Trajectories of improvement with repetitive transcranial magnetic stimulation for treatment-resistant major depression in the BRIGhTMIND trial

Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive brain stimulation treatment for major depressive disorder, but there is marked inter-individual variability in response. Using latent class growth analysis with session-by-session patient global impression ratings from the recently completed BRIGhTMIND trial, we identified five distinct classes of improvement trajectory during a 20-session treatment course. This included a substantial class of patients noticing delayed onset of improvement. Contrary to prior expectations, members of a class characterised by early and continued improvement showed greatest inter-session variability in stimulated location. By relating target locations and inter-session variability to a well-studied atlas, we estimated an average of 3.0 brain networks were stimulated across the treatment course in this group, compared to 1.1 in a group that reported symptom worsening (p < 0.001, d = 0.893). If confirmed, this would suggest that deliberate targeting of multiple brain networks could be beneficial to rTMS outcomes.