Stanford’s SAINT Study: a TMS Breakthrough for Depression?
Image: Freedom by Daniel Reche (CC0)
Synopsis: It has been definitively proven that transcranial magnetic stimulation (TMS) is an effective treatment for treatment-resistant depression. However, there are aspects to TMS that make it harder to access, such as daily treatment for weeks and cost, especially when outcomes from the treatment vary. The researchers in the Stanford SAINT study achieved better results in a shorter time, getting 90.5% of severely depressed patients to full freedom from depression in just one week of treatment.
BY LEN LANTZ, MD / 7.19.20; No. 29 / 8 min read
Disclaimer: Yes, I am a physician, but I’m not your doctor, and this article does not create a doctor-patient relationship. This article is for educational purposes and should not be seen as medical advice. You should consult with your physician before you rely on this information. This post might also contain affiliate links. Please click this LINK for the full disclaimer.
What are the current treatments for depression?
Psychotherapy is – and will always be – the foundation of treatment for depression. Antidepressants are often the next step in treatment, though some people with depression instead choose to try antidepressant medications first and start psychotherapy later if they are not seeing a good response to medication.
The causes of depression are often complex, as they can come from many different directions. It takes skill and thoroughness to sort out how to help people to become free (achieve remission) of depression. A significant percentage of people get temporarily and partially better, only to fall back into depression feeling more demoralized than when they started.
In my heart, I also feel demoralized when the people I treat with antidepressants are not getting better and staying better. Make no mistake: antidepressants can and do work. I regularly and successfully prescribe medications for many depressed patients. You can learn more details about depression in my article, “The Most Important New Findings in Depression.”
However, there is a new treatment for depression that is an absolute game-changer. It’s called Transcranial Magnetic Stimulation, or TMS Therapy. It does not require psychiatric medication to work. It works when traditional treatments such as medication and therapy are failing. TMS Therapy is FDA-approved and scientific research proves that it works. It uses high-intensity magnetic pulses to stimulate the frontal lobe of the brain over time to alleviate depression.
I was so blown away by the results from scientific research that in 2017, I changed my entire medical practice (moved office buildings, added staff, purchased a TMS machine) before I treated my first patient with TMS Therapy. It was a huge risk and it was well worth it!
How does TMS compare to other treatments for refractory depression?
Currently, ECT (electroconvulsive therapy) remains the gold standard for treatment-resistant depression. There are several challenges to people accessing ECT, one of which is the cost. ECT costs roughly twice as much as TMS and it is not available in every community, so travel costs and time can be considerable. Also, there is significant stigma around ECT as it has been portrayed by Hollywood as barbaric and abusive, which it is not. ECT for depression has saved thousands of lives, however, given the above considerations, many people refuse to pursue it. A comparison of ECT and TMS shows:
ECT
Anesthesia
No driving
Electricity-induced seizure
Temporary or permanent memory loss
Unable to work day of treatment
Treatment time = hours
TMS
No anesthesia
Able to drive to/from appointment
No seizure
No memory impairment
Able to return to work after treatment
Treatment time = 20 minutes
TMS really is the best new FDA-approved treatment for treatment-resistant depression. I’m guessing you’ve heard of ketamine as a new treatment for depression. I think the research is clear that IV ketamine, and possibly the esketamine nasal spray, are faster at addressing suicidality. However, TMS works better as a stand-alone treatment for depression. Ketamine has significant systemic side effects, but TMS doesn’t have any – not one.
After therapy and antidepressant medications, TMS has quickly become the next step in treatment. TMS appears to be a 3rd level of treatment, which many patients prefer as it’s less invasive than ECT. You can learn more details about TMS in my article, “Transcranial Magnetic Stimulation (TMS) – the Best New Depression Treatment.”
What is currently available in TMS Therapy?
Most TMS machines use a non-proprietary copper coil, called a figure-8 coil, to generate magnetic pulses to stimulate the brain (often referred to as rTMS). These machines are effective at treating depression and their results are improved when precision targeting, called neuronavigation, is used to stimulate the target area, which is the dorsolateral prefrontal cortex (DLPFC). Unfortunately, most rTMS providers do not use neuronavigation, due to cost and increased expense, and because the figure-8 coil stimulates a smaller area of the brain, they may miss the DLPFC.
We have known since 2001 (Herwig, et al. Biol Psychiatry, 2001) – 7 years before the FDA even approved TMS – that the figure-8 machines without neuronavigation miss the DLPFC up to 2/3 of the time. Without neuronavigation, a doctor using a figure-8 machine is simply relying on measurements and calculations on the surface of someone’s head.
A BrainsWay TMS machine does not miss the DLPFC because its proprietary coil stimulates deeper and over a larger area (often referred to as dTMS). When the BrainsWay machine and figure-8 coil were compared in a head-to-head trial, the BrainsWay machine had better outcomes (Filipcic, et al. Journal of Psychiatric Research. 2019).
Recently, a new treatment protocol using rTMS figure-8 coils greatly shortened the treatment window (often referred to as intermittent theta burst stimulation or iTBS). The critical iTBS study compared a 3-minute iTBS treatment to a standard 37.5-minute rTMS treatment and found that the outcomes were the same.
What are some limitations to accessing TMS Therapy?
One of the barriers to accessing TMS is the cost. Current treatment protocols for TMS involve 36 treatments over 6-9 weeks. Brainsway was approved by the FDA with a 44-treatment protocol. Any medical intervention that takes 36 treatments is going to be costly due to the multiplier effect (36 x $100 = $3,600; 36 x $200 = $7,200; 36 x $300 = $10,800; etc.). Also, if a medical treatment will take a person to their individual out-of-pocket maximum limit for their health insurance, that person might want a guarantee that the treatment will work 100% of the time, however, the best TMS outcomes to date have a remission rate at around 50%.
Because current treatment protocols involve daily treatment, TMS works best if you have it in your hometown. Traveling more than an hour one-way to a daily TMS treatment is very difficult on a person’s schedule. It is even more difficult for people who live in rural areas as travel to medical care often takes even longer.
Additional limitations include the delay by the FDA to approve TMS for other depression indications. Currently, TMS is only approved to treat adult depressive illnesses that fall under Major Depressive Disorder. TMS has also been shown to be safe and effective in the treatment of pediatric depression, bipolar depression and maintenance treatment (preventing depression from recurring). Because the FDA has not provided approval for those additional indications, health insurance companies refuse to pay for these treatments, even though they are effective.
What did Stanford do in the SAINT study?
As you might have guessed, there is a bit of an arms race with TMS machines and protocols. The newest edition is the “Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression” by Dr. Nolan Williams and his research team (Cole, et al. Am J Psychiatry. 2020). This is one of the most exciting studies in TMS as it achieved a 90.5% remission rate. It was a small study without sham (placebo) control of 22 patients with major depression (2 patients had Bipolar II disorder with a > 1-year current episode of depression). The Young Mania Rating Scale was completed each day to prove that the researchers weren’t just temporarily making everybody hypomanic.
Treatment occurred 10 times per day for 5 days and then treatment was stopped. The patients were followed for 5 weeks to measure whether or not the improvement was sustained. The researchers ran a modified iTBS protocol that lasted 10 minutes, which was longer than the previous 3-minute and 6-minute iTBS protocols. They also delivered 10 treatments per day, not one as is the standard. Patients received a lot more – five times more – stimulations than the iTBS protocol approved by the FDA. The researchers also stimulated the brain at a lower intensity than other protocols. They used functional MRI (fMRI) to individually target the left DLPFC of each patient and used neuronavigation to enact precision targeting.
What are takeaways from the SAINT study?
The SAINT study protocol is not ready for widespread clinical application. This is a small study and needs to be replicated and we need larger studies. If this study holds up, it could be a complete game-changer in terms of how all TMS is delivered.
The SAINT study is an open study. We need to compare active treatment to sham (placebo). But sham will probably not result in the significant, sustained improvement observed in the SAINT study. Treatment-resistant patients are less likely to respond to a placebo (Razza, et al. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018).
(Note to reader: Please see my article, “A New Kind of TMS for Depression: SAINT Becomes Stanford Neuromodulation Therapy (SNT)” for newly released research on SAINT.)
The science looks sound. I believe the replication study will probably show similar results.
fMRI use may make it harder to replicate. An fMRI machine costs about half a million to 3 million dollars, depending on the resolution. Even though fMRI can technically be run on a regular MRI machine, quality results often require a higher-level (3 tesla) MRI machine with a trained radiologist and a team to crunch the data.
The TMS treatment protocol matters. One hypothesis of the SAINT study is that conventional TMS is essentially underdosing some patients. The SAINT treatment only lasted 5 days, not 9 weeks. It dosed at a lower power of 90% of the patient’s motor threshold (rMT). It provided treatments 10 times per day, not one time per day. And it delivered 5 times more total stimulations than the FDA-approved iTBS protocol.
We don’t know the duration of remission of the SAINT study past 5 weeks. Other TMS research shows a typical duration of benefit of at least 1 year (Dunner, et al. J Clin Psychiatry. 2014). Will a patient’s remission “stick” after 5 days of treatment under SAINT?
Targeting matters. The SAINT study had high-level targeting of the left DLPFC.
What could the SAINT study mean for rural states?
If the SAINT protocol is replicated and adopted across the US, it could really help rural, frontier states like Montana. Farmers and ranchers in Montana cannot travel to Helena every day for 6 to 9 weeks for a traditional treatment protocol. The distances between people and medical care in Montana are substantial. Montana has only a million people, but our land area is huge. The distance across the state from corner to corner is equal to the distance between Chicago and Washington DC. If the SAINT protocol holds up, it could be transformative for states like Montana, which has one of the highest suicide rates in the nation.
Imagine having access to this treatment
TMS treatment already is changing – and saving – the lives of people with treatment-resistant depression. The SAINT study gives more hope to those who have been suffering in despair. If the SAINT study is replicated, it will show that TMS can be more effective even than ECT and may become the new gold standard in treating refractory depression. Even with existing treatment protocols, I have witnessed TMS help people achieve full freedom from depression even when they have co-occurring anxiety and decades of depression. Imagine a future where 5 days of intense treatment could reverse decades of depression. It’s exciting that a new TMS treatment protocol could nearly double the chances of successful treatment. Time will tell if this study will hold up. If it does, it will be transformative for our families and communities.
For further reading, check out:
Len’s article, “A New Kind of TMS for Depression: SAINT Becomes Stanford Neuromodulation Therapy (SNT)”
Len’s article “The Most Important New Findings in Depression”
Len’s article “Transcranial Magnetic Stimulation (TMS) – the Best New Depression Treatment”
Transcranial Magnetic Stimulation: Clinical Applications for Psychiatric Practice by Drs. Bermudes, Lanocha and Janicak
Network Neuroscience by Dr. Frohlich
Please follow us on Google News
It’s easy to follow us on Google News! Click this LINK to our FAQ page to learn how.
