Psychological Medicine

Review Article

Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials

M. T. Berlima1a2 c1, F. van den Eyndea1, S. Tovar-Perdomoa1 and Z. J. Daskalakisa3

a1 Neuromodulation Research Clinic, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada

a2 Depressive Disorders Program, Douglas Mental Health University Institute and McGill University, Montréal, Québec, Canada

a3 Brain Stimulation Treatment and Research Program, Centre for Addiction and Mental Health and University of Toronto, Ontario, Canada


Background Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs).

Method We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT).

Results Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant.

Conclusions HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.

(Received November 22 2012)

(Revised February 06 2013)

(Accepted February 07 2013)

(Online publication March 18 2013)

Key words

  • Acceptability;
  • efficacy;
  • major depression;
  • meta-analysis;
  • repetitive transcranial magnetic stimulation


c1 Address for correspondence: M. T. Berlim M.D., M.Sc., Douglas Mental Health University Institute, 6875 LaSalle Blvd, FBC-3 Pavilion, Montréal, Québec, Canada, H4H 1R3. (Email: