Background: A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated.
Objective: To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study.
Methods: Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest.
Results: During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥ 40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study.
Conclusion: Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.