Potential new brain stimulation therapies in bipolar illness: Transcranial magnetic stimulation and vagus nerve stimulation

The advances in understanding the functional and structural anatomy of bipolar affective disorder (BPAD) outlined in the rest of this volume provide the background and rationale for attempting to manipulate these regions as potential antidepressant and anti-manic therapies. The idea of using circuit and device based approaches to regulating mood follows in the tradition of electroconvulsive therapy (ECT). In marked contrast to ECT, however, these new stimulation techniques represent an important new paradigm shift, with treatments that neither produce seizures nor require general anesthesia. The new techniques are safer, with fewer side effects, and are more focal than ECT in their entry into the brain. Transcranial magnetic stimulation (TMS) produces direct cortical brain stimulation by creating a powerful transient magnetic field. Five published randomized controlled trials suggest it has clinically significant acute antidepressant effects. One controlled study suggests that it may have antimanic effects as well. Vagus nerve stimulation (VNS) involves direct electrical stimulation of the vagus nerve in the neck, with propagation of the signal to the brainstem. One controlled and one open study in epilepsy patients with depression found antidepressant effects of VNS. An open study of VNS in treatment resistant unipolar and bipolar depression found acute antidepressant effects. These two device-based approaches to stimulating the brain offer promise as potential acute and even long-term treatments. Imaging studies suggest that TMS likely causes changes in mood regulating regions by stimulating limbic regions from the cortex down, while VNS influences this same circuit from the brainstem up. These two approaches are not yet approved by the Food and Drug Administration (FDA) for use in the US, although pivotal trials geared for eventual FDA approval are underway. Finally, the research determining whether and how these devices work to influence mood also promises to help unravel the pathophysiology of BPAD.