Targeting repetitive transcranial magnetic stimulation in depression: do we really know what we are stimulating and how best to do it?

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for patients with depression who have not achieved optimal outcomes with one or more trials of antidepressant medication. It is an effective antidepressant treatment but there remains considerable scope for improving clinical outcomes. One method to potentially enhance the efficacy of rTMS is through the improvement of methods of stimulation localization. Objective: The purpose of this paper is to review the literature pertaining to rTMS localization methods and approaches relevant to the treatment of major depressive disorder (MDD) and provide specific opinions on the state of the art in regards to targeting of rTMS treatment in depression. Methods: A targeted review of the literature on rTMS targeting in depression. Results: There is emerging evidence that optimal rTMS treatment outcomes are likely to be achieved with stimulation at a relatively anterior stimulation site in the left dorsolateral prefrontal cortex (DLPFC). However, some lines of research suggest that there may be two effective stimulation sites: one quite posterior, and one more anterior, in the DLPFC. The ‘Beam F3’ method provides reasonable localization to the anterior stimulation site and the posterior stimulation site corresponds to that typically used in studies using the ‘5 cm method’. Neuro-navigational methods are generally most likely to consistently ensure placement of the TMS coil such that it results in stimulation of a selected cortical site. fMRI – connectivity based approaches to targeting specific circuits in the DLPFC are intellectually attractive but it may not be possible to demonstrate differential effectiveness of these over the methods most commonly been used in clinical practice. Conclusions: There is an emerging literature helping to improve our understanding of the optimal methods for targeting rTMS treatment for depression. However, we lack substantive prospective clinical trials demonstrating improved clinical outcomes with these techniques.