Combination rapid transcranial magnetic stimulation in treatment refractory depression

William M McDonald¹, Kirk Easley², Eve H Byrd¹, Paul Holtzheimer¹, Shannon Tuohy¹, John L Woodard³, Kimberly Beyer¹, Charles M Epstein⁴

¹Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA, USA; ²Department of Biostatistics, School of Public Health, Emory University, Atlanta, GA, USA; ³Department of Psychology and Department of Psychiatry and Behavioral Sciences, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA; ⁴Department of Neurology, Emory University Medical School, Atlanta, GA, USA

Abstract: High frequency (> 1 Hz) repetitive transcranial magnetic stimulation (rTMS) applied to the left prefrontal cortex and low frequency (≤ 1 Hz) rTMS applied to the right prefrontal cortex have shown antidepressant effects. However, the clinical significance of these effects has often been modest. It was hypothesized that a combination of these two techniques might act synergistically and result in more clinically relevant antidepressant effects. Sixty-two subjects with treatment-resistant major depression (an average of 8 failed medication trials) were randomized to receive combination right low frequency (1 Hz)/left high frequency (10 Hz) rTMS over the dorsolateral prefrontal cortex at 110% of the motor threshold vs sham rTMS. Subjects were treated for 2 weeks (10 weekday sessions) and received 1600 stimulations during each treatment session. Subjects receiving combination treatment were further randomized to receive different orders of treatment: right low frequency first (Slow Right) vs left high frequency first (Fast Left). There were no statistical differences in the active vs sham treatment arms in the primary outcome variable, the Hamilton Depression Rating Scale (HDRS). However compared with subjects in the Sham and Slow Right arms, there was a trend for subjects in the Fast Left arm to show improvement in the HDRS, the Beck Depression Inventory, and the Brief Psychotic Rating Scale with increased number of treatments. The Fast Left arm also showed significant improvement in both blinded clinician and self-ratings of global improvement. These differences were hypothesized to be due to the decreased number of failed medication trials for subjects in Fast Left arm. Neuropsychological performance was not significantly different between the sham and active rTMS arms. Future studies should increase the number of treatment sessions and focus on subjects with moderate treatment resistance.

Keywords: transcranial magnetic stimulation, treatment resistant depression