Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression.

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.

Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a novel, noninvasive method of stimulating selected regions of the brain that has both research applications and potential clinical utility, particularly for depression. To conduct high-quality clinical studies of rTMS, it is necessary to have a convincing placebo (or sham) treatment. Prefrontal rTMS causes cutaneous discomfort and muscle twitching; therefore, an optimal control condition, ie, sham condition, would mimic the cutaneous sensation and muscular discomfort of rTMS without stimulating the brain. Ideally, the quality and intensity of the sham condition would feel identical to the quality and intensity of the rTMS condition, except that the sham would have no effect on cortical activity. We designed and built a focal electrical stimulation system as a sham rTMS condition. Although this electrical sham system is superior to methods used in previous studies, little is known about how the new electrical sham system compares with active rTMS in terms of the level of discomfort and type of sensation it produces. METHODS: We hypothesized that the electrical sham system may not mirror the experimental condition sufficiently. We studied this hypothesis under single-blind conditions in 15 healthy adults by administering either the real or sham rTMS at high and low intensities while subjects, who were unaware of condition, rated subjective qualities of the stimulation (such as tingling, pinching, and piercing), the scalp location of the perception, and the painfulness of the stimuli. RESULTS: At low-intensity stimulation, the two techniques (active and sham) differ with respect to the subjective quality of the sensation. The differences between real and sham rTMS were less dramatic at higher intensities. The best sham condition that most closely mimics real prefrontal rTMS requires individual titration of the intensity of electrical stimulation across a broad range. Performing this titration without unblinding patients is likely possible, but technically challenging. We propose a new approach to do this. CONCLUSION: We conclude that it is possible to create a truly indistinguishable sham condition (with appropriate acoustic masking as well), but more work is needed beyond these initial attempts.