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

A new systematic review and meta-analysis of 59 studies and nearly 2900 patients found total pulse count tracked with better depression outcomes in an approximately linear, more-is-better pattern across sham-controlled trials of accelerated repetitive TMS (rTMS).¹

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 (P =.0034), response (P <.0001), and remission (P =.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 HCPLive. "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 a certain minimum.²

That minimum appears to sit around 1200 pulses, or roughly 3 minutes of theta-burst stimulation, Downar said. 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.²

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

Downar has no reported disclosures.

References

1. 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. Brain Stimul. 2026;19(4):103129. doi:10.1016/j.brs.2026.103129

2. Oostra E, Jazdzyk P, Vis V, et al. More rTMS pulses or more sessions? The impact on treatment outcome for treatment resistant depression. Acta Psychiatr Scand. 2025;151(4):485-505. doi:10.1111/acps.13768