title: Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study.
abstract: 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.
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan ctil2@vghtpe.gov.tw tpsu@vghtpe.gov.tw.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Li
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Mu-Hong
authors.initials: MH
authors.lastname: Chen
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Juan
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Hsiang-Hsuan
authors.initials: HH
authors.lastname: Huang
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Chen
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Jen-Chuen
authors.initials: JC
authors.lastname: Hsieh
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Tu
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Shin-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Ying-Chiao
authors.initials: YC
authors.lastname: Lee
authors.affiliation: 1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan ctil2@vghtpe.gov.tw tpsu@vghtpe.gov.tw.
authors.forename: Tung-Ping
authors.initials: TP
authors.lastname: Su
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D003863:Depression / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D013826:Theta Rhythm / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents
keywords: antidepressant efficacy; brain stimulation; sham response; theta-burst stimulation; treatment-refractory depression