Background: Treatment-resistant depression presents a serious challenge to both patients and clinicians. The anterior and midlateral prefrontal cortices play complementary roles in integrating emotional and cognitive experiences and in modulating subcortical regions. Both regions offer a distinct opportunity for targeted antidepressant treatments. We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment-resistant depression. Methods: We enrolled five adults with an average of 5.8 failed antidepressant treatments in their current depressive episode. All subjects underwent comprehensive clinical assessments, detailed neuropsychological testing, and presurgical magnetic resonance imaging. Four cortical stimulation paddle leads were stereotactically placed bilaterally over the anterior frontal poles and midlateral prefrontal cortex. We also acquired a postsurgical computed tomography scan and repeatedly assessed clinical outcomes over time of EpCS as an adjunctive treatment to constant medications. Results: All patients tolerated the therapy. At 7-month follow-up, the average improvement from preimplant baseline on the Hamilton Rating Scale for Depression and the Inventory of Depressive Symptoms-Self-Report were 54.9% (± 37.7) and 60.1% (± 34.1), respectively. Three implanted subjects reached remission. One patient's left hemisphere leads were explanted 12 weeks postsurgery because of a scalp infection. Conclusions: Bilateral EpCS over anterior and midlateral frontal cortex is a promising new technology for treatment-resistant depression. Future double-blind studies are warranted.
Bibliographical noteFunding Information:
Dr. Nahas reports having received consulting fees from Neuronetics, Inc. and Cyberonics, Inc.; research funding from the National Institute of Mental Health (NIMH), National Alliance of Research for Schizophrenia and Depression, Hope for Depression Research, Neuronetics, Inc., Cyberonics, Inc., Medtronic, Inc. (in the form of device donations for this study), Brainsway, and Integra. Dr. George reports research funding from GlaxoSmithKline, Jazz Pharmaceuticals, NIMH, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, and the Ralph H. Johnson VA Medical Center. Dr. George reported consulting for Bristol-Meyers-Squibb, DarPharma, GlaxoSmithKline, Jazz Pharmaceuticals, Parke Davis, Aspect Medical, Brainsway, Brainsonix (unpaid), Cephos (unpaid), Cyberonics, Inc., Dantex, Medi-Physics/Amersham, Neuronetics, Inc. (unpaid), and Neuropace. Dr. George also reported that the Medical University of South Carolina has filed eight patents or invention disclosures under his name regarding brain imaging and brain stimulation. Dr. Borckardt receives research funding from the National Institute for Neurological Disorders and Stroke and the National Institute of Nursing Research at the National Institutes of Health, Cyberonics, Inc., and the Neurosciences Institute at MUSC. Dr. Borckardt is a consultant for Neuropace. Dr. Reeves, Dr. Tackacs, Mr. Anderson, and Ms. Arana reported no biomedical financial interests or potential conflicts of interest.
This study was funded primarily by a National Alliance of Research for Depression and Schizophrenia (NARSAD) Independent Investigator Award to ZN. It was also made possible with general funds from the Mood Disorders Program, the Brain Stimulation Laboratory, the General Clinical Research Center, the Center for Advanced Imaging Research at the Medical University of South Carolina. Medtronic, Inc. (Minneapolis, MN) donated the devices but was otherwise not involved in the study, particularly data acquisition, analysis, or drafting the article. We thank Mark Rise (Medtronic, Inc.) for technical assistance in stimulation setups and Sarah Coker (now a postgraduate year I psychiatry resident at Medical University of South Carolina [MUSC]) for assistance in the accuracy of lead placement analysis.
- Anterior poles
- brain stimulation
- epidural cortical stimulation
- frontal lobes
- medial prefrontal cortex