The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials

Shi-Yi Ye; Chun-Nuan Chen; Bo Wei; Jin-Qiong Zhan; Yi-Heng Li; Chen Zhang; Jing-Jing Huang; Yuan-Jian Yang

doi:10.3389/fpsyt.2024.1446849

The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials

Front Psychiatry. 2024 Aug 19:15:1446849. doi: 10.3389/fpsyt.2024.1446849. eCollection 2024.

Authors

Shi-Yi Ye^#^{1

2}, Chun-Nuan Chen^#³, Bo Wei^#^{1

4}, Jin-Qiong Zhan^{1

4}, Yi-Heng Li^{1

4}, Chen Zhang⁵, Jing-Jing Huang⁶, Yuan-Jian Yang^{1

4}

Affiliations

¹ Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
² The 3rd Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, China.
³ Department of Neurology, The Second Clinical Medical College, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
⁴ Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, China.
⁵ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China.

^# Contributed equally.

Abstract

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia.

Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data.

Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I² = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I² = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group.

Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Keywords: auditory hallucinations; continuous theta burst stimulation (cTBS); meta-analysis; non-invasive brain stimulation; treatment.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by grants from the National Natural Science Foundation of China (82271557, 82060258) and the Jiangxi Provincial Clinical Research Center Projects (2020BCG74002). It was also supported by the Natural Science Foundation of Fujian Province (2023J01104), the Joint Funds for the Innovation of Science and Technology of Fujian Province (2023Y9255) and the Science and Technology Bureau of Quanzhou (2023C005YR).