The Efficacy and Safety of Continuous Theta Burst Stimulation for Auditory Hallucinations: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials
Afshan Mumtaz1, Akuti Khanna2, ZEESHAN SHERIFF3, Harshith Venkata Sai Dova4, Abhinaya Shrangare5, Melanie Francis6, Soura Rajeshwara7, Ansu Paloh8, Mikhail Burke9, PRAGYA MAHARJAN10, Kush Raval11, Abiheshan Thiruchelvam12, Khooshi Patel13, Pranati Gudipati14, Amarachi Ejindu15, Ali Salman16
1AINeuroCare, 2JSS Medical College, 3An-Noor Eye Hospital, 4Central and North West London NHS Foundation Trust, 5Bhukara State Medical University, 6St. Johns Medical College, 7Shimoga Institute of Medical Sciences, 8Tomo Riba Institute of Health and Medical Sciences, 9Bellevue Hospital, 10KIRTIPUR HOSPITAL (Proposed PUSHPALAL MEDICAL COLLEGE AND TEACHING HOSPITAL), 11GCS Medical College, Hospital and Research Centre, 12District General Hospital Ampara, Sri Lanka, 13Surat Municipal Institute of Medical Education and Research, 14JNMC, KLE University Belgaum, 15Abia State University Teaching Hospital, 16Department of Medicine, Dow University of Health Sciences
Objective:
To assess the efficacy and safety of continuous theta burst stimulation (cTBS) for auditory hallucinations in schizophrenia patients through an updated systematic review and meta-analysis of randomized controlled trials (RCTs).
Background:
Auditory hallucinations persist in a significant proportion of patients with schizophrenia-spectrum disorders despite optimal antipsychotic treatment. cTBS is a form of transcranial magnetic stimulation that is investigated as a potential intervention in several neuropsychiatric conditions, including schizophrenia spectrum disorders.
Design/Methods:
We updated the meta‑analysis of Ye et al. (August 2024) by retaining all eligible studies included by Ye et al. and extending the search to cover till August 2025. The same databases were searched (PubMed, EMBASE, Web of Science, and the Cochrane Library) using identical keywords and Boolean operators to ensure methodological consistency as was in the original review.
Results:
Analysis of the 5 RCTs chosen (n = 291) demonstrated that active cTBS significantly reduced auditory hallucination severity compared to sham controls assessed from PSYRAT- AH score [WMD = –2.88, 95% CI: –4.91 to –0.84; P = 0.006]. Significant improvement in primary outcome was observed with >10 stimulation sessions and >9000 total pulses [WMD = –3.51, 95% CI: –6.04 to –0.98; P = 0.007], and when cTBS was applied to bilateral temporo-parietal cortex [WMD = –2.10, 95% CI: –3.57 to –0.63; P = 0.005]. Active cTBS also improved PANSS positive scores [WMD = –1.76, 95% CI: –3.31 to –0.21; P = 0.03], though no significant effects were noted for PANSS negative scores or the P3 (hallucinatory behavior) item. Adverse events such as headache or local pain did not differ significantly between both the groups.
Conclusions:
Active cTBS is a safe and effective adjunctive intervention for reducing auditory hallucinations in schizophrenia, particularly with higher treatment intensity and bilateral temporo-parietal stimulation.
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