4 in 5 May Respond Remarkably Well to New Experimental Depression Treatment

A new method of brain stimulation treatment from Stanford University led to unheard-of remission rates in patients with moderate to severe depression.

“We’ve just gotten used to something working for 25% of people and getting really excited about that,” Nolan R. Williams, MD, senior study author and director of the Stanford Brain Stimulation Lab, told Verywell.

But now, Stanford neuromodulation therapy (SNT) seems to be working for a much higher percentage of people. This recent study shows about 79% of patients went into remission within days of treatment. The remissions also lasted months, and with few side effects.

The patients had not previously found much depression relief from other standard treatments like antidepressant medication or psychotherapy.

SNT is basically an updated form of transcranial magnetic stimulation—a therapy that is already used to treat depression. This new treatment, however, individualizes stimulation to a patient’s neurobiology.

“I think the difference here is that we’ve tapped into this central biology of the condition,” Williams said. “That’s the reason why we’re seeing much higher numbers.”

The findings were published in The American Journal of Psychiatry in late October.

How Stanford Neuromodulation Therapy Works

Brain stimulation therapy is not a new treatment.

Treatments like electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation are already approved by the Food and Drug Administration (FDA) and used to treat conditions like depression.

However, SNT is more similar to another FDA-approved therapy, repetitive transcranial magnetic stimulation (rTMS)—a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain. When patients receive rTMS, an electromagnetic coil is placed against the forehead, delivering painless magnetic pulses that stimulate brain regions thought to have under-regulated activity in depression.

Since only a portion of patients (about a third) go into remission with rTMS, researchers at Stanford wanted to see if they could make the treatment more effective by individualizing it and upping the intensity.

First, the researchers used brain imaging techniques to tailor treatment to each participant. Seeing the brain through MRI helped researchers locate the exact subregion in the dorsolateral prefrontal cortex that was most under-regulated with the subgenual cingulate. The two regions are thought to play a role in depression, and a dysregulated connection between the two is related to depressed mood and loss of pleasure.

At the same time, rTMS is thought to strengthen the connection between the two areas. By individualizing the region that received stimulation, the researchers hoped to make the treatment more effective for each participant.

In addition to tailoring stimulation to each person, researchers also increased the number of pulses per session by three times—from the standard of 600 to 1,800. This high pulse rate has been used safely in treating neurological disorders such as Parkinson’s disease.

Lastly, the third change had to do with timing and frequency. Instead of the usual one treatment per day, researchers gave participants ten 10-minute treatments per day, with 50-minute breaks in between.

Almost 80% Experienced Remission

Williams and colleagues enrolled 29 people with severe, treatment-resistant depression. They were treated in a controlled lab setting, all wearing noise-canceling earphones. Neither the researcher administering the procedure nor the participant knew whether they were undergoing actual SNT or placebo.

About half of the participants received SNT, while 15 received a placebo. The 29 participants ranged in age from 22 to 80, and had on average been dealing with depression for nine years. All individuals hadn’t received much relief via medication, psychotherapy, or other life changes, but those who were on medication were told to maintain their regular dosage.

Four weeks after the treatment’s close, researchers measured participants’ depression scores using the Montgomery-Åsberg Depression Rating Scale (MADRS). Twelve of the 14 participants who had received SNT improved, with 11 meeting FDA criteria for remission. In the placebo group, only two of the 15 met the criteria for remission.

“We’ve figured out that you have to find the right spot for each person, and it’s different for everybody,” Williams said. After that comes correct stimulation and dosing, which SNT updated by intensifying pulse and treatment frequency.

Although the remission rate is remarkable, the study size was still very small. Tailoring the technique to a larger and more diverse patient population would be necessary to say how well and how long SNT’s effects last.

Another Tool in the Toolbox

About a third of patients with depression do not benefit from traditional treatments like medication and psychotherapy. This has led the way to the increasing use of brain stimulation therapies, which researchers like Williams and colleagues seek to continue improving.

“I think there’s a lot more to do,” Williams said. That is, just because almost 80% went into remission within a month after treatment doesn’t mean they’ll be in remission forever.

“So we’ve got to figure out a way to keep everyone well, so it’s truly 80% forever,” Williams added.

Extending the near-immediate effects of SNT could include pairing it with other treatments, such as drugs or lifestyle changes. “Some of those patients relapsed quicker,” Williams said. “We have to find a way to keep them well.”

There are already many tools to treat depression, such as antidepressant medication, psychotherapy, and other brain stimulation treatments, but people sometimes don’t get the care they need. For example, more than 75% of people in low- and middle-income countries receive no treatment. In places where treatment is more accessible, factors like stigma could lead to misdiagnosis and/or prescription treatments that don't work for the individual.

Antidepressants can also take a long time to kick in, dragging out the treatment. Sometimes people spend months to years searching for the best antidepressant for them.

But SNT’s rapid effects, still requiring further research, might speed up that treatment process and add another tool to the toolbox. If it is found to be safe and effective for people with treatment-resistant depression, it could be, as the researchers said, a game-changer.