association between taxane drugs and psychiatric adverse events (pAEs) and to investigate their potential biological mechanisms. The association between taxane drugs and pAEs was analyzed using the reporting odds ratio (ROR) method based on data from the Food and Drug Administration Adverse Event Reporting System (FAERS) (2013–2023) and the World Health Organization’s global pharmacovigilance database (Vigibase database). Tumor-bearing mouse models treated with taxane drugs were developed, and RNA sequencing was conducted to examine the underlying molecular mechanisms. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the activity of relevant pathways. A total of 10,132 cases and 10,525 cases of pAEs associated with taxane drugs were identified in the FAERS and Vigibase databases, respectively. Nine significant taxane-related psychiatric adverse events (TX-related pAEs) were identified, with emotional distress showing the strongest signal. Subgroup analysis indicated that women (RORFAERS = 15.244), individuals younger than 45 years (RORFAERS = 17.849), and breast cancer patients exhibited a higher risk. Mechanistic studies revealed four significantly associated signaling pathways: cobalamin metabolic process, regulation of response to oxidative stress, G protein-coupled receptor signaling, and nitric oxide-mediated signal transduction. This study is the first to systematically assess taxane drug-associated pAEs, elucidating the characteristics of high-risk populations and underlying molecular mechanisms, thereby offering valuable insights for clinical drug safety and personalized treatment.

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Fig. 1: Flowchart of the study analysis process.
The alternative text for this image may have been generated using AI.
Fig. 2: Temporal distribution characteristics of reports on TX-related pAEs (2013–2023).
The alternative text for this image may have been generated using AI.
Fig. 3: Psychiatric adverse events associated with taxane.
The alternative text for this image may have been generated using AI.
Fig. 4: Analysis of gender and age factors associated with TX-related pAEs.
The alternative text for this image may have been generated using AI.
Fig. 5: Tumor subgroup analysis of TX-related pAEs.
The alternative text for this image may have been generated using AI.
Fig. 6: Putative biological mechanisms and gene expression profiles associated with TX-related pAEs.
The alternative text for this image may have been generated using AI.

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Data availability

Raw data sets will be made available upon reasonable request to the corresponding author. All the data generated or analyzed during this study are included in this article. Adverse event records following chemotherapy are accessible through the FAERS Public Dashboard (https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard) and VigiBase from the Uppsala monitoring center (https://who-umc.org/vigibase/vigibase-services/). It should be noted that VigiBase, which serves as the WHO worldwide repository of documented potential adverse reactions to pharmaceutical products and is developed and maintained by the Uppsala Monitoring Centre, requires specific licensing agreements for access. It is important to highlight that information contained in VigiBase derives from multiple sources, and the likelihood of a suspected adverse reaction being associated with a particular medication can differ across individual cases. Furthermore, we acknowledge that this research does not reflect the viewpoints of the UMC or the World Health Organization.

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Acknowledgements

The workflow diagram was generated using the BioRender platform (https://BioRender.com).

Author information

Author notes

  1. These authors contributed equally: Anqi Lin, Yiyin Mai, Guichuan Lai, Zhengrui Li, Junyi Shen.

Authors and Affiliations

  1. Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China

    Anqi Lin, Yiyin Mai, Junyi Shen, Jian Zhang, Kailai Li & Peng Luo

  2. Donghai County People’s Hospital (Affiliated Kangda College of Nanjing Medical University), Lianyungang, 222000, China

    Anqi Lin & Peng Luo

  3. Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing, 401331, China

    Guichuan Lai

  4. Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, 200011, China

    Zhengrui Li

  5. Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Hank Z. H. Wong

  6. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

    Nan Zhang

  7. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China

    Quan Cheng

  8. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China

    Quan Cheng

  9. Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China

    Bicheng Ye

  10. Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200433, China

    Aimin Jiang

  11. Department of Gastrointestinal Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China

    Guiqing Jia

  12. Department of Cardiothoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China

    Qunqing Chen

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  1. Anqi Lin
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  2. Yiyin Mai
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  3. Guichuan Lai
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  7. Nan Zhang
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  9. Kailai Li
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  10. Quan Cheng
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  14. Guiqing Jia
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  15. Qunqing Chen
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Contributions

Writing-original draft, AQL, YYM, GCL, ZRL and JYS; Conceptualization, AMJ, PL, GQJ and QQC; Investigation, AQL, YYM, GCL, ZRL and JYS; Writing-review and editing, AQL, YYM, GCL, ZRL, JYS, HZHW, NZ, JZ, KLL, QC, BCY, AMJ, PL, GQJ and QQC; Visualization, AQL, YYM, GCL, ZRL. and JYS. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Aimin Jiang, Peng Luo, Guiqing Jia or Qunqing Chen.

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The authors declare no competing interests.

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a. All experiments were performed in keeping with the ARRIVE guidelines. b. The animal experimental protocol in this study was approved by the Experimental Animal Ethics Committee of Zhujiang Hospital, Southern Medical University (ID: LAEC-2023-222). c. The study does not include human participants. d. The study does not include data from humans.

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Lin, A., Mai, Y., Lai, G. et al. Mechanistic insights into taxane-induced psychiatric adverse events: a global pharmacovigilance and experimental investigation. Mol Psychiatry 31, 1385–1397 (2026). https://doi.org/10.1038/s41380-025-03252-1

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