TY - JOUR
T1 - Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia
T2 - A Systematic Review and Network Meta-analysis
AU - Tseng, Ping Tao
AU - Zeng, Bing Syuan
AU - Hung, Chao Ming
AU - Liang, Chih Sung
AU - Stubbs, Brendon
AU - Carvalho, Andre F.
AU - Brunoni, Andre R.
AU - Su, Kuan Pin
AU - Tu, Yu Kang
AU - Wu, Yi Cheng
AU - Chen, Tien Yu
AU - Li, Dian Jeng
AU - Lin, Pao Yen
AU - Hsu, Chih Wei
AU - Chen, Yen Wen
AU - Suen, Mein Woei
AU - Satogami, Kazumi
AU - Takahashi, Shun
AU - Wu, Ching Kuan
AU - Yang, Wei Cheng
AU - Shiue, Yow Ling
AU - Huang, Tiao Lai
AU - Li, Cheng Ta
N1 - Funding Information:
supported by a clinical lectureship jointly funded by Health Education England and the National Institute for Health Research (NIHR); is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust; and is supported by the Maudsley Charity, King’s College London, and the NIHR South London Collaboration for Leadership in Applied Health Research and Care funding. Dr Brunoni reported grants from São Paulo Research Foundation, Brazilian National Council of Scientific Development, and University of Sao Paulo Medical School; support from the Newton Advanced Fellowship; and in-kind support from Flow Neuroscience and MagVenture during the conduct of the study. Dr Su is supported by grants from An Nan Hospital, China Medical University, Tainan, Taiwan and China Medical University, Taichung, Taiwan. Dr Tu was supported by a grant from the Ministry of Science and Technology in Taiwan. Dr Lin is supported by grants from the Ministry of Science and Technology in Taiwan and Kaohsiung Chang Gung Memorial Hospital in Taiwan. Dr Hsu is supported by grants from the Ministry of Science and Technology in Taiwan. Dr Takahashi reported speaker’s honoraria from Teijin Pharma Ltd during the conduct of the study and from Dainippon Sumitomo Pharma, Eisai, Meiji Seika, Mochida Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/8
Y1 - 2022/8
N2 - Importance: Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear. Objective: To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms. Data Sources: The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021. Study Selection: A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model. Main Outcomes and Measures: The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms. Results: Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups. Conclusions and Relevance: In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted..
AB - Importance: Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear. Objective: To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms. Data Sources: The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021. Study Selection: A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model. Main Outcomes and Measures: The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms. Results: Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups. Conclusions and Relevance: In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted..
UR - http://www.scopus.com/inward/record.url?scp=85133491226&partnerID=8YFLogxK
U2 - 10.1001/jamapsychiatry.2022.1513
DO - 10.1001/jamapsychiatry.2022.1513
M3 - Review article
C2 - 35731533
AN - SCOPUS:85133491226
SN - 2168-622X
VL - 79
SP - 770
EP - 779
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 8
ER -
