Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression

Abstract

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.

Figures

Figure 1

Surgical planning and electrodes placement. Before surgery, the region of interests (Brodmann's areas [BA] 10 and 46 bilaterally) were identified and highlighted on each subject's magnetic resonance imaging (MRI) scan (A and B). In the operating room, the patient's head was coregistered with the MRI image using a stereotactic frameless system (BrainLab, Westchester, Illinois). A three-dimensional rendering displayed the head surface anatomy in native space with bilateral BA 10 and 46 in distinctive colors. An external wand helped identify landmarks of interest for accurate position of the leads. (A–C) The external wand pointing at the right midlateral region of interest (BA 46). The surgical team used intraoperative fluoroscopy (D) in conjunction with the stereotactic frameless system to optimize targeting accuracy.

Figure 2

Mean and standard error in 24-item Hamilton Rating Scale for Depression patients over time in five treatment-resistant depression-treated with adjunctive anterior pole and midlateral epidural prefrontal cortical electrical stimulation.