Depression is a leading cause of disability worldwide.
The National Institute of Mental Health estimate that 17.3 million adults experienced an episode of major depression in 2017 in the United States alone.
Suicidal thoughts, sometimes known as “suicidal ideation,” are common among people with major depression or bipolar disorder.
Antidepressant drugs can relieve depressive symptoms, including suicidal ideation, but they take several weeks to start working.
Scientists, therefore, see developing new treatments that are not only safe and effective but also fast-acting as a priority.
Ketamine and electroconvulsive therapy (ECT) are two proven therapies for the rapid treatment of suicidal ideation. However, some experts have concerns about the side effects associated with these treatments.
In addition, stigma has grown around the use of ECT, which means that people do not often use it.
To address the need for a fast-acting, effective treatment for depression, researchers at Stanford University School of Medicine, CA, have developed a new form of repetitive transcranial magnetic stimulation (rTMS).
They have dubbed their new treatment Stanford Accelerated Intelligent Neuromodulation Therapy, or SAINT.
In a small, preliminary study published online in The American Journal of Psychiatry, SAINT rapidly resolved symptoms of depression in 90% of patients.
However, it is worth noting that the trial was “open label,” meaning both participants and researchers were aware of the nature of the treatment. There was also no control group to account for the placebo effect.
Nonetheless, the high success rate was unprecedented even for an open label study, according to the researchers.
“There’s never been a therapy for treatment-resistant depression that’s broken 55% remission rates in open-label testing,” says Nolan Williams, MD, who was a senior author of the study.
“Electroconvulsive therapy is thought to be the gold standard, but it has only an average 48% remission rate in treatment-resistant depression. No one expected these kinds of results.”
Crucially, SAINT appeared to eliminate suicidal thoughts rapidly in all the patients.
The only adverse effects reported were fatigue and some discomfort during the treatment.
In 2008, the Food and Drug Administration (FDA) approved rTMS for people with treatment-resistant depression.
The technique involves sending electric current pulses through a magnetic coil placed on the scalp over a brain region called the left dorsolateral prefrontal cortex (L-DLPFC).
The L-DLPFC is responsible for executive functions, such as attention, working memory, and decision-making.
The magnetic field generated by rTMS excites nerve cells in the L-DLPFC, which, over time, strengthens the synapses that connect them. Stronger synapses are better at transmitting nerve signals.
Neuroscientists believe this is how the brain learns new ways of thinking and behaving, rewiring itself according to the principle that “nerves that fire together, wire together.”
Scientists think that the antidepressant effects of rTMS are the result of strengthened connections and stronger activity in the L-DLPFC, which in turn inhibits activity in another part of the brain involved in emotions.
Several studies have implicated overactivity in the subgenual anterior cingulate cortex (sgACC) in major depression and feelings of sadness.
Existing forms of rTMS, which involve daily stimulation sessions for 6 weeks, relieve symptoms of depression in around half of all patients.
Around a third of patients who receive regular rTMS achieve “remission.” This means that they no longer meet the diagnosis of depression according to standard assessment questionnaires.
The Stanford researchers theorized that they could achieve better results more quickly by increasing the intensity of magnetic stimulation and shortening the treatment schedule to 5 consecutive days.
The schedule for SAINT involves ten 10-minute sessions per day with 50-minute intervals between them.
The researchers also targeted the magnetic pulses more precisely.
A previous study had shown that the success of rTMS depends on the degree of “anti-correlation” between activity in the region of the L-DLPFC being stimulated and activity in the sgACC.
So the Stanford scientists used functional magnetic resonance imaging (fMRI) to identify the precise area within the L-DLPFC of each patient’s brain that had the strongest inhibitory effect on the sgACC.
All 21 participants had failed to respond to several other treatments, including antidepressant drugs, ECT, and conventional rTMS.
After completing the new therapy, however, researchers found that 19 (90%) of the participants were in remission.
Although all the participants had been experiencing suicidal thoughts before undergoing treatment, none reported having them after SAINT.
One month after the therapy finished, 60% of participants were still free from depression.
In their paper, the scientists conclude:
“The efficacy of SAINT at treating suicidal ideation and the short duration of the protocol suggest SAINT could provide a means of rapidly ensuring the safety of suicidal patients.”
They are now conducting a more significant, double-blind trial in which half of the participants will receive sham rTMS.
This means neither the scientists nor the participants will know whether the magnetic coil is switched on.
The scientists also plan to investigate whether SAINT works in other conditions, such as obsessive-compulsive disorder (OCD), addiction, and autism spectrum disorders.
