The ONE-D Study — One-Day Theta Burst Stimulation for Treatment-Resistant Depression (Vaughn et al., 2025)
The ONE-D Study — One-Day Theta Burst Stimulation for Treatment-Resistant Depression (Vaughn et al., 2025)
What this study was
Who was studied
What the protocol involved
What the results showed
What it means — and what it doesn't
Why this study matters for patients
What this study was
The ONE-D study is the first published clinical trial evaluating a complete course of accelerated iTBS delivered in a single day, augmented with D-cycloserine to enhance neuroplasticity throughout treatment. It was conducted at the University of Toronto and affiliated sites under the direction of researchers including Dr. Jonathan Downar, one of the leading figures in accelerated TMS research. The study was published in the Transcranial Magnetic Stimulation Journal in 2025.
Who was studied
The trial enrolled 32 patients with treatment-resistant major depressive disorder patients who had failed to respond adequately to prior antidepressant treatment. All 32 patients completed the full one-day protocol. No patients dropped out due to adverse events, and no serious adverse events were reported across the entire trial.
What the protocol involved
The ONE-D protocol delivered 20 iTBS sessions in a single day, spaced approximately 30 minutes apart, for a total treatment duration of approximately 9.5 hours. Each session consisted of 1,800 pulses. Before each session, patients received an oral dose of D-cycloserine a partial NMDA receptor agonist that primes the brain's neuroplasticity mechanisms, making neurons more responsive to the activity-driven changes TMS is trying to induce. The stimulation target was the left dorsolateral prefrontal cortex using standard scalp-based targeting.
What the results showed
87.5% response rate at six weeks, measured by the Hamilton Depression Rating Scale (HDRS-17) 71.9% remission rate at six weeks 84.4% response rate at 12 weeks 50% sustained remission at six months Response followed a delayed, exponential trajectory peaking at weeks four to six following treatment, consistent with the biology of neuroplasticity consolidation rather than an immediate pharmacological effect Mean discomfort during treatment was rated 5.8 out of 10 present but well-tolerated across the full day
What it means and what it doesn't
The ONE-D study is a small open-label trial 32 patients, no sham control group. Without a sham comparison arm, the results cannot definitively isolate how much of the effect was treatment-specific versus expectation or natural recovery. The absence of a sham arm is the study's primary methodological limitation and is acknowledged by the authors.
That said, the response and remission rates achieved in a treatment-resistant population are among the highest published for any TMS protocol. The six-month durability data is particularly notable: 50% sustained remission at six months in a treatment-resistant cohort is a meaningful outcome. The safety profile across 32 patients completing 640 total sessions in a single day was clean.
The D-cycloserine augmentation component distinguishes this protocol from every other accelerated TMS study in the published literature. Its contribution to the outcome cannot be fully separated from the session structure in a single-arm trial, but prior randomized controlled trials of DCS augmentation in TMS have shown significant efficacy improvements, providing mechanistic plausibility for its role here.
Why this study matters for patients
The ONE-D study demonstrated for the first time that a complete and clinically meaningful course of TMS could be delivered safely in a single day. For patients whose schedules, geography, or circumstances make multi-day or multi-week protocols impractical, this represents a genuinely different level of accessibility. The protocol requires one clinic visit. The published results in treatment-resistant patients are the strongest response rates in the accelerated TMS literature.
Full text available at: https://doi.org/10.1016/j.tmsj.2025.100135
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