A new clinical trial has tested the ability of a little-studied, noninvasive brain stimulation technique to treat the symptoms of major depression. The results, so far, have been more than promising.

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A different type of electrical brain stimulation has shown much promise for the treatment of depression.

Researchers from the University of North Carolina (UNC) School of Medicine in Chapel Hill have recently conducted a double-blind pilot clinical study testing a type of electrical brain stimulation therapy called "transcranial alternating current stimulation" (tACS) in people with major depression.

In double-blind studies, neither the participants nor the scientists who administer the treatment know who is set to receive which intervention.

This approach ensures added objectivity, which provides more reliable results.

The UNC researchers who conducted this pilot trial were interested in tACS as a therapy for depression and potentially other mental health conditions. They recognized it as a little-studied, more patient-friendly form of electrical brain stimulation.

Electrical brain stimulation does not constitute a new approach in the treatment of depression, but experts usually turn to transcranial direct stimulation (tDCS), which sends low direct electrical currents into the nervous system through electrodes that attach to a person's head.

Although this type of therapy has shown some promise, the team from UNC notes that the technique is not consistently effective. That is why the researchers decided to try testing tACS instead.

Rather than sending a steady flow of electrical current into the brain like tDCS, tACS can instead tackle a person's alpha oscillations, which are brain waves with a frequency of 8–12 Hertz. Specialists can measure these waves using an electroencephalogram.

'A first-of-its-kind study'

These brain waves, the researchers explain, grow in intensity when a person daydreams, meditates, or concentrates on a specific idea — that is, when the brain is entirely focused and shuts out distracting stimuli.

In people with major depressive disorder, alpha oscillations are more asymmetrical, meaning that they are much more active in one part of the brain — the left frontal cortex — than in the other.

In the new study, the findings of which now appear in the journal Translational Psychiatry, the researchers tested the effect of tACS on these oscillations with the ultimate aim of verifying whether the novel approach could improve symptoms of major depression.

"We conducted a small study of 32 people because this sort of approach had never been done before," notes the study's senior author Flavio Frohlich, Ph.D. "It's important to note that this is a first-of-its-kind study," he emphasizes.

Each of the 32 participants had already received a diagnosis of major depression, but the researchers also assessed symptom severity at baseline using the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard tool for evaluating depression.

During the study, the investigators split the cohort into three groups:

  • the first group received a placebo electrical stimulation that mimicked the sensation of the treatment
  • the second group received 40-Hertz tACS brain stimulation, which falls outside the range that can act on alpha oscillations
  • the third group, which was the main experimental group, received the proper treatment, which consisted of 10-Hertz tACS electrical currents that targeted individual alpha oscillation patterns with the goal of rebalancing them

'Now we can fine-tune our approach'

Every participant received their assigned therapy during a 40-minute session on each of 5 consecutive days. The researchers assessed the participants on the MADRS scale immediately after the 5-day intervention and at 2 and 4 weeks after the trial to gauge the therapy's effects.

Frohlich and team found that the people in the main experimental group, who had received 10-Hertz tACS stimulation, did indeed have an equalizing decrease in the brain wave oscillations in the left frontal cortex.

At the 4-week mark, there was no statistically significant improvement in depression symptoms in this group compared with the other two groups.

However, the data that the team collected 2 weeks after the end of the clinical study told a completely different story. At this follow-up point, 77.8 percent of the participants in the experimental group saw a reduction in depression symptoms of at least 50 percent compared with their situation at baseline.

This positive effect, the researchers note, was significantly higher in the main therapy group than it was in participants from the other two groups.

"When we started this research with computer simulations and preclinical studies, it was unclear if we would see an effect in people days after tACS treatment — let alone if tACS could become a treatment for psychiatric illnesses," says Frohlich.

"It was unclear what would happen if we treated people several days in a row or what effect we might see weeks later," he continues, adding that "the fact that we've seen such positive results from this study gives me confidence our approach could help many people with depression."

"Now that we've documented how this kind of tACS can reduce depression symptoms, we can fine-tune our approach to help many people in a relatively inexpensive, noninvasive way."

Flavio Frohlich

Currently, Frohlich and team are looking for participants for two follow-up studies further investigating the best uses of tACS therapy.