Transcranial magnetic stimulation (TMS) has established itself as one of the most effective non-medication treatments for Major Depressive Disorder (MDD), particularly for patients who have not responded adequately to antidepressants. Over the past decade, research has focused not only on improving outcomes but on making TMS more efficient and accessible. A recently published case series in the journal Transcranial Magnetic Stimulation explores a striking idea: delivering an entire course of TMS treatment in a single day. The possibility of meaningful antidepressant effects after just one visit is worth taking seriously, but a close look at the data shows real limitations. At this stage, single-day TMS should be viewed as an early, exploratory approach, not a replacement for established protocols.
The Appeal of Single-Day TMS
Traditional TMS treatment requires a real time commitment: typically five sessions a week over six to eight weeks, for 36 or more total treatments. Even newer options like intermittent theta burst stimulation (iTBS), which shortens each individual session to a few minutes, still require daily visits over about six weeks. The idea behind single-day TMS is to compress that entire course into one intensive day of back-to-back sessions. If it worked as well as standard protocols, this could ease scheduling burdens and improve access for patients who cannot commit to weeks of daily visits. The reality, based on the available evidence, is more complicated.
What the Study Actually Tested
The study, known as the ONE-D regimen (Optimized, Neuroplasticity-Enhanced treatment for Depression), was a retrospective case series of 32 adults with unipolar Depression, treated at two community TMS clinics and drawn from a shared patient registry. It is important to understand exactly what this regimen involved, because it was not simply TMS delivered faster. Each patient received 20 iTBS sessions over roughly 9.5 hours, targeting the left dorsolateral prefrontal cortex, and each session was preceded by a single dose of two off-label medications: D-cycloserine, an NMDA receptor agonist thought to enhance neuroplasticity, and lisdexamfetamine, a psychostimulant. In other words, the single-day format tested in this study combined TMS with pharmacological augmentation rather than testing accelerated TMS alone. The study also used an investigational coil that had not yet received FDA clearance at the time data was collected.
What the Study Found
At six weeks post-treatment, the results were notably strong: 87.5% of patients met response criteria and 71.9% met remission criteria on the clinician-rated Hamilton Depression Rating Scale, with similarly high rates on self-reported measures. Side effects were common but mild: 78.1% of patients reported some side effects during treatment, most often headache or scalp discomfort, with an average discomfort rating of 5.8 out of 10, and there were no serious adverse events. By 12 weeks, most patients maintained their improvement. By 26 weeks, results were more mixed: half of patients showed sustained remission, while 25 to 28% had relapsed or been re-treated, depending on the measure used.
One detail matters more than it might first appear: the benefit was not immediate. Improvement followed a gradual, delayed trajectory, building slowly over the six weeks after the single day of treatment rather than appearing right away. This is a meaningful distinction from how the concept is often marketed.
An Important Nuance: Faster to Deliver Is Not the Same as Faster to Work
Single-day TMS is often described as though it would provide faster relief from Depression, since the treatment itself takes only one day. The data in this study point to something different. The clinical benefit still took weeks to fully develop, similar to the timeline for standard TMS. The study’s own authors contrasted this with rapid-acting interventions like ketamine or esketamine, which can improve mood within hours, and even with other accelerated multi-day protocols, where one earlier study reported a median time to remission of about 2.6 days. Compressing the number of clinic visits into a single day did not translate into a faster clinical response in this data set. It changed how quickly the treatment could be delivered, not how quickly it worked.
Why the Results Deserve a Careful Read
Several factors matter for interpreting this study responsibly. It was a retrospective case series with no placebo comparison and no blinding of patients or clinicians, so expectation effects cannot be ruled out. Patients in this sample received treatment free of charge on a compassionate basis, and the study’s own authors acknowledged that gratitude and expectation of success could have influenced self-reported outcomes. Thirteen of the 32 patients had previously responded to conventional TMS, a group more likely to respond well to any TMS regimen. The medication augmentation used, D-cycloserine and lisdexamfetamine, remains off-label for this purpose, and the study could not separate how much of the benefit came from the TMS itself versus the medications. Finally, several of the study’s authors disclosed financial relationships with the company that manufactures the TMS coil used in the research, which is worth knowing when weighing how the findings are framed.
How This Compares to Proven Accelerated TMS Protocols
It is worth distinguishing single-day TMS from other accelerated protocols that already have a stronger evidence base. Multi-day approaches that deliver several sessions per day over five to ten days, including FDA-cleared protocols modeled on the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), have shown high remission rates, more rapid symptom improvement, and a larger and more consistent body of supporting research. These protocols were also developed using personalized, imaging-based targeting rather than a standardized scalp-based estimate, which may help explain their faster onset of benefit.
Why Mid City TMS Does Not Currently Offer Single-Day TMS
At Mid City TMS, treatment decisions are grounded in evidence and patient safety. We follow developing research closely, but we do not adopt new protocols until they are supported by larger clinical trials, demonstrated durability, and reproducibility across multiple settings and patient populations. Single-day TMS, in its current form, does not yet meet that bar. Instead, we offer standard FDA-approved TMS protocols with well-established efficacy, accelerated multi-day protocols supported by a growing body of research, and iTBS, which shortens individual sessions while maintaining outcomes comparable to standard treatment.
Single-day TMS In the Future
Single-day TMS is a genuinely interesting area of research, and the ONE-D findings suggest that delivering an entire course of stimulation in one day, combined with pharmacological augmentation, is feasible and reasonably well tolerated. It is not yet established as equivalent to, or faster acting than, standard or multi-day accelerated protocols, and the current evidence comes from a small, unblinded, uncontrolled case series with some notable conflicts of interest to weigh. Patients deserve treatments that are convenient and proven to work and to last. If you are considering TMS, working with a clinical team that stays current with the evidence, rather than the marketing around it, matters.
Learn how Mid City TMS can help, or contact us today to discuss which evidence-based TMS approach may be right for you.
Sources
- Vaughn D, Marino B, Engelbertson A … Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplasticity-Enhanced techniques in Depression (ONE-D): An open-label case series. Transcranial Magnetic Stimulation, 2025; 5
- Schade, S., & Paulus, W. (2016). D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review. The international journal of neuropsychopharmacology, 19(4), pyv102. https://doi.org/10.1093/ijnp/pyv102