A neurosurgeon at the Medical University of South Carolina (Charleston) has reported positive results with a new neurosurgical procedure for treatment-resistant depression. A small study – just five patients – found that bilateral epidural prefrontal cortical stimulation (EpCS) was generally safe and provided significant improvement of depressive symptoms.

Seven months after implantation, patients experienced an average 54.9% improvement based on the Hamilton Rating Scare for Depression and 60.1% on the Inventory of Depressive Symptoms Self Report. Three patients reached remission and one had a minor complication that required removal of the implants.

"I came up with the idea because I've been researching brain stimulation for over a decade," Ziad Nahas, MD, director of the Mood Disorders Program at MUSC and medical director of the Brain Stimulation Laboratory, told Medical Device Daily. "We focused on these two regions because they are part of a larger brain network critical in regulating mood. Both play complementary roles integrating emotional and cognitive experiences and offer a distinct opportunity for targeted antidepressant treatments."

In a study published in Biological Psychology, Nahas and his team reported that five patients were implanted with EpCS over the anterior frontal poles and the lateral prefrontal cortex bilaterally. Four separate paddle leads were then connected to two small generators surgically implanted in the upper chest area of the patient. They then individualized the treatment parameters for each patient to maximize the long-term antidepressant effects. They relied in part on input from the patients who signaled positive mood changes when first stimulated in the operating room.

"In the OR, we tested for the first time the stimulation and showed that in the small group of patients, we had significant immediate changes in terms of reducing anxiety and sadness," Nahas said. "A couple of patients voiced an immediate feeling of increased attention and clarity. One patient had no reaction in the OR at all. But it was exciting as well as surprising that we could change emotions right there in the OR."

Only the sickest patients were included in this study, those who failed to respond to several antidepressant treatments, including medications, psychotherapy, transcranial magnetic stimulation, vagus nerve stimulation or electroconvulsive therapy.

Medtronic (Minneapolis) donated its SynergyPlus+ neurostimulation system for the experiments, although the company is taking no part in this study or Nahas' research.

The devices were set to periodically deliver electrical charges at intensities below the seizure threshold and they were never active at night.

One of the unique aspects of this application of cortical stimulation is that Nahas and team are using the stimulation intermittently and repeatedly, rather than continuously.

"The idea with this is that we would implant electrodes over areas involved in mood regulation and stimulate intermittently so we could, over time, improve depressive symptoms," he said. "By using repeated and intermittent stimulation, we could try to push the brain to adapt and change its function to have a better role at sustaining response. So one of the most critical elements in what we did, aside form the site targets, was that we also chose to go in not in a continuous mode of stimulation, but to got with intermittent cycles to not only bank on the immediate effect, but to help the brain choose to adapt to . . . a new homeostasis."

Nahas said this therapy is probably safer than deep brain stimulation because electrodes aren't inserted deep into brain tissue, which avoids any potential for brain damage.

Although the current study reports on seven-month data, Nahas has been following the patients for 1.5 years. He said that three out of the five patients had a recurrence of symptoms, but "It was fairly different from previous episodes. Their recurrence was short lived, whereas prior to having the implanted device, their average depressive episode lasted two-plus years."

He will continue to follow the patients indefinitely as he now seeks grant money to scale up for a larger trial.

The average battery life for the SynergyPlus+ runs between one and four years, depending on usage. Nahas said he'll advocate for replacement batteries down the road as needed, assuming these participants continue to reap benefits and remain depression free.

Lynn Yoffee; 770-361-4789
lynn.yoffee@ahcmedia.com