Invasive Neuromodulation Techniques for Treatment-Resistant Depression

Surgically implanted neurostimulation devices for the treatment of depression have been studied for the last three decades. While the surgical risk associated with these treatment approaches clearly limits their use to the most severely impacted depressed patients, they offer a unique opportunity to better understand the impact of relatively localized alteration of neural activity in patient groups. As a result, these approaches provide a strict test of the role of individual neural structures or networks in mechanistic models of depression. In this chapter, we review the proposed mechanisms of action and evidence for clinical efficacy of vagal nerve stimulation, deep brain stimulation, and epidural cortical stimulation in patients with depression. The evidence for efficacy remains limited for all three modalities, but the long-term follow-up studies of treated patients have highlighted the importance of interactions between neural regions in determining therapeutic response, and suggest that personalized approaches to stimulation are likely to be required.