In pharmacology when a new drug is developed, and after its basic safety is demonstrated in a phase 1 clinical study, a dose “response curve” is established. This means the dose of the drug is systematically increased until either the response plateaus, meaning a higher drug dose does not provide any additional benefit, or significant side effects develop.
This “response curve” was never initially studied with TMS. However, new protocols and clinical studies are showing that adjusting the session frequency and intensifying the treatments has produced some exciting results.
The standard protocol for TMS for depression is 2340 pulsed stimulations per treatment session, at the left dorsal lateral prefrontal cortex (LDLPFC). An average treatment course is 30 sessions, one per day, 5 treatments per week over six weeks, providing slightly more than 60,000 stimulations. Each treatment lasts 20 to 40 minutes. This protocol has proven effective for many patients.
In 2018, a new theta burst protocol, which delivers 600 pulses over 3 minutes to the LDLPFC was approved and subsequently shown to be equivalent in efficacy to the standard protocol. The same six week course is used, one treatment per day, 5 treatments per week. This provides 18,000 stimulations.
With the hope of getting a more robust response, clinicians have recently been routinely increasing the number of theta burst stimulations by either performing more than 600 stimulations per session at the LDLPFC, or targeting a different brain structure (such as the midline) with additional stimulations. While it has not yet been confirmed with double blind studies, there is some agreement that various protocol extensions and enhancements lead to a higher percentage of patients reaching remission.
In 2019 a more aggressive treatment was developed, called the SAINT protocol. This protocol was given in 10 treatment sessions per day, for only 5 days total, 1800 stimulations per treatment. The treatments were separated by about an hour to allow brain tissue to repolarize. This protocol delivered 18,000 stimulations per day, or 90,000 stimulations over the course of a week—a much higher number of stimulations than previously administered in TMS treatment. This was performed with depression and suicidal patients in an inpatient setting and monitored closely because of safety concerns. The protocol was effective. More importantly, it was shown to be very safe, with no greater complications than that of standard TMS.
Subsequently the same protocol with 90,000 stimulations was tried for difficult-to-treat depression patients in an outpatient setting in a study at Stanford University. The result of the study showed a 90 percent response/remission rate, with no seizures or other significant complications. The 90 percent remission rate of depression in this study is the highest ever achieved with TMS.
While this study has not yet been replicated, these data are highly encouraging. The protocol has been used off label clinically in hundreds of patients, many in California, with good results and no safety concerns. It is important to note this protocol has not been submitted to the FDA for clearance, and therefore must be considered off label and experimental.
TMS Center of Colorado psychiatrists have used this protocol with a number of patients in the Denver office, with very good results. This approach has since been called Accelerated TMS. The one-week protocol can also be amended to be delivered over 2 weeks, with 5 treatments per day instead of 10. This makes it easier to tolerate and more convenient for some patients. The important factor is to deliver 90,000 stimulations to the LDLPFC over a one- to two-week period. In addition, the one-hour waiting period between treatments is essential.
The advantages of this approach are twofold. The first is that remission from difficult-to-treat depression can now be achieved within one to two weeks versus the four- to eight-weeks previously required. Given the level of suffering, morbidity and mortality of severe depression, a notably quicker treatment is a major advance. Second, results suggest that this approach may actually be more effective than standard TMS.
There are other factors besides the number of stimulations to consider with TMS, including the brain structures treated, the intensity of each stimulation, and more. Patients need to evaluate various TMS approaches and with the help of their psychiatrist to decide what is best for them.
At TMS Center of Colorado all treatments are performed using the Brainsway deep TMS device, which uses an H-coil. The stimulations generated by the H-coil go deeper into the brain and cover a larger area. The many advantages of the Brainsway H-coil over the standard figure-8 coil, which is used in all other TMS devices, are discussed in detail here.
The staff at TMS Center of Colorado and I are optimistic that this new protocol represents a significant paradigm shift in TMS therapy and will help more patients realize the life-changing benefits of deep TMS for depression and other mental health disorders faster and more effectively.
–Dr. Ted Wirecki
Chief Medical Officer, TMS Center of Colorado
Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment Resistant Depression
American Journal of Psychiatry 2020 Aug 1;177(8): 716-726