{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:38:33Z","timestamp":1792363113564,"version":"4.4.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Transcranial pulse stimulation is a novel noninvasive brain stimulation technique with preliminary evidence of antidepressant effects; however, its efficacy has not been tested in a double-blind, sham-controlled randomized clinical trial.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine the antidepressant efficacy of transcranial pulse stimulation for major depressive disorder.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This 2-arm, parallel-design, double-blind, sham-controlled randomized clinical trial was conducted between June 1, 2023, and October 31, 2025, at the Hong Kong Polytechnic University. Patients with major depressive disorder and a Hamilton Depression Rating Scale score of 14 or higher were convenience sampled and enrolled.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized 1:1 to receive 12 sessions (1000 pulses per session) of active or sham transcranial pulse stimulation targeting the left dorsolateral prefrontal cortex during 4 weeks.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Change in Montgomery-\u00c5sberg Depression Rating Scale score (range, 0 [no depression] to 60 [severe depression], with a change of at least 6 indicating minimal change and 12 or more indicating substantial change) after 12 treatment sessions.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This modified intention-to-treat analysis included 80 participants (mean [SD] age, 35.6 [11.7] years; mean [SD] years of education, 15.5 [3.3]; 53 females), with 74 completing treatment and 6 withdrawing (2 from sham due to adverse effects); 40 participants were randomized to the active group and 40 to the sham group. The active group demonstrated a statistically significantly greater reduction in Montgomery-\u00c5sberg Depression Rating Scale scores than the sham group (mean difference, \u22124.19; 95% CI, \u22128.33 to \u22120.04;\n P<\/jats:italic>\n \u2009=\u2009.048; Hedges\n g<\/jats:italic>\n \u2009=\u20090.45). Resting-state functional magnetic resonance imaging analyses found that, compared with the sham stimulation, active stimulation significantly enhanced functional connectivity within the left dorsolateral prefrontal cortex (mean difference, 0.11; 95% CI, 0.03-0.19;\n P<\/jats:italic>\n = .009); between the left dorsolateral prefrontal cortex and left orbitofrontal, superior medial prefrontal, and pregenual anterior cingulate cortices (mean difference, 0.11; 95% CI, 0.05-0.17;\n P<\/jats:italic>\n &amp;lt; .001); and between the left dorsolateral prefrontal cortex and posterior cingulate cortex and bilateral precuneus and calcarine cortex (mean difference, 0.08; 95% CI, 0.01-0.16;\n P<\/jats:italic>\n = .02).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this randomized clinical trial of transcranial pulse stimulation, the treatment was safe, well tolerated, and associated with antidepressant effects and modulation of multiple depression-relevant brain circuits. These findings provide a rationale for future studies to optimize therapeutic efficacy by increasing the number of treatment sessions and refining targeting strategies.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05551585<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.21592","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:07:06Z","timestamp":1783350426000},"page":"e2621592","source":"Crossref","is-referenced-by-count":1,"title":["Prefrontal Transcranial Pulse Stimulation for Major Depressive Disorder"],"prefix":"10.1001","volume":"9","author":[{"given":"Penny Ping","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Beisteiner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Padberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universit\u00e4t Hospital, Ludwig-Maximilians-Universit\u00e4t Munich, Munich, Germany"},{"name":"DZPG (German Center for Mental Health), Partner Site Munich-Augsburg, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg S.","family":"Kranz","sequence":"additional","affiliation":[{"name":"Department of 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