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Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study

Cheng-Ta Li, Mu-Hong Chen, Chi-Hung Juan, Hsiang-Hsuan Huang, Li-Fen Chen, Jen-Chuen Hsieh, Pei-Chi Tu, Ya-Mei Bai, Shin-Jen Tsai, Ying-Chiao Lee, Tung-Ping Su
DOI: http://dx.doi.org/10.1093/brain/awu109 2088-2098 First published online: 10 May 2014

Summary

Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.

  • treatment-refractory depression
  • theta-burst stimulation
  • antidepressant efficacy
  • brain stimulation
  • sham response
  • Abbreviations
    CGI-S
    Clinical Global Impression Scale
    HDRS
    Hamilton Depression Rating Scale
    TBS
    theta-burst stimulation
    TMS
    transcranial magnetic stimulation
    TRD
    treatment-refractory depression
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