JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Efficacy of non-invasive brain stimulation combined with medications for bipolar depression: a systematic review and meta-analysis of randomized controlled trials

Author(s): Shuangyu QI^{1^}, Qianfeng CHEN^{1^}, Yuanyuan ZENG⁸, Saboor SAEED^1, ², Xiaonan GUO¹, Hetong ZHOU¹, Shaohua HU^1, ^2, ^3, ^4, ^5, ^6, ⁷
Affiliation(s): ¹Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China ²Nanhu Brain-computer Interface institute, Hangzhou 311100, China ³The Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou 310003, China ⁴MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou 310003, China ⁵Brain Research Institute of Zhejiang University, Hangzhou 310003, China ⁶The State Key Lab of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310003 China ⁷Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou 310003, China ⁸Hangzhou Medical College, Hangzhou 310003, China
Corresponding email(s): Shaohua HU, dorhushaohua@zju.edu.cn Hetong ZHOU, 1168600035@zju.edu.cn
Key Words: Bipolar disorder; Transcranial magnetic stimulation; Transcranial direct current stimulation

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Shuangyu QI^{1^*}, Qianfeng CHEN^{1^*}, Yuanyuan ZENG⁸, Saboor SAEED^1,², Xiaonan GUO¹, Hetong ZHOU¹, Shaohua HU^1,^2,^3,^4,^5,^6,⁷. Efficacy of non-invasive brain stimulation combined with medications for bipolar depression: a systematic review and meta-analysis of randomized controlled trials[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500421

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author="Shuangyu QI^{1^*}, Qianfeng CHEN^{1^*}, Yuanyuan ZENG⁸, Saboor SAEED^1,², Xiaonan GUO¹, Hetong ZHOU¹, Shaohua HU^1,^2,^3,^4,^5,^6,⁷",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2500421"
}

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Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Bipolar disorder is a chronic psychiatric disorder with severe disease burden, especially as induced by bipolar depression. Noninvasive brain stimulation (NIBS) has shown antidepressant potential, but its adjunctive benefit when combined with pharmacotherapy remains unclear. This meta-analysis evaluates the efficacy of NIBS combined with medication. Methods: A comprehensive search was conducted across PubMed, Embase, and the Web of Science, including studies up to July 31, 2024. Randomized controlled trials comparing NIBS plus medication with medication monotherapy or sham stimulation were included. The primary outcome evaluated was the change in depressive symptoms; secondary outcomes included response rate, remission rate, dropout rate, and cognitive changes. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. Results: Seventeen randomized controlled trials (RCTs) involving 748 screened records were included, comprising 11 transcranial magnetic stimulation (TMS) trials and six transcranial direct current stimulation (tDCS) trials. Compared with pharmacotherapy alone, NIBS combined with medication was linked to greater reductions in depressive symptoms (SMD=?0.69). Both TMS and tDCS were associated with improvements in depressive symptoms and response rates, whereas a statistically significant association with remission was observed only for TMS. No significant differences were observed in dropout rates or cognitive outcomes. Meta-regression analyses did not identify consistent associations between treatment effects and demographic or stimulation-related variables, although an exploratory potential association between tDCS current intensity and symptom improvement was observed. Conclusions: NIBS combined with medication may offer additional benefit over pharmacotherapy alone for bipolar depression. Nevertheless, substantial heterogeneity and the limited number of available trials warrant cautious interpretation. Further well-designed randomized controlled trials are needed to confirm these findings and to clarify the role of stimulation parameters.

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