Jonathan Downar, MD, PhD, FRCPC, associate professor of the Department of Psychiatry at the University of Toronto and co-founder of Ampa.

Jonathan Downar, MD, PhD

Jonathan Downar, MD, trial investigator of a new meta-analysis on dosing in accelerated repetitive TMS (rTMS) for 

, said a purpose-built randomized controlled trial (RCT) is still needed to confirm optimal pulse count and intersession spacing. The current safety data leaves room to explore higher pulse doses in future protocol design.

“The first one would be for us to do a proper randomized trial looking at whether it's worthwhile to do more than the 3 minutes," said Downar, associate professor of psychiatry at the University of Toronto, in an interview with 

 "The second big question would be…to try and figure out how long [it is] ideal to wait between sessions."

What the Next Accelerated TMS Trial Should Test, With Jonathan Downar, MD

The meta-analysis found a roughly linear relationship between total pulse count and outcomes in sham-controlled trials. Total pulses significantly predicted symptom improvement (

Designing a Trial to Test Pulse Count and Intersession Timing

Downar said the field already has strong evidence behind a 3-minute theta-burst protocol, making the first open question whether extending sessions to 1200 or 1800 pulses adds meaningful benefit or simply adds time in the chair. He acknowledged RCTs are expensive and slow to run but called this comparison the more straightforward of the 2 questions to settle.

The second, harder question involves intersession interval, where Downar expects meaningful variability from person to person, consistent with most factors in neurophysiology. He raised the possibility of eventually developing a biomarker or brief test session to identify each patient's ideal spacing, but said the near-term goal is simpler: finding the shortest interval that still works for the large majority of patients, whether that turns out to be 60, 40, 30, or fewer minutes.

“Until that point, all we can do is try to do meta-analyses to put together different studies that have used different intervals and see how they do,” Downar said.

Pulse Count Safety and the Takeaway for Community Psychiatrists

On safety, Downar cited the SAINT protocol developed by Nolan Williams, MD, and colleagues at Stanford, which delivers 1800 theta-burst pulses hourly for 10 hours a day, roughly 18,000 pulses daily. Whether going meaningfully higher, to 36,000 or 72,000 pulses a day, remains untested, he said, since few published protocols exceed about 18,000 pulses in a single day.

Downar described TMS overall as a safe treatment, noting patients in his own clinic have received hundreds of sessions over more than a decade without an apparent upper limit. He also flagged low-frequency protocols, delivered below 5 Hz, as an underexplored area with an established safety record around seizure risk, worth watching as dose-response rules are tested outside high-frequency and theta-burst protocols.

For clinicians outside the dose-response literature, Downar's advice is to lean on FDA-cleared protocols backed by large trials: the 3-minute theta-burst protocol from THREE-D and a 60-minute intersession interval for accelerated courses.

Emerging evidence on 30-minute, and even shorter, intervals is worth watching, he said, but not yet required reading for routine practice.

This is part 3 of a 3-part series with Jonathan Downar, MD. Read parts 1 and 2 for his perspective on 2 decades of TMS practice and a closer look at the new dose-response meta-analysis here:

TMS Sessions Reduced From 38 Minutes to 3, With Jonathan Downar, MD, PhD

More TMS Pulses Track with Better Depression Outcomes, With Jonathan Downar, MD

Wang VX, Mehta DD, Downar J, Tang VM, Li CT, Le Foll B. Dose-response associations of total pulse dose and intersession interval with clinical outcomes in accelerated rTMS for major depressive episodes: A systematic review and meta-analysis. 

More TMS Pulses Track with Better Depression Outcomes, With Jonathan Downar, MD. HCPLive. Published August 26, 2026. Accessed August 26, 2026. 

https://www.hcplive.com/view/more-tms-pulses-better-depression-outcomes-jonathan-downar-md

Blumberger DM, Vila-Rodriguez F, Thorpe KE, et al. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. 

Chen L, Klooster DCW, Tik M, et al. Accelerated Repetitive Transcranial Magnetic Stimulation to Treat Major Depression: The Past, Present, and Future. 

Videos

Downar outlines the randomized trial needed to confirm optimal TMS dosing and addresses a safety ceiling on total pulses.

A new systematic review and meta-analysis of 59 studies and nearly 2900 patients found total pulse count tracked with better 

outcomes in an approximately linear, more-is-better pattern across sham-controlled trials of accelerated repetitive TMS (rTMS).

The analysis is the first attempt to systematically model intersession interval, the spacing between same-day treatment sessions, across the accelerated rTMS literature. In sham-controlled trials, total pulses significantly predicted symptom improvement (

 =.0043), with negligible heterogeneity across studies.

"We know that in the brain there is a refractory period," investigator Jonathan Downar, MD, PhD, associate professor of psychiatry at the University of Toronto, told 

. "When you stimulate the brain with TMS for a certain number of minutes and induce some plasticity, there is a refractory period where you need to wait a certain amount of time before going back and doing the next session."

A Linear Dose Signal, With a Known Ceiling on Pulses Per Session

Downar said the linear pulse-response relationship in sham-controlled trials generally matches expectations, though the picture is more nuanced within a single session. He pointed to an earlier meta-analysis, published roughly a year and a half before his group's paper, which found that once researchers accounted for the number of sessions, progress tracked mostly with session count rather than pulses added within a session.

Beyond it, adding pulses to a single session does not reliably add benefit, which is part of why his group modeled total pulses across an entire course of treatment rather than pulses per session alone.

Why Intersession Interval Became the Study's Second Focus

Downar said the original clinical question behind the paper was practical: if some patients need 50 or 60 sessions to respond, asking them to make 50 or 60 separate clinic visits is a significant burden. Compressing sessions into fewer days requires knowing how long a synapse needs to rest between stimulations before the next session adds independent value, rather than blurring into the last one. Decades of animal literature suggested synapses respond best with 60 to 90 minutes of rest between stimulations, a concept Downar compared to spaced learning.

“With patients we sometimes talk about this toilet bowl example, where if you flush multiple times, you actually just get one flush,” Downar said. “You have to flush… and wait a certain amount of time for the tank to recycle before you can [flush] again. It's a silly analogy, but it is one that allows people to understand why [we] provide some stimulation and then…wait for a certain refractory period for the system to reset before [we] can go in and do it again.”

Read part 1 of this series for Downar's perspective on 2 decades of TMS practice: 

Oostra E, Jazdzyk P, Vis V, et al. More rTMS pulses or more sessions? The impact on treatment outcome for treatment resistant depression. 

A new meta-analysis found total pulse count predicted outcomes in a roughly linear pattern across sham-controlled trials of accelerated rTMS.

Do More TMS Pulses Track with Better Depression Outcomes?

Two decades of incremental advances have compressed transcranial magnetic stimulation (TMS) sessions from nearly 40 minutes down to as little as 3, expanding the treatment’s reach to far more patients with 

and other psychiatric conditions, according to Jonathan Downar, MD, PhD, associate professor of psychiatry at the University of Toronto and co-founder of Ampa One, an FDA-cleared TMS device.

Downar has practiced TMS since 2010, when he opened an academic clinic in Toronto, which eventually grew to treat up to 1000 patients annually across 10 machines before the onset of the COVID pandemic. He described the field's progress as steady rather than sudden, with a meaningful development arriving every 2 to 3 years since he entered the field.

"In 2010, when I started, TMS sessions were typically 38 minutes long, and over time we were able to discover ways to get them down to about 3 minutes per session, which allowed a lot more patients to come in and made it a lot more scalable," Downar said.

Shrinking Session Time Expands Patient Access

Downar pointed to 2010 as the year the first accelerated TMS study appeared in the literature, describing a protocol delivering 15 sessions over 2 days.

He called reducing the number of clinic visits required to complete a course of treatment one of the field's biggest ongoing priorities.

A second theme Downar highlighted involves pharmacologically enhancing plasticity. He said certain medications acting on specific brain receptors may boost the effect of TMS, potentially extending how long a course of treatment remains effective or lowering the number of sessions needed to achieve it.

Downar also credited advances in neuroimaging, an area tied to his own early research background, with reshaping which brain circuits clinicians target. Over the past 5 to 10 years, imaging studies have generated increasingly detailed maps of the circuitry implicated in depression and other psychiatric conditions.

The THREE-D Trial Set the Template for Shorter Protocols

Downar served as senior author on THREE-D, the 2018 trial published in The Lancet establishing a 3-minute theta-burst protocol as noninferior to older, longer stimulation regimens.

 He said the trial's legacy is visible today in the global adoption of theta-burst-based protocols, with clinicians in many regions now running sessions lasting 3 to 10 minutes instead of 37 minutes or more.

The time saved by shorter sessions has opened a new clinical question, Downar said: what to do with the extra time in a patient visit. Clinicians have begun using it to stimulate more of the brain during a single visit. A recent analysis has shown that 5x5 accelerated repetitive TMS, consisting of 5 sessions per day over 5 consecutive days, compresses overall treatment time from 6 to 1 week.

"Being able to complete an effective session or treatment in 3 minutes allows you to start thinking about things like doing multiple sessions per day or targeting multiple brain areas," Downar said.

This is part 1 of a 3-part interview series with Jonathan Downar, MD, on TMS practice and his group's new meta-analysis on dosing in accelerated rTMS.

Holtzheimer PE 3rd, McDonald WM, Mufti M, et al. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. 

Goldstein-Piekarski AN, Ball TM, Samara Z, et al. Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety. 

Derman C. TMS for MDD Reimagined: Faster, Fewer Visits, and Now at Home. HCPLive. Published May 15, 2026. Accessed August 25, 2026. 

https://www.hcplive.com/view/tms-mdd-faster-fewer-visits-home

Downar says shorter sessions, accelerated schedules, and expanding neuroimaging maps have made TMS effective for more patients in far fewer visits.

Jonathan Downar, MD, PhD

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