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Which brain area should deep brain stimulation target in order to improve treatment-resistant depression? Researchers may have found an answer. Image credit: artpartner-images/Getty Images.
  • About 30% of people with major depressive disorder (MDD) develop treatment-resistant depression.
  • Researchers from UTHealth Houston say deep brain stimulation applied to certain areas of the brain may help treat it.
  • The research team found that depression in 8 out of 10 treatment-resistant patients decreased by at least 50% after deep brain stimulation.

About 30% of people receiving care for major depressive disorder have treatment-resistant depression. Treatment-resistant depression occurs when a person does not respond to at least two different antidepressant medications.

Treatment options for this form of depression include additional medications, psychotherapy, and brain stimulation.

Now, a team of researchers from UTHealth Houston has found that delivering deep brain stimulation to the areas of the brain related to reward and motivation may help alleviate treatment-resistant depression.

This study recently appeared in the journal Molecular Psychiatry.

The World Health Organization (WHO) ranks depression as the most common illness in the world, affecting about 3.8% of the global population.

Major depressive disorder or clinical depression is a mood disorder that impacts a person’s daily life. Symptoms of depression include:

The treatment for depression normally includes medication, psychotherapy, or a combination of both. Medications for depression can include antidepressants, antipsychotics, and mood stabilizers.

If a person receiving treatment for depression does not respond to at least two different antidepressant medications, they may have treatment-resistant depression.

Current treatments for this include:

Deep brain stimulation is a neurosurgical treatment where electrodes are implanted into the brain. The electrodes send out electrical signals to the brain, helping to change and correct the way in which it operates.

Over 160,000 people globally have received deep brain stimulation treatment for both neurological and non-neurological issues.

Deep brain stimulation is commonly used to treat movement disorders such as Parkinson’s disease and dystonia. Researchers have also studied it as a potential treatment for treatment-resistant depression.

A systematic review of clinical outcomes published in 2014 found that 40-70% of people with treatment-resistant depression treated with deep brain stimulation showed an improvement of over 50% in their symptoms.

“Unfortunately, despite all resources we have to treat depression and even treatment-resistant depression, not all patients respond to them,” explained Dr. João de Quevedo, professor in the Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth Houston, and a co-author of the study.

“Invasive treatment strategies including deep brain stimulation come to address the unmet needs of this treatment-resistant depression subpopulation,” he added.

According to Dr. de Quevedo, the purpose of this research study was to show the efficacy of their surgical approach in improving depressive symptoms of people living with treatment-resistant depression.

“Despite [having] a rationale for choosing this specific target to land the electrodes, we need further evidence on which brain structures are activated downstream,” he told Medical News Today. “It generates a kind of roadmap of additional targets for treatment.”

During the study, Dr. de Quevedo and his team examined applying deep brain stimulation to the superolateral branch of the medial forebrain bundle in the brain. This area of the brain is related to reward and motivation.

Researchers applied deep brain stimulation to this particular area of the brain in 10 patients. Using PET scans conducted at 6 months and at 1 year following deep brain stimulation treatment, researchers found metabolic brain changes in 8 of the 10 patients, indicating a decrease in a patient’s markers of depression of at least 50%.

“We are paving the road that will lead us to large-scale clinical trials and therefore FDA approval,” Dr. de Quevedo stated. “Our proof-of-concept study is a starting point, not the end.”

Dr. Jean-Philippe Langevin, neurosurgeon and director of Restorative Neurosurgery and Deep Brain Stimulation Program for Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, said this new research is “exciting” as a potential new therapy for an area where there are currently not many options.

“The majority of patients with depression are going to get better with medication or psychotherapy, but there’s a small group that does not improve,” he explained to MNT.

“And so for those patients,” he added, “there’s not a whole lot of options out there. It was nice to see that in another line of evidence that perhaps neurosurgery could offer some help in the future.”

Dr. Langevin said clinicians are now discovering that patients with depression — and in particular, treatment-resistant depression — have anomalies or abnormal ways in which the brain is functioning or processing emotion.

“It could be that in those patients perhaps it’s a condition where the brain was wired that way, or sometimes it could be that events or medical conditions in life happen and change the way your brain is wired slightly and make it very difficult to get out of that feeling or those symptoms of depression,” he explained.

“In deep brain stimulation, we can alter the way the brain works in a more focal way. You can target those areas of the brain that are either too active or not active enough, and then switch their activity slightly or modulate it in a way that’s more conducive to proper emotional processing.”

– Dr. Jean-Philippe Langevin

When asked what he would like to see in future research, Dr. Langevin mentioned that while there has been other research examining the use of deep brain stimulation for treatment-resistant depression in different ways, he would like to see a more individualized approach.

“One patient may benefit from [deep brain stimulation] in one specific area versus another one and another area,” he noted. “That could explain why some patients [respond] in those trials, whereas other ones may not be responding as well.”

“In general, I think what we need is continuing to pursue the work with larger studies to prove whether or not we’re on the right track,” Dr. Langevin added.