{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:44:10Z","timestamp":1791639850848,"version":"4.3.4"},"reference-count":65,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Transcranial direct current stimulation (tDCS) shows promise for treating depression. The precision and focality of stimulation may influence therapeutic outcomes; thus, investigation of personalized focal high-definition (HD) tDCS for treating depression is needed.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine whether HD-tDCS therapy can improve mood in patients with moderate to severe depression.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This randomized clinical trial used a double-blind, sham-controlled, parallel study design. The trial was conducted from December 1, 2020, to March 7, 2024, at UCLA. Each participant received a 4-week follow-up. Participants were required to meet diagnostic criteria for a current major depressive episode (evaluated using the Mini International Neuropsychiatric Interview), present moderate to severe depressive symptoms (ie, have a 17-item Hamilton Depression Rating Scale [HAMD] score \u226514 and &amp;lt;24), be either treatment naive or receiving a stable standard antidepressant regimen, and be 18 to 65 years of age. Key exclusion criteria included treatment-resistant depression, bipolar disorder, or schizophrenia. Of 560 volunteers screened, 71 were found to be eligible for participation.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants received 20 minutes of active or sham HD-tDCS each day for 12 consecutive working days. Structural magnetic resonance imaging and frameless stereotaxic neuronavigation were used to personalize the HD-tDCS configuration to each participant.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Pretreatment to posttreatment change in the HAMD score.<\/jats:p><\/jats:sec>Results<\/jats:title>Seventy-one participants (44 female [62.0%]; mean [SD] age, 34.3 [10.4] years) were randomized to receive active (n\u2009=\u200940) or sham (n\u2009=\u200931) HD-tDCS therapy. The primary outcome measure, mean (SD) pretreatment to posttreatment change in HAMD score, differed significantly between treatment groups (group difference, \u22122.2 [4.3]; P<\/jats:italic>\u2009=\u2009.04; Cohen d<\/jats:italic>, \u22120.50 [95% CI, \u22120.99 to \u22120.01]). Post hoc 2-sample t<\/jats:italic> tests revealed significant decreases in HAMD scores within both groups, with (significantly) greater decreases in the active treatment group (active HD-tDCS group, \u22127.8 [4.2]; sham HD-tDCS group, \u22125.6 [4.4]). HD-tDCS was well-tolerated, with mild to no adverse effects. Exploratory analyses indicated a significant active treatment-related improvement in the anxiety dimension of the primary outcome measure (group difference, \u22120.68 [1.42]; P<\/jats:italic>\u2009=\u2009.049; Cohen d<\/jats:italic>, \u22120.48 [95% CI, \u22120.96 to \u22120.004]).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial of HD-tDCS in participants with moderate to severe depression, the 12-day HD-tDCS therapy was observed to significantly improve mood with a moderate effect size. Similar effect sizes in pharmacotherapy, psychotherapy, and conventional tDCS\u2013based therapy have been observed to occur substantially later, highlighting the clinical potential of more precise and focal tDCS in depression. Follow-up studies with appropriate maintenance treatments are needed to clarify the persistence of antidepressant effects, as well as possible therapy optimizations. Exploratory analyses indicated that HD-tDCS therapy also may be salient for treating anxiety disorders.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04507243<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.31189","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:00:31Z","timestamp":1757602831000},"page":"e2531189","source":"Crossref","is-referenced-by-count":13,"title":["Personalized High-Definition Transcranial Direct Current Stimulation for the Treatment of Depression"],"prefix":"10.1001","volume":"8","author":[{"given":"Mayank A.","family":"Jog","sequence":"first","affiliation":[{"name":"Department of Neurology, UCLA, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biobehavioral Sciences, UCLA, Los 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