Depression Can Be Over In 6 Half-Days With No Drugs?!?
The FDA Says Yes, Today, to Accelerated dTMS, My Personal White Whale Since 2017.
The Frontier Psychiatrists newsletter might as well be the “Accelerated TMS Star Ledger” most days. Starting on July 11th, 2022, I was writing about the first accelerated TMS breakthrough treatment, SAINT. I subsequently jumped up and down (with the written word) when I cheered for the FDA-Breakthrough clearance for SAINT neuromodulation, which combines fMRI and 5 days of brief, 10 sessions a day brain stimulation, to get to a 79% remission rate.
Remission—it’s defined as scores on a rating scale below the threshold for having the illness. In a prior era, we’d say “cure.” We don’t use that word now, but that is what we are talking about. It’s a big deal. It’s not the biggest possible deal, such as “recovery” and having a full, rich, awesome life, which is a real goal, but it’s better than “less symptoms!” but still sick.
I don’t need to tell you that fMRIs are hard to get, though. 3-Tesla MRI machines are not a dime a dozen. It would be nice if we had an even more general technology that was capable of even greater scale than SAINT is capable of. I love SAINT, and we use it at our office in New York City already. However, I care a lot about the accessibility of treatments. If you follow this story and stick around till the end, I’ll compare SAINT and this accelerated H-coil treatment so you can sound smart at the holiday party.
Long-time readers will know that I was publishing about just such an approach using the “deep TMS” H-coil systems made by the company Brainsway. Yes, this is the TMS system that treated me. The first person in my life to benefit from TMS treatment? This guy:
I’ve been OBSESSED with solving this problem—if seemed absurd to keep doing this very effective treatment once a day only based on no good evidence that this was the only way to do it. People want to feel better more quickly, with less trips back and forth, my reasoning screamed out! We started collecting data, when we had patients who had no option other than to try the accelerated version of the treatment, and publishing those results. Dating back to case reports in 2018 (in bipolar disorder), another case report in 2019 (in an MDD patient)1, and, in 2020, published the humbly titled “ACCELERATED AND NON-ACCELERATED DTMS PROTOCOLS BOTH EFFECTIVE IN TREATMENT OF MDD,” which included:
107 patients, 21 received an accelerated protocol which consisted of, a range of 3 to 10, treatments in a day. The other 87 patients received a non-accelerated protocol.
And demonstrated similar outcomes in this real-world sample:
The performance of paired T-tests demonstrated an overall reduction of BDI scores in MDD patients, t(112)= 8.63, p < .01, d = 0.79. Paired T-tests showed a reduction in pre- and post-BDI scores in MDD patients who participated in an accelerated protocol, t(17)= 3.77, p < .01, d=0.86. Paired T-tests showed a reduction in pre and post-BDI scores in MDD patients who participated in a non-accelerated protocol, t(86) = 7.75, p < .01, d= 0.80.2
This was followed by multicenter post-marketing data showing other sites had replicated our early work on accelerated dTMS3:
With excellent durability in this real-world data set:
The six-month durability of accelerated Deep TMS is 93%.
This data suggested to my colleague, Dr. Tendler, that we should shoot for an FDA approval for an accelerated protocol using 5 stimulations a day over 6 total days, followed by a taper at the end. This was compared, per the FDA’s request, to the once-a-day active treatment that was already approved. This is called a “non-inferiority” design. My friend Dr. Jonathan Downar explains this idea quite nicely in a podcast here. This is what my co-authors and I did in an FDA approval trial, granted today.
This study was remarkable—in more ways than one. Most importantly, this study demonstrated that the accelerated version is wildly effective at ending depression in those for whom prior medicines and therapies hadn’t helped:
HDRS-21 depression scores, after statistical adjustment, were reduced by 19.02 and 19.79 points in the accelerated and standard Deep TMS groups, respectively; and response and remission rates were 87.8% and 78.0%, respectively, for the accelerated group
This is a GREAT result for a Treatment-Resistant Depression study. The other remarkable thing was the size of the trial—keep in mind, the SAINT pivotal trial only included 29 subjects total—15 in the active group, and 14 in the sham group. The study was stopped early by the IRB because it was deemed unethical (at the “midpoint” analysis) to continue to give sham treatment to human subjects when the active treatment was so remarkably effective.
This new trial, funded by study sponsor Brainsway, was much larger because it randomly assigned subjects to one active treatment or another active treatment. This means the risk of the trial getting shut down early was countered.
I was thrilled to be an author on this trial, collaborating with many dear friends, such as first author Colleen Hanlon, Ph.D, senior author Aron Tendler, M.D., with a special shout-out to Molly Davis, M.D., who enrolled a ton of subjects too!
We now have multiple studies making it blazingly clear that no one should have to keep suffering forever with depression, stuck in a rut, thinking that if medicine doesn’t work, there is no hope. In 80% of people, across multiple data sets, relief is waiting for you, using more than one variant of this modality.
More treatments exist, and are coming too. One addresses anhedonia and doesn’t hurt at all—brand name PRISM-MDD. Another, ProLivRx, can be done entirely at home. Let’s not forget psychedelics!
Oh, and how do SAINT and Accelerated dTMS compare? This is a cheat—these two studies don’t compare overlapping samples. The SNT FDA trial included only individuals with severely treatment resistant depression (The average was 13 failed medication trials and 20 years of depression!) The Accelerated Brainsway FDA trial was designed to mirror the original FDA clearance trial, and thus the inclusion and exclusion criteria mirror those—which were up to 5 years of depression, and more than 1 medication trial, but not more than 4 trials of medications. No Brainsway study patients would have been appropriate for the SNT trial, and vice versa. So, when people want to compare them, based on these two FDA trials? You can’t. These were conducted in totally different groups of patients, with the only thing in common being the diagnosis. It’s like asking to compare my experience in a hot tub versus the Atlantic—both involve being up to my neck in water, and the similarities end there.
Thanks for reading! This is the culmination of work in my life since 2017, and I want to thank each and every patient an study subject who consented to this treatment!
Accelerated dTMS—side effects may include becoming a TMS researcher.
If you are interested in treatment for depression with Accelerated H1 coil TMS, SAINT, or the Ampa OBSERVER open-label clinical trial…
Join us at Radial—where I work—we focus on next-generation treatments.
They include Spravato, Nightware, eTNS, PRISM Neurofeedback, soon, eCOT-AS by Neurolief, TMS, Accelerated TMS, and fMRI-guided SAINT TMS.
Radial offers the most advanced mental health care.
Muir, O., MacMillan, C., Khan, M., Sang, L., & Aron, T. (2019). Rapid remission of depression using sequential bilateral theta burst dTMS. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 12(4), e137.
Muir, O., Ruiz, D., Abbott-Sinclair, R., & MacMillan, C. (2020). Accelerated And Non-Accelerated dTMS Protocols Both Effective In Treatment Of MDD. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 13(6), 1854.
Roth, Y., Hanlon, C. A., Pell, G., Zibman, S., Harmelech, T., Muir, O. S., ... & Tendler, A. (2023). Real-world efficacy and safety of various accelerated deep TMS protocols for major depression. Psychiatry Research, 328, 115482.
Anyone who’s read this blog for more than a month knows the impact you’ve had on this clearance and we thank you.
And I prefer the Atlantic. Less Pseudomonas.
thank you for the shout out! It was the highlight of my career to be a part of this.