Is Faster Brain Stimulation Better?

If one simple innovation can make a product 10 times faster without sacrificing performance, that would be considered a monumental breakthrough in many technological circles. Such an innovation occurred in psychiatry last year when the Food and Drug Administration (FDA) cleared a new form of transcranial magnetic stimulation (TMS) for treatment-resistant depression that requires only three minutes per session—as opposed to up to 40 minutes needed for conventional TMS therapy.

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The arrival of this rapid neuromodulation approach, known as theta-burst stimulation (TBS), could significantly increase access to a proven depression therapy because more patients can be treated at TMS clinics every day. But as TBS-capable machines become more widely available (the 2018 FDA clearance was specifically for TBS on MagVenture devices, but this past March Magstim systems also were allowed to include TBS), it remains unclear whether shorter stimulation equals better stimulation.

From a scientific perspective, at least, the advent of TBS is an important milestone, said Mark George, M.D., the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina in Charleston and a pioneer in using TMS to treat depression.

Conventional TMS pulses magnetic waves at a frequency of 10 hertz (Hz), typically for 5 to 10 seconds. These pulses are continually repeated with short breaks in between for 20 to 40 minutes depending on the machine—hence why the treatment is referred to as repetitive TMS.

George, who led much of the preclinical research with TMS as a depression therapy, acknowledged that the 10 Hz level was chosen more by art than science. “As scientists we are fond of base 10, and we just tested a range of frequencies ending in 0 or 5 and found that 10 Hz was both safe and effective,” he told Psychiatric News. “We figured once researchers got smarter about how the brain works, we would pick a more optimal frequency.”

If TBS is magnetic stimulation optimized, then that frequency is 50 Hz, delivered in three, rapid bursts totaling a fraction of a second. This pattern mimics the natural theta waves fired off by neurons in the brain. “If you could somehow just listen in on the brain talking, these rapid-fire bursts are the sounds you would hear,” George said.

TBS allows physicians to speak back in the same language, George continued. By generating magnetic waves more in sync with natural rhythms, neurons can become stimulated much more quickly—in three minutes, or even faster.

TBS, Repetitive TMS Have Similar Benefits, Risks

Following success in some preliminary studies, the clinical efficacy of TBS was confirmed in a large, multisite, head-to-head study that compared TBS to the clinically available standard: repetitive 10-Hz TMS. The study findings were published in Lancet in April 2018.

“I believe it was at the time the largest brain stimulation study ever conducted,” said Daniel Blumberger, M.D., co-director of the Temerty Centre for Therapeutic Brain Intervention at Toronto’s Centre for Addiction and Mental Health (CAMH) and lead investigator of the comparative study. “And the results showed that in terms of benefits and side effects, these two treatments were identical. This new method of delivery is just far more efficient.”

George noted that the study compared two active treatments, and patients knew which one they were receiving. “The rigid scientist in me always prefers if we can do studies with a genuine control condition so we can see how well an intervention works. The study did not demonstrate that either TMS delivery method worked well; it only showed that the two approaches look to be the same. It was not the highest level of science,” he said.

“The clinician in me, however, is still excited that this new method is now ready for public use,” he continued.

Will Shorter Procedure Impact Patients?

Some remain skeptical about how revolutionary TBS might be. TMS providers will surely benefit as they can now offer more treatment sessions per day using the same machines. However, it won’t reach a level wherein TMS clinics turn into drive-thru services where people can roll in and out. For one, magnetic coils heat up quickly when they generate rapid theta bursts and will require regular cool-down periods. Also, every clinic visit still requires other tasks like taking patients’ vitals and getting them situated in the machine. Still, patient capacity will increase substantially.

Offering more services per day is unlikely to drive down costs, said Adam Chekroud, Ph.D., an assistant professor of psychiatry at Yale University and co-founder of Spring Health, a startup that looks to improve mental wellness programs at workplaces. “Medical reimbursement is usually priced in a value-based or reference- based manner; that is, what is the treatment worth or what is the charge for a comparable alternative?” he explained. Though TBS is a shorter procedure, it is comparable to regular TMS in terms of effectiveness, so costs are likely to remain the same.

Chekroud also wonders if session time is really the most pressing issue in TMS therapy. “If TMS becomes a treatment option in a busy general practice/primary care setting, then a quick turnaround could be useful,” he said. “But TMS is meant to be a solution for treatment-resistant depression. The issue for that patient population and those providers that treat them isn’t a lack of time, it’s that these patients have complex conditions that don’t respond with any amount of time.”

Blumberger disagrees with these assessments. “I cannot control how a treatment gets reimbursed, but even at an equal cost, the shorter duration of TBS creates more flexibility for patients, as they don’t need to block out a couple of hours for each session. Over the course of weeks and months, that adds up,” he said, noting that the patients he has seen so far have been receptive of the shorter method.

“The other avenue TBS has opened is that it now becomes more feasible to provide [a patient with] multiple treatments per day, which could improve symptoms faster,” Blumberger added. TMS sessions are currently administered two or three times each week to avoid possible side effects; however, there is no evidence that providing sessions closer together is an issue. (The caution comes from clinical experience with electroconvulsive therapy, which can cause cognitive problems if administered too frequently.)

It’s an appealing idea, but George warns that TBS is less reliable when given repeatedly. Using steady 10 Hz pulses takes longer, but a repetitive TMS session will stimulate the brain every single time. In contrast, if a second TBS session is given too quickly, it might undo some of the positive effects of the first session.

“That is just one of many outstanding questions we need to address,” Blumberger agreed. “And we also need to acknowledge that TBS is not going to work for everyone, so I don’t see it as a replacement for repetitive TMS. But it does provide another option for physicians that puts TMS on the road to becoming a personalized treatment where we can find the right pattern of stimulation for each individual.” ■