Breakthrough in brain stimulation offers cautious hope for depression
A radically different approach to transcranial magnetic stimulation holds promise, but requires further study.
The basic tools we have for dealing with depression haven’t changed much in recent years. Medication and talking therapies are a mainstay. Lifestyle approaches, such as encouraging physical activity, adequate sleep, and social connections, are often part of the package. If depression fails to go away, the next line of treatment for some may be a non-invasive form of brain stimulation called transcranial magnetic stimulation (TMS) which is helpful in some cases and has very few side effects.
Still, TMS requires a serious time commitment – typically a total of 36 sessions over six to nine weeks. Studies show that about a third of people who try it find it completely relieves their depression. Recently, a small, short-term study in the American Journal of Psychiatry suggested that a radical overhaul of the way TMS is administered could greatly increase efficacy while shortening the treatment period to just five days.
What is transcranial magnetic stimulation?
Certain areas of the brain are known to be involved in depression and other mood disorders. TMS uses powerful electromagnets to safely activate these regions. A device positioned on the upper part of the forehead delivers short electromagnetic pulses. These travel through the skull to stimulate nerve cells in the targeted area. Over time, this technique leaves that part of the brain more active, which would then affect entire brain networks responsible for mood regulation.
The most common side effect is a headache or temporary discomfort at the stimulation site. The most serious and rare potential side effect is seizures.
How effective is standard TMS for depression?
Despite progress since 2008, when the FDA first cleared a TMS device to treat depression, not everyone finds TMS to be effective.
When considering treatment options, it helps to understand the difference between response and remission. Symptoms of depression are often measured using tools such as the Hamilton Depression Rating Scale. Response to treatment means a reduction of 50% or more in symptoms; remission means the absence of symptoms defined in each scale.
Combined research on the standard TMS shows that about 30% of people experience complete remission from depression. This number varies somewhat between studies, devices and treatment protocols. Notably, however, when antidepressants have failed to relieve depression, even this modest rate of remission is higher than one would expect if a person simply tried a different drug.
When TMS helps, depression begins to subside after a few weeks and continues to improve throughout treatment. These benefits last about a year, on average. If the depression returns, another course of MSD or a different treatment is often necessary.
The staggering promise of the SAINT protocol
Stanford researchers have modified standard TMS techniques to create a new protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT or SNT), which
- uses MRI to select what is likely to be the optimal place in the brain for stimulation
- triples the number of pulses per session
- increases the number of sessions to 50
- condenses the treatment into just five days by doing 10 sessions a day.
In a single month-long study, 29 people with treatment-resistant depression were randomly assigned to receive SAINT or a dummy version. By the end of the month, 78% of the SAINT group had experienced complete remission compared to 7% in the sham group. Remarkably, this efficacy surpasses even electroconvulsive therapy, the current gold standard for treatment-resistant depression. SAINT treatment appeared safe and well tolerated, on par with standard TMS.
Many unknowns in the new TMS approach
Given its potential, the FDA has cleared Magnus Medical, a biomedical company working with Stanford, to market SAINT through a 510(k) pathway — a process that relies on the safety history of devices previously approved for TMS. However, many questions need to be answered before this new treatment can be widely adopted.
- Will the high rates of remission be sustained across various treatment sites and populations? Ideally, new treatment options are tested in larger multicenter randomized controlled trials before they reach the world.
- How long do the positive effects last? A small, short-term study cannot show this or suggest the best approach if depression returns after a person completes accelerated treatment.
- Are the side effects different from the standard TMS? While the adverse effects of the standard TMS are well established and generally well tolerated, it is not yet known whether the same is true for the SAINT protocol, given the low number of people who have tried it to date.
- Which components of the SAINT protocol have the greatest impact on its striking remission rates? Can high response rates be achieved with more accessible techniques? The SAINT protocol, as described, requires extensive expert planning using high-tech neuroimaging approaches that are unavailable in most parts of the country. Its implementation also requires dedicated equipment, personnel and space that could disrupt other clinical operations. Perhaps adjustments can be made to maintain the benefits while improving accessibility for a wider range of TMS providers and their patients.
Moving forward with a new treatment: shopper beware
Depression care is an area of great and continuing need in this country. Advances like the SAINT protocol hold enormous potential, but also many unknowns. With such excitement around the results of the new approach, it’s no surprise that clinics are springing up across the country offering similar expedited TMS services. But how strictly will these clinics adhere to all elements of the SAINT protocol? We don’t have those answers, and we can’t yet be sure that tracking all of the items will yield the same results in larger, long-term studies.
For now, most sites offering variations of this new treatment approach will not be covered by insurance. Expedited processing will occur at substantial cost while still being limited by many of the unknowns discussed above. Before moving forward, people seeking treatment for depression and their clinical teams will need to determine what level of uncertainty is best for them.
The SAINT Technique has the potential to transform the lives of millions of people with depression, but the recent study and its subsequent FDA clearance are only the first steps. Exactly how this approach fits in remains to be determined.