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Painful physical symptoms and antidepressant treatment outcome in depression: a systematic review and meta-analysis

Molecular Psychiatry (2024)Cite this article

Subjects

Abstract

Background

Painful physical symptoms (PPS) are highly prevalent in patients with major depressive disorder (MDD). Presence of PPS in depressed patients are potentially associated with poorer antidepressant treatment outcome. We aimed to evaluate the association of baseline pain levels and antidepressant treatment outcomes.

Methods

We searched PubMed, Embase and Cochrane Library databases from inception through February 2023 based on a pre-registered protocol (PROSPERO: CRD42022381349). We included original studies that reported pretreatment pain measures in antidepressant treatment responder/remitter and non-responder/non-remitter among patients with MDD. Data extraction and quality assessment were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses by two reviewers independently. The primary outcome was the difference of the pretreatment pain levels between antidepressant treatment responder/remitter and non-responder/non-remitter. Random-effects meta-analysis was used to calculate effect sizes (Hedge’s g) and subgroup and meta-regression analyses were used to explore sources of heterogeneity.

Results

A total of 20 studies were included. Six studies reported significantly higher baseline pain severity levels in MDD treatment non-responders (Hedge’s g = 0.32; 95% CI, 0.13–0.51; P = 0.0008). Six studies reported the presence of PPS (measured using a pain severity scale) was significantly associated with poor treatment response (OR = 1.46; 95% CI, 1.04-2.04; P = 0.028). Five studies reported significant higher baseline pain interference levels in non-responders (Hedge’s g = 0.46; 95% CI, 0.32–0.61; P < 0.0001). Four studies found significantly higher baseline pain severity levels in non-remitters (Hedge’s g = 0.27; 95% CI, 0.14–0.40; P < 0.0001). Eight studies reported the presence of PPS significantly associated with treatment non-remission (OR = 1.70; 95% CI, 1.24–2.32; P = 0.0009).

Conclusions

This study suggests that PPS are negatively associated with the antidepressant treatment outcome in patients with MDD. It is possible that better management in pain conditions when treating depression can benefit the therapeutic effects of antidepressant medication in depressed patients.

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Fig. 1
Fig. 2: Random-effects model meta-analysis for baseline pain severity levels and antidepressant treatment response.
Fig. 3: Random-effects model meta-analysis for painful physical symptoms and antidepressant treatment response.
Fig. 4: Random-effects model meta-analysis for baseline pain interference levels and antidepressant treatment response.

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Data availability

Study data are available on request to the corresponding author at yabin.wei@bjmu.edu.cn.

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Acknowledgements

JJL and YBW are supported by National Natural Science Foundation of China (JJL, 82171530; YBW, 82001430). PD is supported by the Ministry of Science and Technology of China (STI2030-Major Projects 2021ZD0202105).

Funding

The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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Author notes

  1. These authors contributed equally: Jia Jia Liu, Xiao Huang.

Authors and Affiliations

  1. School of Nursing, Peking University, Beijing, China

    Jia Jia Liu

  2. Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, China

    Xiao Huang

  3. School of Public Health, National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China

    Yan-Ping Bao

  4. Peking University Sixth Hospital, Peking University Institute of Mental Health, Key of Mental Health, Ministry of Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China

    Lin Lu

  5. Peking-Tsinghua Center for Life Sciences and International Data Group/McGovern Institute for Brain Research, National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China

    Lin Lu

  6. Psychiatric Department, Peking University Sixth Hospital, Beijing, China

    Ping Dong

  7. Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA

    Owen M. Wolkowitz

  8. Department of Psychiatry and Center for Circadian Biology, University of California San Diego (UCSD), La Jolla, CA, USA

    John R. Kelsoe

  9. National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China

    Jie Shi & Ya Bin Wei

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Contributions

JJL, YBW, PD and JS conceptualized and initiated the study. JJL, XH and YPB screened the text. JJL and XH analyzed the data. JJL and YBW created the forest plots. JJL, LL, and XH wrote the first draft of the manuscript with input from YBW and JS. YBW and YPB proofread the manuscript. JJL, YBW, PD, OMW and JRK revised the manuscript. All authors contributed to the design of the study and the final manuscript. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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Correspondence to Jie Shi or Ya Bin Wei.

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Liu, J.J., Huang, X., Bao, YP. et al. Painful physical symptoms and antidepressant treatment outcome in depression: a systematic review and meta-analysis. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02496-7

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