Accelerated 5×5 rTMS Matches Standard Protocols in TRD, With Andrew Leuchter, MD

New data showed accelerated repetitive transcranial magnetic stimulation (rTMS) may offer a time-efficient alternative to conventional protocols for treatment-resistant depression (TRD), delivering treatment in as little as 1 week rather than the standard 6-week course.1,2

“We know enough to know that accelerated treatment works very well,” investigator Andrew Leuchter, MD, a professor and director of the neuromodulation division at UCLA TMS Clinical and Research Service, told HCPLive. “I think the major thing that's holding us back from doing accelerated treatment more is just the fact that insurance companies will not reimburse for it. Medicare will pay for up to 2 sessions per day, but no more. What we need is for insurance companies to step up and allow us to be reimbursed for between 5 and 10 sessions per day, and I think that once the reimbursement is in place, you'll see accelerated treatment move up the list of treatment options.

In a retrospective analysis of 175 patients with major depressive disorder (MDD), investigators compared an accelerated “5 × 5” approach (n = 40), consisting of 5 sessions per day over 5 consecutive days, with a conventional once-daily rTMS protocol (n = 135). Both groups experienced clinically meaningful reductions in depressive symptoms, with no statistically significant difference in overall improvement between protocols (P =.07).

Mean Patient Health Questionnaire-9 (PHQ-9) scores declined from 17.68 to 10.98 in the accelerated group and from 17.83 to 8.97 in the conventional group by the end of treatment. Response rates were 37.5% in the accelerated cohort and 58.5% in the conventional group, whereas remission rates were comparable at 22.5% and 24%, respectively.

The analysis identified variability in response timing. While some patients experienced early improvement during the 5-day accelerated protocol, others demonstrated delayed benefit. Among initial non-responders in the accelerated group, depressive symptoms improved by 36% at 2 to 4 weeks post-treatment (P =.001), highlighting the importance of follow-up when assessing treatment efficacy.

In his interview, Leuchter emphasized that predicting response to rTMS remains a key clinical challenge. Commonly considered factors, such as illness severity, duration of disease, and prior treatment failures, have not reliably differentiated early from delayed responders. As a result, clinicians currently lack robust tools to guide patient selection or set expectations regarding treatment trajectory.

The study also contributes to ongoing efforts to optimize stimulation parameters. Investigators evaluated prolonged intermittent theta burst stimulation (piTBS), increasing pulse delivery from the standard 600 pulses to 1800 pulses per session. Leuchter noted that this higher-dose approach may enhance therapeutic benefit while maintaining brief treatment sessions of approximately 9 minutes.

“What we really need to do is to compare different kinds of stimulation in head-to-head studies and to identify what is going to be the most effective form of stimulation,” Leuchter said. “Right now, this prolonged intermittent theta burst, where we have a little bit longer session, looks like it's very effective. When I say a little bit longer, it's still only a 9-minute treatment session, so it really doesn't take that long, but it can be tremendously effective.”

Leuchter’s reported disclosure includes Abbott Laboratories.

References

1. Apostol MR, Valles TE, Corlier J, et al. Efficacy of 5 × 5 accelerated versus conventional repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression. J Affect Disord. 2026;403:121345. doi:10.1016/j.jad.2026.121345

2. Derman C. Accelerated Deep TMS Matches Standard Outcomes in TRD in 6 Days. HCPLive. Published March 18, 2026. Accessed on March 18, 2026. https://www.hcplive.com/view/accelerated-deep-tms-matches-standard-outcomes-trd-6-days