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

doi:10.1016/j.ajp.2023.103891

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

Asian J Psychiatr. 2024 Feb:92:103891. doi: 10.1016/j.ajp.2023.103891. Epub 2023 Dec 25.

Authors

Chia-Ling Yu¹, Yu-Chen Kao², Trevor Thompson³, Andre R Brunoni⁴, Chih-Wei Hsu⁵, Andre F Carvalho⁶, Che-Sheng Chu⁷, Ping-Tao Tseng⁸, Yu-Kang Tu⁹, Fu-Chi Yang¹⁰, Kuan-Pin Su¹¹, Shu-Li Cheng¹², Tien-Wei Hsu¹³, Chih-Sung Liang²

Affiliations

¹ Department of Pharmacy, Chang Gung Memorial Hospital Linkou, Taipei, Taiwan.
² Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Centre, Taipei, Taiwan; Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan.
³ Centre for Chronic Illness and Ageing, University of Greenwich, London, UK.
⁴ Service of Interdisciplinary Neuromodulation, National Institute of Biomarkers in Psychiatry, Laboratory of Neurosciences (LIM-27), Departamento de Instituto de Psiquiatria, Faculdade de Medicina da University of Sao Paulo, Sao Paulo, Brazil; Departamento de Ciências Médicas, Faculdade de Medicina da University of São Paulo, São Paulo, Brazil.
⁵ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Taiwan.
⁶ IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
⁷ Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁸ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁹ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹⁰ Department of Neurology, Tri-Service General Hospital, National Defense Medical Centre, Taipei, Taiwan.
¹¹ College of Medicine, China Medical University, Taichung, Taiwan; Mind-Body Interface Laboratory (MBI-Lab), China Medical University and Hospital, Taichung 404, Taiwan; An-Nan Hospital, China Medical University, Tainan 709, Taiwan.
¹² Department of Nursing, Mackay Medical College, Taipei, Taiwan. Electronic address: slcheng@mmc.edu.tw.
¹³ Department of Psychiatry, E-DA Dachang Hospital, I-Shou University, Kaohsiung, Taiwan; Department of Psychiatry, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan. Electronic address: s9801101@gmail.com.

PMID: 38183740
DOI: 10.1016/j.ajp.2023.103891

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.

Keywords: Dose-response meta-analysis; High-frequency repetitive transcranial magnetic stimulation; Stimulation frequency; Total pulses; Treatment-resistant depression.

Publication types

Systematic Review
Meta-Analysis
Review

MeSH terms

Antidepressive Agents / therapeutic use
Depression
Depressive Disorder, Major* / drug therapy
Humans
Prefrontal Cortex
Randomized Controlled Trials as Topic
Transcranial Magnetic Stimulation*
Treatment Outcome

Substances

Antidepressive Agents