{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:18:12Z","timestamp":1767896292388,"version":"3.49.0"},"reference-count":46,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,10,24]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Mental disorders affect nearly one billion people worldwide, posing major challenges to public health. While conventional treatments like psychotherapy and pharmacotherapy are effective for many patients, they are often associated with adverse effects and high non-response rates, underscoring the need for alternative approaches. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation, transcranial electric stimulation and transcranial focused ultrasound stimulation are increasingly used to treat psychiatric conditions. Although these methods show promising efficacy, data on their adverse effects remain fragmented and inconsistently reported. This meta-analysis aims to systematically compare the type and frequency of adverse effects, tolerability, and acceptability across different brain stimulation techniques and mental disorders. The findings will help improve safety monitoring and support more personalised, well-tolerated treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A systematic literature search of the Embase, MEDLINE(R), AMED (Allied and Complementary Medicine) and APA PsycINFO via OVID will be performed. Eligible studies include randomised controlled trials (RCTs) that compare active treatments or an active treatment with sham control, including both parallel group and cross-over studies, as well as prospective non-randomised studies such as case\u2013control studies and pre\u2013post studies investigating adverse effects of non-invasive brain stimulation in psychiatric populations. Included studies report on the frequency of adverse effects in a standardised manner. Primary outcomes comprise the incidence of specific adverse effects, dropout rates due to adverse effects (tolerability) and overall dropout rates (acceptability). Risk of bias will be assessed using the Cochrane RoB 2.0 tool for RCTs and the NHLBI quality assessment tool for pre\u2013post studies. The quality of case\u2013control studies will be assessed using the Newcastle-Ottawa scale. Provided that sufficient data are available and the network of comparisons is adequately connected, a network meta-analysis will be conducted to compare adverse effects and tolerability across interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>No ethical approval is needed to conduct this work. The findings will be submitted for publication in peer-reviewed journals and presented at scientific meetings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD420251164554<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-107577","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T13:40:30Z","timestamp":1767879630000},"page":"e107577","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Adverse effects of non-invasive brain stimulation as a treatment for mental disorders: protocol for a systematic review and meta-analysis"],"prefix":"10.1136","volume":"16","author":[{"given":"Celine","family":"Koelsch","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"},{"name":"Department of Psychiatry and Psychotherapy - School of Medicine & Health Sciences Carl von Ossietzky, University of Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Mirlach","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy - School of Medicine & Health Sciences Carl von Ossietzky, University of Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas Mehari","family":"Kinfe","sequence":"additional","affiliation":[{"name":"Mannheim Center for Neuromodulation and Neuroprosthetics (MCNN), Department of Neurosurgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"Mannheim Center for Translational Neuroscience (MCTN), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"Mannheim Comprehensive Medical Systems Technology Campus (MCSC), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Hurlemann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy - School of Medicine & Health Sciences Carl von Ossietzky, University of Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-1957","authenticated-orcid":false,"given":"Julian","family":"Mutz","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Selaskowski","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-2679","authenticated-orcid":false,"given":"Maximilian","family":"Kiebs","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"},{"name":"Department of Psychiatry and Psychotherapy - School of Medicine & Health Sciences Carl von Ossietzky, University of Oldenburg, Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"2026010805401700000_16.1.e107577.1","unstructured":"Organization WH . World mental health report: transforming mental health for all. World Health Organization; 2022."},{"key":"2026010805401700000_16.1.e107577.2","doi-asserted-by":"crossref","DOI":"10.1186\/s12888-025-06932-y","article-title":"Global burden of mental disorders in 204 countries and territories, 1990\u20132021: results from the global burden of disease study 2021","volume":"25","author":"Fan","year":"2025","journal-title":"BMC Psychiatry"},{"key":"2026010805401700000_16.1.e107577.3","doi-asserted-by":"publisher","DOI":"10.1002\/wps.21120"},{"key":"2026010805401700000_16.1.e107577.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01200-3"},{"key":"2026010805401700000_16.1.e107577.5","doi-asserted-by":"crossref","first-page":"110266","DOI":"10.1016\/j.pnpbp.2021.110266","article-title":"Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis","volume":"109","author":"Oliva","year":"2021","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2026010805401700000_16.1.e107577.6","doi-asserted-by":"crossref","DOI":"10.1186\/s12991-023-00480-z","article-title":"Discontinuation of antidepressant treatment: a retrospective cohort study on more than 20,000 participants","volume":"22","author":"Garcia-Marin","year":"2023","journal-title":"Ann Gen Psychiatry"},{"key":"2026010805401700000_16.1.e107577.7","first-page":"41","article-title":"Antidepressant adherence: are patients taking their medications?","volume":"9","author":"Sansone","year":"2012","journal-title":"Innov Clin Neurosci"},{"key":"2026010805401700000_16.1.e107577.8","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jad.2023.10.010","article-title":"Reasons for non-adherence with antidepressants using the Medication Adherence Reasons Scale in five European countries and United States","volume":"344","author":"Unni","year":"2024","journal-title":"J Affect Disord"},{"key":"2026010805401700000_16.1.e107577.9","doi-asserted-by":"crossref","DOI":"10.3390\/brainsci12070929","article-title":"Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation","volume":"12","author":"Kricheldorff","year":"2022","journal-title":"Brain Sci"},{"key":"2026010805401700000_16.1.e107577.10","doi-asserted-by":"crossref","first-page":"100066","DOI":"10.1016\/j.pmip.2020.100066","article-title":"Individualized theta-burst stimulation modulates hippocampal activity and connectivity in patients with major depressive disorder","volume":"23\u201324","author":"Mielacher","year":"2020","journal-title":"Personal Med Psychiatry"},{"key":"2026010805401700000_16.1.e107577.11","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2022.793253","article-title":"Transcranial Magnetic Stimulation in the Treatment of Neurological Diseases","volume":"13","author":"Somaa","year":"2022","journal-title":"Front Neurol"},{"key":"2026010805401700000_16.1.e107577.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2019.11.002"},{"key":"2026010805401700000_16.1.e107577.13","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.l1079","article-title":"Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis","volume":"364","author":"Mutz","year":"2019","journal-title":"BMJ"},{"key":"2026010805401700000_16.1.e107577.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.06.067"},{"key":"2026010805401700000_16.1.e107577.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2016.10.087"},{"key":"2026010805401700000_16.1.e107577.16","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyaa051"},{"key":"2026010805401700000_16.1.e107577.17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1177\/1073858420936167","article-title":"Transcranial Direct Current Stimulation and Cognition in Neuropsychiatric Disorders: Systematic Review of the Evidence and Future Directions","volume":"27","author":"Ciullo","year":"2021","journal-title":"Neuroscientist"},{"key":"2026010805401700000_16.1.e107577.18","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.4103\/1673-5374.335796","article-title":"Transcranial electrical stimulation in neurological disease","volume":"17","author":"Brown","year":"2022","journal-title":"Neural Regen Res"},{"key":"2026010805401700000_16.1.e107577.19","doi-asserted-by":"crossref","first-page":"105501","DOI":"10.1016\/j.neubiorev.2023.105501","article-title":"The effectiveness and safety of low-intensity transcranial ultrasound stimulation: A systematic review of human and animal studies","volume":"156","author":"Qin","year":"2024","journal-title":"Neurosci Biobehav Rev"},{"key":"2026010805401700000_16.1.e107577.20","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/ner.12946","article-title":"Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials","volume":"23","author":"Zis","year":"2020","journal-title":"Neuromodulation"},{"key":"2026010805401700000_16.1.e107577.21","doi-asserted-by":"crossref","first-page":"S555","DOI":"10.1016\/j.eurpsy.2016.01.2052","article-title":"Adverse effects in repetitive transcranial magnetic stimulation \u2013 prevention and management","volume":"33","author":"Sobreira","year":"2016","journal-title":"Eur psychiatr"},{"key":"2026010805401700000_16.1.e107577.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2012.07.024"},{"key":"2026010805401700000_16.1.e107577.23","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brs.2011.02.007","article-title":"Differences in the experience of active and sham transcranial direct current stimulation","volume":"5","author":"Kessler","year":"2012","journal-title":"Brain Stimul"},{"key":"2026010805401700000_16.1.e107577.24","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145710001690"},{"key":"2026010805401700000_16.1.e107577.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2007.01.004"},{"key":"2026010805401700000_16.1.e107577.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2022.05.015"},{"key":"2026010805401700000_16.1.e107577.27","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.brs.2022.05.002","article-title":"Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety","volume":"15","author":"Sarica","year":"2022","journal-title":"Brain Stimul"},{"key":"2026010805401700000_16.1.e107577.28","doi-asserted-by":"crossref","unstructured":"Arulpragasam AR , van \u2019t Wout-Frank M , Barredo J , et al . Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation\u2014A Paradigm Shift in Psychiatric Research. Front Psychiatry 2022;13. doi:10.3389\/fpsyt.2022.825802","DOI":"10.3389\/fpsyt.2022.825802"},{"key":"2026010805401700000_16.1.e107577.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62265-8"},{"key":"2026010805401700000_16.1.e107577.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2020.10.003"},{"key":"2026010805401700000_16.1.e107577.31","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.brs.2017.10.020","article-title":"Safety of repeated sessions of transcranial direct current stimulation: A systematic review","volume":"11","author":"Nikolin","year":"2018","journal-title":"Brain Stimul"},{"key":"2026010805401700000_16.1.e107577.32","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jpsychires.2024.05.035","article-title":"Adverse event monitoring and reporting in pediatric neuromodulatory studies: A systematic review","volume":"175","author":"Lodewyk","year":"2024","journal-title":"J Psychiatr Res"},{"key":"2026010805401700000_16.1.e107577.33","doi-asserted-by":"publisher","DOI":"10.1097\/WNP.0b013e318205135f"},{"key":"2026010805401700000_16.1.e107577.34","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2026010805401700000_16.1.e107577.35","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2385"},{"key":"2026010805401700000_16.1.e107577.36","doi-asserted-by":"publisher","DOI":"10.1590\/S0104-11692007000300023"},{"key":"2026010805401700000_16.1.e107577.37","doi-asserted-by":"crossref","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan-a web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst Rev"},{"key":"2026010805401700000_16.1.e107577.38","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD201601"},{"key":"2026010805401700000_16.1.e107577.39","unstructured":"Study quality assessment tools | NHLBI, NIH. Available: https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools [Accessed 2 May 2025]."},{"key":"2026010805401700000_16.1.e107577.40","unstructured":"Ottawa Hospital Research Institute . Available: https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp [Accessed 2 May 2025]."},{"key":"2026010805401700000_16.1.e107577.41","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39500.677199.AE"},{"key":"2026010805401700000_16.1.e107577.42","doi-asserted-by":"publisher","DOI":"10.1186\/2046-4053-4-1"},{"key":"2026010805401700000_16.1.e107577.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.02.012"},{"key":"2026010805401700000_16.1.e107577.44","doi-asserted-by":"crossref","unstructured":"Viechtbauer W . Conducting Meta-Analyses in R with the metafor Package. J Stat Soft 2010;36. doi:10.18637\/jss.v036.i03","DOI":"10.18637\/jss.v036.i03"},{"key":"2026010805401700000_16.1.e107577.45","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v106.i02"},{"key":"2026010805401700000_16.1.e107577.46","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-023796","article-title":"Cognitive effects of non-surgical brain stimulation for major depressive disorder: protocol for a systematic review and meta-analysis","volume":"9","author":"Kiebs","year":"2019","journal-title":"BMJ Open"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-107577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T13:40:39Z","timestamp":1767879639000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-107577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,8]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/bmjopen-2025-107577"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-107577","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}