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Accelerated TMS Moves Toward Circuit-Based Depression Treatment
In a Q&A, psychiatrist Scott Wilke, MD, explains how accelerated TMS protocols are reshaping depression care and may help tailor treatment to specific neural circuits.
Although transcranial magnetic stimulation (TMS) has been FDA-approved for depression since 2008, investigators are still working to understand exactly how brain stimulation reshapes neural circuits to produce antidepressant effects. New preclinical findings published in Cell offer some of the clearest mechanistic evidence to date, suggesting accelerated intermittent theta burst stimulation (aiTBS) may selectively restore stress-disrupted brain circuitry rather than broadly activating the brain.1
In this Q&A, Scott Wilke, MD, assistant professor of psychiatry and the Penske Family Chair in Neuromodulation at UCLA Health, discusses how accelerated TMS protocols are beginning to change clinical practice, what the new research could mean for more personalized neuromodulation strategies in the future, and why clinicians should view TMS as an increasingly mainstream option for patients with treatment-resistant depression. Wilke also addresses ongoing barriers to access, realistic expectations for response timing, and where accelerated protocols may ultimately fit into psychiatric care.
HCPLive: Standard TMS has been around since 2008. When did accelerated protocols start feeling like a genuine paradigm shift rather than just an experimental tweak?
Wilke: Traditionally, people have thought of depression as something that takes weeks or months to improve. In the last 10 to 20 years, we've accumulated evidence that you can treat depression rapidly, and then with TMS treatments, we've started to use them in our clinic in the last year or two.
HCPLive: Your findings suggest TMS may work through more specific neural circuits than previously understood. Could this help explain why some patients respond well to TMS while others do not, and how might that shape more personalized approaches to treatment in the future?
Wilke: We thought maybe these TMS treatments are modulating all of the neurons similarly, and it's remarkable that what we find is that it's actually having distinct effects on distinct cell types. What would be really cool is if it turns out that we can tune the TMS treatment to target specific circuits and cell types.
HCPLive: Could you walk me through how you currently identify candidates for the accelerated protocol versus the standard schedule?
Wilke: The major limitation right now with accelerated treatments is that insurance companies typically don't cover accelerated treatment. It's important to underline the fact that standard treatment is still the gold-standard approach to depression.
One of the variables is [that] some people just can't make it in for one treatment every day for 6 or 7 weeks. It's too difficult with their schedule, but they might be able to set aside 1 day or 1 week where they could come. In those cases, we might direct people towards accelerated treatment.
The other [limitation] is…an access issue with TMS clinics. We often run into the situation where someone lives far away, and driving [to] the clinic every day for that long is really burdensome for them. But again, that's a situation where they could come and maybe stay in the area for a week and get an accelerated treatment.
It's too early to start talking about this clinically, but there may be cases that are more acute, where the consequences of not treating the depression…could be so dire that you really need an accelerated treatment. Accelerated treatments might find a role in the hospital when people are [in an] inpatient psychiatry unit or maybe even in the emergency department.
HCPLive: Response timing seems underappreciated, with some patients taking days or weeks to feel benefit. How do you prepare patients for that, and how do you prevent premature dropout?
Wilke: It's important for people to have a realistic understanding of what might happen with treatment. I always prepare patients for that. You start with something that you think is most likely to work. We think it takes about 5 to 10 treatment sessions before we really know if we're on the right track or not. People should know that they could start improving within the first week or two, but if they're not improving, there are adjustments that we can make to try to get the TMS treatment working better.
Importantly, people shouldn't become frustrated if they're not getting better right away. We definitely see patients get better halfway… [or] three-quarters of the way through. Even some patients who've done the whole treatment course and say they're not much better… [will] come back 6 months later and say that they actually did find that even after the treatment was over, they continued to improve and had a significant benefit.
HCPLive: For a psychiatrist with a treatment-resistant patient in front of them right now who has failed two or three antidepressants, what do you want them to know about what's available today?
Wilke: It's a really exciting time for depression treatment. I can't think of a time in my career where I had more hope for those patients [who] weren't responding to medications. [It] used to be that there's just 1 or maybe 2 things that people could try at that point, for example, electroconvulsive therapy, which is effective but has a lot of potential side effects.
What I would communicate to clinicians is that this is not an experimental approach at this point. It's not a last-ditch effort to get people better. This is a legitimate treatment that probably should be considered in the future, something you should do earlier when people are depressed… [and] if they aren't responding to medications. It can [even be] an alternative path for people who would prefer not to take medications. The insurance structure right now doesn't typically allow that, but… we may find that that shifts over time.
TMS is really the best… next step…for someone who has not responded to antidepressant medications. This is a field that is rapidly evolving now, and I think there's going to be a lot of exciting changes in the coming years that will make this an even more attractive route for patients.
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