THE ASSOCIATION BETWEEN DEPRESSION DURATION, THE SEVERITY OF PSYCHOSOCIAL STRESS, AND ANTIDEPRESSANT EFFICACY OF PREFRONTAL STIMULATION IN PATIENTS WITH TREATMENT-RESISTANT DEPRESSION

Abstract Background While psychosocial stress and episode duration do influence the treatment of depression, their effects on the antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS) are not yet well evaluated. Methods Data from a randomized, double-blind, sham-controlled prolonged intermittent theta-burst stimulation (piTBS) trial on the treatment of depression were utilized in this exploratory study. For a two-week intervention, 105 patients with treatment-resistant depression were randomly assigned to receive piTBS, 10Hz-rTMS, or sham monotherapy. The sham group was used the sham coil that could mimic the auditory and somatosensory effects of active coil stimulation without actual stimulation of the brain. 17-item Hamilton Depression Rating scale (HDRS-17) were obtained at baseline, week-1 and week-2. The baseline Holmes– Rahe Life-Stress Inventory was utilized to categorize patients into conditions of low and high severity of psychosocial stress. The cut-off value that separates between acute and chronic current episode duration was established at one year. The primary outcome was the %HDRS-17 changes after treatment. Results In contrast to the sham intervention, piTBS exhibited a noteworthy decrease in HDRS-17 for both low- stress acute and chronic depression (-47% vs. 12%, p<0.001; -32% vs. −8%, p<0.05, respectively). However, for high-stress acute and chronic depression, there was no statistically significant difference of the efficacy between piTBS and sham group (-42% vs. −22%; -33% vs.−22%, respectively).In addition, although chronic depression exhibited a lower rate of remission compared to acute depression among patients who received piTBS, both of their HDRS-17 score consistently declined over the course of two weeks. Placebo effect was positively correlated to stress severity in sham stimulation, but did not contribute significantly to the antidepressant efficacy in active stimulation. Conclusion This is the first study to evaluate the importance of depression chronicity and psychosocial stress severity, and the antidepressant effects of rTMS. By utilizing these two readily accessible clinical predictors, rTMS treatment can be more tailored individually. In addition, our findings suggested that early consideration about providing prefrontal stimulation in depressed patients who do not respond to antidepressants.