Two commonly used transcranial magnetic stimulation strategies for major depressive disorder produced different short-term outcomes in a randomized clinical trial, with intermittent theta-burst stimulation associated with greater improvements in depressive symptoms and emotion regulation.
In the study, patients receiving intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex experienced larger reductions in depression severity over a two-week treatment period than those treated with a sequential bilateral protocol that combined iTBS to the left dorsolateral prefrontal cortex followed by low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex.
The trial enrolled 114 adults diagnosed with major depressive disorder, of whom 106 completed the intervention. Patients were randomly assigned to one of the two active neuromodulation approaches and underwent treatment sessions over two consecutive weeks. Depression severity was assessed using the Hamilton Depression Rating Scale (HAMD), with additional measures examining anxiety, anhedonia, and emotion-regulation strategies.
Both groups entered the study with comparable demographic and clinical characteristics. Following treatment, symptom reduction was greater among patients treated with iTBS. Mean HAMD scores decreased by 14.88 points in the iTBS group compared with 7.88 points among those receiving sequential bilateral rTMS.
Differences between the approaches were also observed in measures of emotional regulation. Patients receiving iTBS showed greater increases in cognitive reappraisal—an emotion-regulation strategy that involves reinterpreting negative experiences—as well as larger reductions in expressive suppression. Anxiety symptoms also declined to a greater extent in the iTBS group, although some secondary outcomes did not remain significant after adjustment for multiple comparisons.
Further analyses suggested a relationship between improvements in cognitive reappraisal and reductions in depressive symptoms among patients treated with iTBS, a pattern not observed in the sequential bilateral rTMS group.
Both neuromodulation strategies were generally well tolerated. Mild adverse events, including headache and dizziness, were reported in a small number of patients, and no serious adverse events occurred during the study period.
The researchers note that both stimulation approaches are designed to modulate prefrontal brain circuits involved in emotional control. However, intermittent theta-burst stimulation delivers patterned bursts over a shorter time period, which may more efficiently engage left prefrontal networks linked to cognitive regulation of emotion.
The researchers caution that the absence of a sham control group and the short follow-up period limit interpretation of the findings. Further studies will be needed to assess longer-term outcomes and clarify the mechanisms underlying the observed differences.
The authors declared having no competing interests.
Source: Frontiers in Neuroscience
