Intensifying a standard form of brain stimulation may bring relief to people with hard-to-treat depression, a preliminary study suggests.
The study involved just 21 patients, but the treatment sent 90% into remission within a few days. That's a success rate that has never been seen in early testing of other therapies for severe depression, the researchers said.
The therapy involves transcranial magnetic stimulation (TMS), where a magnetic coil is placed at the scalp to non-invasively deliver electrical pulses to a brain region involved in depression. In the United States, TMS is an approved option for depression that does not respond to standard antidepressant medication.
Normally, TMS is done once a day, over six weeks.
That conventional approach can help, but only about one-third of patients see their symptoms go into remission, said Dr. Nolan Williams, a senior researcher on the new study.
"So we've been thinking: How can we make it better?" said Williams, an assistant professor of psychiatry at Stanford University School of Medicine in California.
Based on prior research, he and his colleagues devised a new protocol for delivering TMS. One change was to intensify the treatment: Patients received more electrical pulses at each session, and the sessions were consolidated into 10 per day, over five consecutive days.
The researchers also aimed to individualize the target. Conventional TMS stimulates cells in a brain region called the dorsolateral prefrontal cortex, which regulates broad functions like selecting appropriate memories and suppressing inappropriate responses.
Here, patients had MRI scans to pinpoint targets within the dorsolateral prefrontal cortex that showed a relationship with the subgenual cingulate. That's a brain structure that tends to be overactive in people with major depression.
Stimulating those target areas is thought to dampen activity in the subgenual cingulate.
Of the 21 patients treated, 19 saw their symptoms go into remission. On average, it took about three days, the researchers reported. The findings were published online April 6 in the American Journal of Psychiatry.
One of those patients was Deirdre Lehman. The 60-year-old had struggled with bipolar disorder most of her life, but had been stable for about 15 years on medication and talk therapy. Then one morning in 2018, she woke to what she described as a "tsunami of darkness."
Fearful that she was heading toward suicide, she saw her psychiatrist, who referred her to the Stanford study. After day one of therapy, the "chatter" in her head had quieted, Lehman said in a statement from the university.
"These are promising findings," said Dr. Jeffrey Borenstein, president of the Brain & Behavior Research Foundation in New York City.
But Borenstein, who was not involved in the research, had a big caveat: This was an early, "open-label" study, meaning the researchers and patients all knew that the real treatment was being delivered.
That means it lacked a comparison group of patients who received a "sham" version of TMS. So, Borenstein explained, it's not possible to tell exactly how effective the new protocol is: Some patients might have improved due to the well-known "placebo effect."
To get more-definitive answers, the Stanford team is running a larger trial, in which half the patients are randomly assigned to a placebo group.
Williams said there are reasons to be optimistic: This study's 90% remission rate has never been seen in open-label studies of other therapies for treatment-resistant depression. None has done better than 55%, he said.
If the larger trial confirms the treatment works, Borenstein said, other questions to answer include: How long will the benefits last? Will they be maintained after repeat treatments?
In this study, the improvements did wane for some. Sixty percent of patients remained in remission after one month, while 70% were still showing some response.
As for safety, the only side effects were fatigue and discomfort during the treatment, the researchers said. They also tested patients' memory and thinking skills before and after the therapy, and found no ill effects.
In general, Williams noted, TMS does carry a risk of seizure — a roughly one in 30,000 chance.
If the new TMS approach pans out, Williams pointed to one potential use: helping people who are hospitalized for severe depression. Research shows that for those patients, the risk of suicide is highest soon after discharge.
So an effective therapy that can be delivered during a hospital stay could make an important difference, Williams said.