A new neurosurgical procedure may prove helpful for patients with treatment-resistant depression. Bilateral epidural prefrontal cortical stimulation (EpCS) was found generally safe and provided significant improvement of depressive symptoms in a small group of patients, according to lead researcher Ziad Nahas, M.D. at the Medical University of South Carolina (MUSC). Science Daily reports that treatment-resistant depression is a recurrent psychiatric illness and a leading cause of premature morality due to suicide and associated medical conditions. In the U.S., more than 3.2 million patients are diagnosed with treatment-resistant depression. Typically, patients have tried several medications and treatments without success or improvement. EpCS targets electrical stimulation to the anterior frontal poles and the lateral prefrontal cortex. \u201cWe focused on these two regions because they are part of a larger brain networks critical in regulating mood. Both play complementary roles integrating emotional and cognitive experiences and offer a distinct opportunity for targeted antidepressant treatments,\u201d said Dr. Nahas, an associate professor of psychiatry, physiology, and neuroscience and director of the Mood Disorders Program at MUSC. \u201cCortical stimulation has several advantages provided that it shows efficacy in treating depression. It is reversible, non-destructive and potentially safer than other forms of invasive brain stimulation since the stimulating paddles don\u2019t come in direct contact with the brain,\u201d Nahas continued. His team included MUSC neurosurgeon Istvan Takacs, M.D. and MUSC anesthesiologist Scott Reeves, M.D. 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. The researchers individualized the treatment parameters for each patient to maximize the long-term anti-depressant effects. They relied in part on input from the patients themselves who signaled positive mood changes when first stimulated. In general, their devices were set to periodically deliver electrical charges at intensities below the seizure threshold. The devices were never active at night. Only patients who failed to respond to several antidepressant treatments\u2014including medications, psychotherapy, transcranial magnetic stimulation, vagus nerve stimulation, or electroconvulsive therapy\u2014were included in the study. Patients were closely followed after the surgical implant and evaluated regularly using standard clinical ratings. After seven months, the average improvement was 54.9 percent based on the Hamilton Rating Scare for Depression and 60.1 percent on the Inventory of Depressive Symptoms Self Report. Three of the patients reached remission. One patient experienced a scalp infection that required removing the implants over the left hemisphere. \u201cThese preliminary results are encouraging but not definitive,\u201d said Dr. Nahas. \u201cNow that we have a proof of concept, we should aim at studying bilateral EpCS in larger placebo-controlled studies,\u201d he continued. \u201cThe more sophisticated functions are on the surface of the brain\u201d said Takacs. \u201cWe are trying to change the climate within the prefrontal cortex so it could exert more adaptive governance of deeper brain regions,\u201d he added. The study was funded by the National Alliance of Research in Schizophrenia and Affective Disorders (NARSAD), the brain and behavior research fund.