Deep Brain Stimulation for Treatment-Resistant Depression

Helen Mayberg, M.D.

Emory University School of Medicine, Atlanta, GA

Grant Program:

Clinical Neuroscience Research

Funded in:

December 2006, for 3 years

Funding Amount:

$400,000

Lay Summary

Deep Brain Stimulation for Treatment-Resistant Depression

Dana funding will help support a study of deep brain stimulation (DBS) in patients with severe depression whose symptoms are not alleviated by conventional therapies. The initial DBS clinical investigation by Dr. Mayberg and colleagues at the University of Toronto provided striking evidence of improvement in four of six patients with intractable depression. The expanded research by Dr. Mayberg and colleagues at Emory will involve an additional 20 patients and will explore the brain processes that result in depression and how DBS affects them. These studies build upon Dr. Mayberg’s groundbreaking Dana–funded PET imaging research, which provided evidence that depression involves multiple cortical circuits in a brain region called Cg25.

Dana funds support the psychiatric screening and recruitment of patients, their clinical management and assessment, and, data analyses to correlate patients’ clinical conditions with the brain imaging and EEG studies. Co-funding from the Stanley and Woodruff Foundations support the surgical and hospitalization costs and studies of brain processes involved.

Abstract

Deep Brain Stimulation for Treatment-Resistant Depression

Treatment-resistant depression (TRD) is a severely disabling disorder with limited treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Current research suggests that depression may result from abnormal function within neural networks involved in mood regulation. Neuroimaging studies further identify the subgenual cingulate (Cg25) as a critical member of this network, with additional evidence demonstrating sustained Cg25 overactivity in TRD patients.

Studies in the surgical treatment of Parkinson's disease have shown that chronic stimulation of specific brain regions can alter activity with the neural networks involved in motor activity and lead to significant improvements in the symptoms of the disease. Based on this line of reasoning, our group in Toronto piloted Deep Brain Stimulation (DBS) of the white matter immediately adjacent to Cg25 as a means for therapeutically altering function of putative depression networks in patients with TRD. Based on the encouraging first findings demonstrating sustained clinical benefit of chronic DBS of this region, this new study will further test the safety, efficacy, and mechanisms of action of this approach as a treatment strategy in a new group of TRD patients.

Twenty TRD patients will be enrolled and implanted with bilateral electrodes in the subgenual cingulate white matter using MRI guidance. Following randomized and blinded determination of the sites of stimulation within each hemisphere producing the most robust acute mood effects, a placebo-controlled trial of chronic stimulation of the identified optimal targets will be initiated for 1 month. The blinded control period will be followed by open chronic stimulation at the selected contacts for a period of 6 months. Pre-operative medications will be continued without changes to evaluate specific effects of chronic DBS. The 6 month chronic stimulation period will be followed by a blinded discontinuation period to further characterize persistent DBS effects and their time course. Stimulation will be resumed at pre-discontinuation parameters if patients show a depressive relapse without stimulation. Patients will be followed closely throughout the study to monitor the effects of acute and chronic DBS on their mood, cognition, and overall well-being using standardized neurological and psychiatric rating scales. DBS electrodes will remain implanted and chronic stimulation continued indefinitely unless there are complications requiring discontinuation and/or explantation. Potential mechanisms mediating DBS effects will also be assessed using a variety of measurements including sleep, neuroendocrine, neuropsychological, EEG, and neuroimaging studies (fMRI, blood flow PET, diffusion tensor tractography), Such studies will also be used to further define potential responder-nonresponder differences that might impact future patient selection.

Investigator Biographies

Helen Mayberg, M.D.

Dr. Mayberg is Professor of Psychiatry and Neurology at the Emory University School of Medicine. Her studies over the past 20 years have systematically examined neural mechanisms mediating depression pathogenesis in both psychiatric and neurological patient subgroups, as well as antidepressant response to various treatments including pharmacotherapy, cognitive behavioral therapy, and placebo with the goal of identifying neurobiological markers predicting treatment response and optimized treatment selection. Her long-term interest in neural network models of mood regulation in health and disease led to the recent development of a new intervention for treatment resistant patients using deep brain stimulation, a study initiated at the University of Toronto and now continuing at Emory.

Dr. Mayberg is a Board Certified Neurologist, trained at Columbia’s Neurological Institute in New York, with fellowship training in nuclear medicine at Johns Hopkins. She received a B.A. in Psychobiology from UCLA and an M.D. from the University of Southern California. She has held previous academic appointments in Neurology, Psychiatry, and Radiology at John Hopkins School of Medicine, the University of Texas Health Sciences Center in San Antonio, and the University of Toronto, where she was also the first Sandra Rotman Chair in Neuropsychiatry.