Li CC, Zhou Y, Chen KX, Zhang L, Gu WL, Gu H. Meta-analysis of dopaminergic-serotonergic modulation strategies for depressive symptoms in Parkinson’s disease. World J Psychiatry 2026; 16(5): 115867 [DOI: 10.5498/wjp.v16.i5.115867]
Corresponding Author of This Article
Hong Gu, Associate Chief Pharmacist, Department of Pharmacy, Jingjiang People’s Hospital Affiliated to Yangzhou University, No. 28 Zhongzhou Road, Taizhou 214500, Jiangsu Province, China. honggujj@163.com
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Psychiatry
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Meta-Analysis
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May 19, 2026 (publication date) through May 5, 2026
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World Journal of Psychiatry
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2220-3206
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Li CC, Zhou Y, Chen KX, Zhang L, Gu WL, Gu H. Meta-analysis of dopaminergic-serotonergic modulation strategies for depressive symptoms in Parkinson’s disease. World J Psychiatry 2026; 16(5): 115867 [DOI: 10.5498/wjp.v16.i5.115867]
World J Psychiatry. May 19, 2026; 16(5): 115867 Published online May 19, 2026. doi: 10.5498/wjp.v16.i5.115867
Meta-analysis of dopaminergic-serotonergic modulation strategies for depressive symptoms in Parkinson’s disease
Cheng-Cheng Li, Yan Zhou, Kai-Xia Chen, Li Zhang, Wen-Lie Gu, Hong Gu
Cheng-Cheng Li, Yan Zhou, Li Zhang, Wen-Lie Gu, Hong Gu, Department of Pharmacy, Jingjiang People’s Hospital Affiliated to Yangzhou University, Taizhou 214500, Jiangsu Province, China
Cheng-Cheng Li, Kai-Xia Chen, Clinical Trial Agency Office, Jingjiang People’s Hospital Affiliated to Yangzhou University, Taizhou 214500, Jiangsu Province, China
Co-first authors: Cheng-Cheng Li and Yan Zhou.
Co-corresponding authors: Kai-Xia Chen and Hong Gu.
Author contributions: Li CC and Zhou Y are co-first authors of this manuscript, they contributed equally and jointly participate in research design, data collection, and organization. They collaborate to complete statistical analysis and write and revise the initial draft of the paper. They are responsible for the core content of the research and the authenticity of the data. Chen KX and Gu H are co-corresponding authors of this manuscript. Chen KX and Gu H jointly coordinate the overall research process, review the research plan and data analysis results, and deeply revise the final draft of the paper; Chen KX is responsible for evaluating the quality of literature and controlling academic viewpoints; Gu H is responsible for coordinating submissions, responding to review comments, and academic communication after publication. Zhang L assisted in data validation and chart creation; Gu WL participated in literature search, organization, and manuscript proofreading, providing support for research implementation and manuscript improvement. All authors have read and agreed to the final published version of the paper, confirming that the research process complies with academic ethical standards and has no conflicts of interest.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Hong Gu, Associate Chief Pharmacist, Department of Pharmacy, Jingjiang People’s Hospital Affiliated to Yangzhou University, No. 28 Zhongzhou Road, Taizhou 214500, Jiangsu Province, China. honggujj@163.com
Received: November 14, 2025 Revised: December 16, 2025 Accepted: February 3, 2026 Published online: May 19, 2026 Processing time: 166 Days and 1.1 Hours
Abstract
BACKGROUND
Depressive disorder is a common non-motor complication of Parkinson’s disease (PD) that seriously impairs the quality of life. Evidence suggests that dopaminergic and serotonergic dysfunctions jointly contribute to this condition. However, the therapeutic value of dopaminergic-serotonergic modulation strategies remain unclear.
AIM
To evaluate the efficacy and safety of dopaminergic and/or selective serotonin reuptake inhibitor (SSRI) therapy in patients with PD and depression.
METHODS
English-language randomized controlled trials published between January 2000 and January 2025 were retrieved from the PubMed and EMBASE databases. Eligible studies compared dopaminergic agents, SSRIs, or their combination with placebo or active monotherapy. The primary outcomes included improvement in depressive symptoms, with secondary outcomes of motor function, quality of life, and safety. Meta-analysis was performed using Stata/RevMan software to assess pooled effects, heterogeneity, and publication bias.
RESULTS
Five randomized controlled trials comprising 508 patients met the inclusion criteria. Dopaminergic-serotonergic modulation significantly improved depressive symptoms compared with control therapy [risk ratio = 1.35, 95% confidence interval (CI): 1.15-1.60] and enhanced quality of life (mean difference = -2.41, 95%CI: -3.02 to -1.79). Although a statistically significant improvement in motor scores was observed in the initial pooled analysis, sensitivity analysis revealed that this result was driven by a single high-risk study, and the effect became non-significant after its exclusion (mean difference = -0.75, 95%CI: -0.91 to -0.59). The risk of treatment discontinuation due to adverse events was slightly higher, but not statistically significant (risk ratio = 1.61, 95%CI: 0.82-3.19). The results remained stable after sensitivity and Bayesian analyses.
CONCLUSION
Therapeutic strategies targeting dopaminergic and serotonergic pathways through dopaminergic agents, SSRIs, or their combination can improve depressive symptoms and quality of life in patients with PD and depressive disorder, while showing no added benefit for motor function. These treatments appear safe and well-tolerated, suggesting dopaminergic-serotonergic modulation may represent a valuable strategy for managing depression in PD.
Core Tip: This meta-analysis of five studies discussed the clinical efficacy of dopaminergic agents combined with selective serotonin reuptake inhibitors in the treatment of Parkinson’s disease with depressive disorder. The results showed that the effective rate of depression improvement and the quality of life score of the combined treatment were higher, but there was no significant difference in motor function. These findings highlight the importance of combined therapy for Parkinson’s disease and depressive disorders.
