The ONE-D study: a complete course of TMS in one day what the research showed
The ONE-D study: a complete course of TMS in one day and what the research showed
Most patients who come to us asking about TMS have a version of the same concern: the schedule. Six weeks of daily clinic visits is a genuine barrier for working parents, for people in demanding jobs, for patients who live far from a clinic, for anyone whose life doesn't have thirty-six empty weekday mornings available over the next month and a half.
The five-day intensive addresses part of that problem. One week instead of six. But even five consecutive days requires planning travel, accommodation, time away from work or family.
The ONE-D study asked a different question: what if you could do all of it in one day?
The answer, published in 2025 in the Transcranial Magnetic Stimulation Journal, was yes with published response rates that exceeded anything previously reported in accelerated TMS research.
Where the idea came from
What D-cycloserine actually does
What the trial found
Being honest about the study's limitations
What the day actually looks like
Who this protocol is most right for
How the ONE-D compares to the Five-Day Intensive
Why we offer this protocol
Where the idea came from
The foundational insight behind the ONE-D protocol is the same one behind the SAINT protocol: neuroplasticity windows. Each iTBS session opens a period of heightened synaptic responsiveness. The next session, timed to arrive while that window is still open, compounds on the previous one rather than starting from baseline.
The SAINT protocol spaces ten sessions per day over five days fifty sessions total across a week. The ONE-D researchers asked whether the same compounding logic could be pushed further: twenty sessions in a single day, spaced thirty minutes apart, with a neuroplasticity-enhancing agent taken before each session to keep the plasticity machinery primed throughout.
That agent is D-cycloserine.
What D-cycloserine actually does
D-cycloserine is a partial agonist at the NMDA receptor, a receptor type central to synaptic plasticity and learning. At the low doses used in this protocol, DCS doesn't produce meaningful psychological effects on its own. What it does is lower the threshold for neuroplastic change: making neurons more responsive to the activity-driven synaptic strengthening that TMS is trying to induce.
Prior randomized controlled trials had already established that DCS augmentation of TMS improves outcomes. A 2022 randomized clinical trial published in JAMA Psychiatry by Cole, Sohn and colleagues found that DCS augmentation of iTBS significantly improved remission rates compared to iTBS alone from approximately 18% remission in the unaugmented group to meaningfully higher rates with DCS. The ONE-D protocol takes that finding and applies it across all twenty sessions of a single treatment day maximizing the neuroplasticity window not just for one session but for the entire day of treatment.
DCS has a well-established safety record. It was originally developed as an antibiotic for tuberculosis and has been used in psychiatric research for decades. At the doses used here it is not a psychiatric drug in the conventional sense, it is a neuroplasticity primer, and its mechanism is coherent with the biological framework that explains why TMS works.
What the trial found
The ONE-D study enrolled 32 patients with treatment-resistant major depressive disorder. All 32 completed the full one-day protocol, a 100% completion rate that is itself a meaningful data point about tolerability. No serious adverse events were reported.
The primary outcome measures at six weeks: 87.5% response rate, meaning 87.5% of patients showed clinically meaningful reduction in depression symptoms, 71.9% remission rate meaning nearly three in four patients met criteria for minimal depressive symptoms
At twelve weeks: 84.4% response rate response was maintained and in some cases continued to improve 50% sustained remission at six months half the cohort remained in remission six months after a single treatment day
The response trajectory followed the expected neuroplasticity consolidation curve, gradual improvement building over weeks four through six rather than immediate post-treatment relief. This is consistent with the biology: the brain is rewiring, not responding to a drug that's present in the system, and structural consolidation takes time even when the treatment that initiated it is complete.
Tolerability data from the trial: mean discomfort during treatment was rated 5.8 out of 10. That's real a full day of iTBS sessions involves a genuine scalp sensation but it was well-tolerated across all 32 participants. No one stopped treatment due to discomfort.
Being honest about the study's limitations
The ONE-D study is a small, open-label trial. Thirty-two patients is not a large sample, and without a sham control group, a group of patients receiving inactive treatment for comparison, the results cannot definitively isolate how much of the effect was treatment-specific versus expectation effects or natural variation in depression course.
This is the study's most significant methodological limitation, and the authors acknowledge it directly. Open-label trials without sham controls consistently show higher effect sizes than blinded controlled trials, partly because expectation effects are real and partly because unblinded outcome ratings can introduce bias even in well-conducted studies.
What we can say honestly: the response and remission rates are the highest published for any TMS protocol, in a treatment-resistant population, with a clean safety profile across 640 total sessions in a single day. The six-month durability data is consistent with the durability literature for accelerated TMS more broadly. The DCS augmentation rationale is mechanistically sound and supported by prior controlled trial data. And the completion rate 100%, no dropouts speaks to the tolerability of the protocol even across a long treatment day.
A sham-controlled RCT of the ONE-D protocol would be the definitive next step. Until that data exists, the ONE-D results should be understood as a highly promising signal from a well-designed pilot study rather than a fully established efficacy claim.
We cite these results on our site because they are the best available published data for this protocol. We note their limitations because you deserve that context.
What the day actually looks like
Twenty sessions over approximately 9.5 hours sounds demanding. In practice, it's structured and more manageable than it sounds.
Each iTBS session takes approximately three minutes of active stimulation. The thirty-minute inter-session intervals are yours to read, rest, watch something, eat, or talk with our team. You're in a comfortable reclining chair. The stimulation involves a rhythmic tapping sensation on the scalp that most patients find unusual but tolerable, and that typically becomes more comfortable as the day progresses.
The day is long. There's no point pretending otherwise. But it is one day not thirty-six, not five. You arrive in the morning, you leave in the afternoon or early evening, and your treatment is complete.
You will not be sedated. You can drive yourself home. A companion is welcome for part or all of the day, and many patients appreciate having someone there, particularly during the afternoon sessions when the cumulative fatigue of a long clinic day is most noticeable.
Who this protocol is most right for
The One-Day Intensive is the strongest fit for patients who:
Cannot commit to five consecutive days or six weeks of visits due to schedule, geography, or life circumstances, Want the most time-efficient path through a complete TMS course, Are interested in the neuroplasticity-enhancing benefits of D-cycloserine augmentation, Have treatment-resistant depression or have not found adequate relief through prior medication trials, Are traveling from out of state and want to complete treatment in a single visit
It may be less ideal for patients who: Have significant difficulty sitting for extended periods, Are primarily motivated by the largest possible published trial behind their treatment, in that case, the Five-Day Intensive has the more rigorous study design behind it, Are hoping to use insurance, as this protocol is cash-pay
How the ONE-D compares to the Five-Day Intensive
Both protocols are accelerated iTBS. Both are modeled after published research. Both are cash-pay. The differences worth understanding:
Session structure: ONE-D delivers 20 sessions in one day; Five-Day delivers 50 sessions across five days. The Five-Day has a higher total session count.
Augmentation: ONE-D uses D-cycloserine before every session. The Five-Day Intensive as we deliver it does not include DCS augmentation it follows the SAINT session structure.
Evidence base: The SAINT/SNT trial was a randomized, double-blind, sham-controlled study. The ONE-D trial was open-label without a sham arm. The SAINT trial design is more rigorous. The ONE-D response rates are numerically higher. Both findings are in treatment-resistant populations.
Time commitment: One day versus five consecutive days.
Cost: $2,995 versus $7,995.
Neither protocol is objectively superior to the other across all patients and all circumstances. The right choice depends on your schedule, your budget, your clinical history, and your provider's assessment of which protocol fits your presentation. That's what a consultation is for.
Why we offer this protocol
The ONE-D study represents something genuinely new in TMS: a single-visit complete treatment course with published outcomes that rival or exceed anything else in the accelerated TMS literature. For patients who need treatment but can't do five weeks or five days, it isn't a compromise it's a different clinical tool with its own compelling evidence base.
We offer it because the published data warranted it and because our clinical philosophy has always been to give patients the most effective options available, not the most convenient ones to schedule. One day happens to be both.
We are not affiliated with the ONE-D study authors or their institutions. Our protocol is modeled after their published methodology.
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