A new method of brain stimulation designed by Stanford researchers to treat depression rapidly improved depressive symptoms in a small group of treatment-resistant patients who had suffered for decades with no relief, according to a study published in Brain.
This new method of high-dose transcranial magnetic stimulation uses rapid, repeated bursts of magnetic pulses to stimulate the brain.
“These are people who have been depressed most of their adult life and that’s how their life is, trying to find something that helps,” said Nolan Williams, MD, an instructor in psychiatry and behavioral science at Stanford and lead author of the study. “Nothing else has worked for this group of patients.”
The pilot study of six patients showed that after five days of intermittent sessions of treatment, patients reported their depression improved. The relief was temporary, lasting for about two weeks on average, but still groundbreaking because it was previously thought that only brain surgery could provide any form of relief for these types of patients, Williams said.
“If you failed multiple treatments plus ECT (electroconvulsive therapy) like these people have, the only thing found to work with any level of success is brain surgery,” he said. These patients had tried everything from antidepressants to ketamine infusions to the traditional (FDA-approved) form of repetitive transcranial magnetic stimulation (rTMS) to various forms of psychotherapy, Williams said.
The experimental therapy is an accelerated schedule of a new form of TMS called theta-burst stimulation. Like traditional rTMS which has been in use to treat depression since 2008, theta burst is able to treat patients with major depression but in a much more efficient way. Three minutes of theta-burst stimulation is equivalent to 40 minutes of traditional rTMS, the study said. To deliver the therapy, electricity travels through a coil, which generates a magnetic field. The coil is placed near the head of the patient, and the magnetic fields then induce pulses of small electric field changes in the brain. This then serves to increase or decrease the electrical firing in brain circuits.
In the traditional therapy, a patient will receive about 3,000 magnetic pulses per day over a 4-6 week period for a total of 90,000 pulses per treatment course. This new experimental therapy delivers 18,000 theta-burst pulses across a day in a patterned schedule over five days, the study said. TMS is a non-invasive procedure that can be delivered while a patient is reading a book or watching television, Williams said. No anesthesia or other drugs are used, and there is no autobiographical memory loss unlike the potential risk with electroconvulsive therapy.
For this pilot trial, therapy was delivered in 10-minute sessions with 50-minute intervals in between. Ten sessions were conducted per day for five consecutive days. Depression severity was measured immediately after the final session and then at two and four-week follow-ups. No adverse events were reported. A depression survey found a 76 percent reduction in symptoms after the final session.
Williams, who is director of Stanford’s Brain Stimulation Laboratory, said he has seen good results in patients treated with the traditional form of TMS therapy, but for it doesn’t work for everyone and, for many, it takes too long.
“We speculated maybe these patients were being under-dosed with the traditional form of TMS,” Williams said. For patients admitted to inpatient psychiatric care, the time of highest risk of suicide is within 30 days after the hospitalization. Getting better treatments to these patients faster would be lifesaving.
Williams said he has also seen much faster and longer lasting results when the accelerated treatment has been used for moderately severe depressed patients, with fewer past treatment failures. A new placebo-controlled trial is currently underway to test the new treatment on a much broader population of more moderately severe depressed participants.
“We want to get this method out there now though because these outcomes for severely ill patients have been so powerful,” Williams said. Williams and colleagues are applying for “compassionate use” of the new treatment, referring to the process of applying for government approval to use an experimental treatment when no other treatments are available.
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