Efficacy of 5x5 accelerated versus conventional repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression

Abstract Accelerated repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), with an FDA-cleared protocol utilizing 10 sessions of prolonged intermittent Theta Burst Stimulation (piTBS) per day for five days. However, it remains unclear how many sessions and pulses are necessary to achieve benefit. We examined efficacy of five stimulation sessions per day for five days (“5x5”) of either piTBS or individualized, electroencephalogram-based “resonant frequency” (RF) stimulation. We compared MDD symptom improvement (PHQ-9) between two groups: 1) accelerated patients (N = 40) undergoing 5x5 treatment (patients received piTBS or RF rTMS) and 2) conventional patients (N = 135) receiving standard once daily rTMS. Both protocols ameliorated MDD symptoms and there were no statistically significant differences in depression symptom changes (p = .07) between the accelerated 5x5 protocol (mean PHQ-9: pre-rTMS = 17.68, post-rTMS = 10.98) and conventional once-daily treatment (mean PHQ-9: pre-rTMS = 17.83, post-rTMS = 8.97). There was no significant difference in improvement between the piTBS and RF 5x5 protocols (p = 0.9). A PHQ-9 median split of 5x5 patients revealed that the top half of patients showed robust depression improvement (69%) while the bottom half received no significant benefit (8%) by day 5. However, the bottom half showed significant improvement (36%) at two-to-four-week follow up (p = 0.001). These results suggest 5x5 accelerated rTMS treatment is as effective as once daily rTMS treatment and that the efficacy of accelerated treatment may not be accurately assessed until weeks after treatment completion.