For the millions of adults with major depressive disorder who achieve inadequate relief from medication, non-invasive brain stimulation has quietly been gaining clinical ground. A rigorous sham-controlled trial now adds meaningful evidence that a streamlined, once-daily protocol can deliver measurable antidepressant effects — a finding relevant to the design of accessible outpatient neuromodulation services.
This randomized clinical trial enrolled 73 adults aged 22–65 with MDD and clinically significant depression (Montgomery-Åsberg Depression Rating Scale scores ≥20) at a North Norwegian outpatient psychiatric clinic between 2022 and 2025. Participants received 10 weekday sessions of either active intermittent theta-burst stimulation (iTBS) — 600 magnetic pulses delivered at 120% of resting motor threshold to the left dorsolateral prefrontal cortex — or sham stimulation using a validated placebo coil. Between-group differences in both clinician-rated MADRS scores and self-reported Beck Depression Inventory-II scores were assessed at day 10, with a four-week follow-up to examine durability of response.
The trial addresses a specific evidence gap: while iTBS has regulatory approval and established efficacy in accelerated multi-session formats, controlled evidence for simpler once-daily regimens was thin. That gap matters clinically, because once-daily scheduling dramatically reduces patient burden and logistical complexity compared to protocols requiring multiple sessions per day.
Placing this in context, iTBS received FDA clearance in 2018 partly on the basis of non-inferiority to conventional repetitive TMS. The broader literature supports left DLPFC stimulation as a reproducible antidepressant target, but effect sizes vary considerably across studies and populations. With only 73 participants, this trial is underpowered to detect moderators — meaning it cannot yet tell us who benefits most. The single-site, Northern European sample also limits generalizability. Nevertheless, as a sham-controlled design with blinded clinician ratings and a four-week durability window, it represents a methodologically credible incremental addition — one that could help standardize once-daily iTBS as a practical clinical option.