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

BACKGROUND

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.

METHODS

In a retrospective analysis of clinical data, we examined efficacy of five rTMS stimulation sessions per day for five days ("5 × 5") (N = 40) of either piTBS or individualized, electroencephalogram-based "resonant frequency" (RF) stimulation, and used mixed-effects linear models to compare these accelerated protocols to a standard once-daily rTMS protocol where patients received one rTMS session per day, 5 days a week, for 6 weeks (N = 135).

RESULTS

Both protocols ameliorated MDD symptoms and there were no statistically significant differences in depression symptom changes (p = 0.07) between the accelerated 5 × 5 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) at treatment completion (treatment day 5 for the 5 × 5 patients and treatment day 30 for the conventional patients). There was no significant difference in improvement between the piTBS and RF 5 × 5 protocols (p = 0.9). A PHQ-9 median split of 5 × 5 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).

CONCLUSIONS

These results suggest 5 × 5 accelerated rTMS treatment may be as effective as once daily rTMS treatment for many patients, and should be explored in future randomized clinical trials. It is critical to perform prolonged follow-up assessments in such trials because the efficacy of accelerated treatment may not be accurately assessed until weeks after treatment completion.