Treatment quickly relieves severe depression in 90% of Stanford study participants

Artistic concept Magnetic brain stimulation

A new form of magnetic brain stimulation quickly relieved symptoms of severe depression in 90% of participants in a small study done by researchers at Stanford University School of Medicine.

The researchers are conducting a larger, double-blind study in which half of the participants receive incorrect treatment. Researchers are optimistic that the second study will be equally effective in treating people whose condition has not improved with medication, talk therapy, or other forms of electromagnetic stimulation.

The treatment is called Stanford Accelerated Intelligent Neuromodulation Therapy or SAINT. It is a form of transcranial magnetic stimulation approved by the Food and Drug Administration for the treatment of depression. The researchers reported that the therapy improves current FDA-approved protocols by increasing the number of magnetic impulses, accelerating the pace of treatment, and targeting the impulses according to individual neurological cycles.

Before the start of therapy, all 21 study participants were severely depressed after several diagnostic tests for depression. Thereafter, 19 of them scored in the non-depressive area. Although all participants had thoughts of suicide before the therapy, none of them reported having thoughts of suicide after the treatment. All 21 participants had previously experienced no improvements with medication, FDA-approved transcranial magnetic stimulation, or electro-seizure therapy.

The only side effects of the new therapy were fatigue and some discomfort during treatment, the study reported. The results will be published online today (April 6, 2020) in the American Journal of Psychiatry.

“There has never been a treatment for treatment-resistant depression that exceeded the 55% remission rate in open tests,” said Dr. Nolan Williams, assistant professor of psychiatry and behavioral science and lead author of the study. “Electrospasm therapy is the gold standard, but only has an average remission rate of 48% for treatment-resistant depression. Nobody expected such results. “

Calming of the brain chatter

When 60-year-old Deirdre Lehman woke up on the morning of June 30, 2018, she said she was hit by a “tsunami of darkness”. Lehman has struggled with bipolar disorders throughout her adult life, but her mood has been stable with medication and psychotherapy for 15 years.

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“There was constant chatter in my brain: it was my own voice that spoke about depression, agony, and hopelessness,” she said. “I said to my husband:” I’m going down and going towards suicide. “There didn’t seem to be any other option.”

Lehman’s psychiatrist had heard of the SAINT study and referred it to Stanford. After the researchers found the place in her brain that would benefit from stimulation, Lehman underwent the therapy.

“In the third round, the chatter started to subside,” she said. “For lunch I could look my husband in the eye. With each session the chatter became less and less until it was completely calm.

“It was the greatest peace that has been in my brain since I was 16 and that has taken the path to bipolar disorder.”

In transcranial magnetic stimulation, electrical currents from a magnetic coil on the scalp stimulate a region of the brain that is involved in depression. Treatment approved by the FDA requires sessions once a day for six weeks. Only about half of the patients who undergo this treatment improve and only about a third suffer from a remission due to depression.

Stanford researchers hypothesized that some modifications to transcranial magnetic stimulation could improve its effectiveness. Studies had shown that a stronger dose of 1,800 pulses per session instead of 600 would be more effective. The researchers were cautiously optimistic about the safety of the treatment, as this stimulation dose was used without harm in other forms of brain stimulation for neurological disorders such as Parkinson’s disease.

Other studies indicated that accelerating treatment would help relieve patients’ depression more quickly. With SAINT, the study participants underwent 10 sessions a day with 10-minute treatments with 50-minute breaks in between. After a day of therapy, Lehman’s mood showed that she was no longer depressed. For other participants, it took up to five days. On average, three days of therapy were sufficient to relieve the participants of depression.

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“The fewer treatment-resistant participants are, the longer the treatment will take,” said postdoctoral researcher Eleanor Cole, Ph.D., a lead author in the study.

Strengthen a weak connection

The researchers also suspected that more accurate stimulation targeting would improve treatment effectiveness. With transcranial magnetic stimulation, the treatment targets the location where most people’s dorsolateral prefrontal cortex is located. This region regulates executive functions such as the selection of appropriate reminders and the prevention of inappropriate answers.

For SAINT, the researchers used magnetic resonance imaging of brain activity to locate not only the dorsolateral prefrontal cortex, but also a specific subregion in it. They identified the sub-region in each participant who was related to the subgenic cingulate, a part of the brain that is overactive in people with depression.

In people with depression, the link between the two regions is weak and the subgenural cingulate becomes overactive, said Keith Sudheimer, Ph.D., clinical assistant professor of psychiatry and lead author of the study. Stimulating the sub-region of the dorsolateral prefrontal cortex reduces activity in the subgenural cingulate, he said.

To test safety, the researchers assessed participants’ cognitive functions before and after treatment. They found no negative side effects; In fact, they found that participants’ ability to switch between mental tasks and solve problems had improved – a typical result for people who are no longer depressed.

One month after therapy, 60% of the participants were still in remission from depression. Follow-up studies are ongoing to determine the duration of the antidepressant effects.

The researchers plan to investigate the effectiveness of SAINT in other diseases such as obsessive-compulsive disorder, addiction and autism spectrum disorders.

“Elastic and stable”

The depression that Lehman woke up almost two years ago was the worst episode she had ever experienced. Today, she said, be happy and calm.

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Since her SAINT treatment, she has a bachelor’s degree from the University of California at Santa Barbara. She had dropped out as a young woman when her bipolar symptoms overwhelmed her studies.

“I’ve always cried over the smallest thing,” she said. “But if bad things happen now, I’m just resilient and stable. I am in a much more peaceful state and can enjoy the positive things in life with the energy to get things done. “

Reference: April 6, 2020, American Journal of Psychiatry.

Graduate students Katy Stimpson and Brandon Bentzley, MD, Ph.D., a medical assistant in psychiatry and behavioral sciences, are also primary authors.

Other Stanford co-authors include former laboratory manager Merve Gulser; PhD students Kirsten Cherian, Elizabeth Choi, Haley Aaron and Austin Guerra; Flint Espil, Ph.D., clinical assistant professor of psychiatry and behavioral science; Research coordinators Claudia Tischler, Romina Nejad and Heather Pankow; Medical student Jaspreet Pannu; Postdocs Xiaoqian Xiao, James Bishop, John Coetze and Angela Phillips; Hugh Solvason, MD, Ph.D., clinical professor of psychiatry and behavioral science; Research Director Jessica Hawkins; Booil Jo, Ph.D., associate professor of psychiatry and behavioral science; Kristin Raj, MD, clinical assistant professor of psychiatry and behavioral science; Charles DeBattista, MD, professor of psychiatry and behavioral science; Jennifer Keller, Ph.D., Associate Clinical Professor of Psychiatry and Behavioral Sciences; and Alan Schatzberg, MD, professor of psychiatry and behavioral science.

The research was funded by Charles R. Schwab, the Marshall and Dee Ann Payne Fund, the Lehman Family Neuromodulation Research Fund, the Still Charitable Fund, the Avy L. and Robert L. Miller Foundation, the Stanford Psychiatry Chairman’s Small Grant, the Stanford , supports CNI Innovation Award, the National Institutes of Health (grants T32035165 and UL1TR001085), the Stanford Medical Scholars Research Fellowship, the NARSAD Young Investigator Award and the Gordie Brookstone Fund.

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