Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades

Unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression: a meta-analysis of randomized controlled trials over 2 decades

J Psychiatry Neurosci 2019;44(3):151-163 | PDF | Appendix

Shayan Sehatzadeh, MD, MSc; Zafiris J. Daskalakis, MD, PhD; Belinda Yap, MPH, PhD; Hong-Anh Tu, PhD; Stefan Palimaka, MBiotech; James M. Bowen, MSc; Daria J. O’Reilly, PhD, MSc


Background: Approximately 35% of people with depression do not respond to 2 courses of antidepressant medications of adequate dosage, and treatment-resistant depression (TRD) is still a major clinical concern with a great impact on patients, their families, society and the health system. The present meta-analysis evaluates antidepressant efficacy of unilateral and bilateral repetitive transcranial
magnetic stimulation (rTMS) in patients with unipolar TRD.

Methods: We searched for randomized controlled trials that compared rTMS with sham treatment and were published by Apr. 3, 2017. The primary outcome was improvement in depression scores measured using the Hamilton Rating Scale for Depression. The secondary outcomes were remission and response rates. Two independent review authors screened the studies and extracted the data.

Results: Twenty-three studies met the inclusion criteria. Meta-analysis of the depression scores showed a weighted mean difference (WMD) of 3.36 (95% confidence interval [CI] 1.85–4.88) between unilateral rTMS and sham treatment. Stratified data showed that the effect was relatively higher when rTMS was used as an add-on to antidepressant medications (WMD 3.64, 95% CI 1.52–5.76) than when it was used as a stand-alone treatment (WMD 2.47, 95% CI 0.90–4.05). The WMD between bilateral rTMS and sham was 2.67 (95% CI 0.83–4.51), and all studies that contributed to this outcome used rTMS while participants were taking antidepressant medications. The pooled remission and response rates for unilateral rTMS versus sham treatment were 16.0% and 25.1% for rTMS and 5.7% and 11.0% for sham treatment, respectively. The pooled remission and response rates for bilateral rTMS versus sham treatment were 16.6% and 25.4% for rTMS and 2.0% and 6.8% for sham treatment, respectively.

Conclusion: This study suggests that rTMS has moderate antidepressant effects and appears to be promising in the short-term treatment of patients with unipolar TRD.

Submitted Apr. 12, 2018; Revised July 29, 2018; Accepted Sept. 19, 2018; Published online Feb. 5, 2019

Acknowledgements: The authors gratefully acknowledge and thank Caroline Higgins for conducting the literature search and creating the EndNote library.

Affiliations: From Health Quality Ontario, Toronto, Ont., Canada (Sehatzadeh, Tu, Palimaka); the Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ont., Canada (Daskalakis); the Programs for Assessment of Technology in Health (PATH), The Research Institute of St. Joe’s Hamilton, Hamilton, Ont., Canada (Yap, Bowen, O’Reilly); and the Department of Health Research Methods, Evidence and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Ont., Canada (Bowen, O’Reilly).

Competing interests: S. Palimaka was employed by Janssen Canada from September 2015 to October 2016 and has been employed by Amaris, Inc. since February 2017. No other competing interests declared.

Contributors: S. Sehatzadeh, Z.J. Daskalakis, H.-A. Tu, S. Palimaka, J.M. Bowen and D.J. O’Reilly designed the study. S. Sehatzadeh, B. Yap and H.-A. Tu acquired the data, which S. Sehatzadeh and J.M. Bowen analyzed. S. Sehatzadeh wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Disclaimer: The conclusions expressed in this publication do not necessarily represent the opinions of Health Quality Ontario. No endorsement is intended or should be inferred.

DOI: 10.1503/jpn.180056

Correspondence to: S. Sehatzadeh, Health Quality Ontario, 130 Bloor St. West, 10th floor, Toronto ON M5S 2B2; shayan.sehatzadeh@hqontario.ca