{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:22:10Z","timestamp":1793848930966,"version":"4.6.1"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Depression relapse poses significant medical and economic challenges. Repetitive transcranial magnetic stimulation (rTMS) as maintenance treatment may prevent relapse of treatment-resistant depression (TRD).<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare the effectiveness between low-frequency rTMS and lithium in preventing TRD relapse.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This randomized clinical trial was conducted from September 1, 2018, to May 31, 2023, at Keio University Hospital and Shinjuku-Yoyogi Mental Lab Clinic, Tokyo, Japan, among 75 participants with TRD aged 18 years or older with moderate-to-severe depressive symptoms despite at least 2 adequate antidepressant treatments who subsequently responded to an acute course of bilateral rTMS.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were randomly assigned at a 1:1 ratio to receive right dorsolateral prefrontal 1-Hz rTMS (24 weekly sessions; 120% of the resting motor threshold, 900 pulses in 15 minutes) or 24-week maintenance treatment with lithium pharmacotherapy. Participants were maintained on the same venlafaxine dose (150-225 mg\/d) as the acute-phase dose.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was the between-group difference in baseline-adjusted Montgomery-\u00c5sberg Depression Rating Scale (MADRS) scores (range, 0-60, where 0 indicates no symptoms and 60 indicates most severe symptoms) at week 24, which was analyzed using a linear mixed-effects model for repeated measures in an intention-to-treat sample. The secondary outcome was the time to relapse (defined as a MADRS score \u226522), which was analyzed using Kaplan-Meier survival curves. Adverse events were also compared between groups.<\/jats:p><\/jats:sec>Results<\/jats:title>Among the 75 participants, 38 were assigned to the rTMS group (mean [SD] age, 44.1 [11.7] years; 21 male participants [55.3%]; baseline mean [SD] MADRS score, 8.9 [4.7]), and 37 were assigned to the lithium group (mean [SD] age, 44.1 [11.1] years; 19 male participants [51.4%]; baseline mean [SD] MADRS score, 7.9 [4.5]). There was no significant between-group difference in the primary outcome at week 24 (0.3 points [95% CI, \u22122.7 to 3.3 points]; P<\/jats:italic>\u2009=\u2009.84). Survival analysis showed no meaningful between-group difference in relapse rates. During the 24-week maintenance phase, there were 7 patients who relapsed in each group. There was a higher number of adverse events among participants in the lithium group (n\u2009=\u200916) than in the rTMS group (n\u2009=\u20093; odds ratio, 7.10 [95% CI, 1.84-27.49]; P<\/jats:italic>\u2009=\u2009.005).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial, low-frequency rTMS of the right prefrontal cortex as maintenance treatment showed comparable efficacy, as well as better safety and tolerance, compared with lithium. Maintenance low-frequency rTMS could be a promising relapse prevention strategy for patients with TRD.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>Japan Registry of Clinical Trials: jRCTs032180188<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.15881","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T15:31:04Z","timestamp":1750087864000},"page":"e2515881","source":"Crossref","is-referenced-by-count":18,"title":["Repetitive Transcranial Magnetic Stimulation as Maintenance Treatment of Depression"],"prefix":"10.1001","volume":"8","author":[{"given":"Yoshihiro","family":"Noda","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"},{"name":"Department of Psychiatry, International University of Health and Welfare, Mita Hospital, Mita, Minato-ku, Tokyo, Japan"},{"name":"Shinjuku-Yoyogi Mental Lab Clinic, Sendagaya, Shibuya-ku, Tokyo, 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