The association of total pulses with the efficacy of repetitive transcranial magnetic stimulation for treatment-resistant major depression: A dose-response meta-analysis

Chia Ling Yu, Yu Chen Kao, Trevor Thompson, Andre R. Brunoni, Chih Wei Hsu, Andre F. Carvalho, Che Sheng Chu, Ping Tao Tseng, Yu Kang Tu, Fu Chi Yang, Kuan Pin Su, Shu Li Cheng*, Tien Wei Hsu*, Chih Sung Liang

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Aim: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC). Materials and methods: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses. Results: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56–0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R2 =0.53) and age(R2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15–20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15–1.10) when combining all doses. Conclusions: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy.

Original languageEnglish
Article number103891
Pages (from-to)103891
JournalAsian Journal of Psychiatry
Volume92
DOIs
StatePublished - 02 2024

Bibliographical note

Copyright © 2024 Elsevier B.V. All rights reserved.

Keywords

  • Dose-response meta-analysis
  • High-frequency repetitive transcranial magnetic stimulation
  • Stimulation frequency
  • Total pulses
  • Treatment-resistant depression
  • Humans
  • Depressive Disorder, Major/drug therapy
  • Depression
  • Treatment Outcome
  • Prefrontal Cortex
  • Randomized Controlled Trials as Topic
  • Transcranial Magnetic Stimulation
  • Antidepressive Agents/therapeutic use

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