Antidepressant outcomes of high-frequency repetitive transcranial magnetic stimulation (rTMS) with F8-coil and deep transcranial magnetic stimulation (DTMS) with H1-coil in major depression: a systematic review and meta-analysis

Background The current study aims to systematically assess and compare the antidepressant outcomes of repetitive transcranial magnetic stimulation (rTMS) with the figure-of-eight (F8)-coil and deep transcranial magnetic stimulation (DTMS) with the H1-coil in studies matched on stimulation frequency in unipolar major depressive disorder (MDD). Methods Electronic search of Medline and PsycInfo identified 19 studies with stimulation frequency of 18–20 Hz using F8-coil (k = 8 randomised sham-controlled trials, RCTs, k = 3 open-label; n = 168 patients) or H1-coil (k = 1 RCT, k = 7 open-label; n = 200). Depression severity (the primary outcome) and response/remission rates (the secondary outcomes) were assessed at session 10. Results Effects pooled with random-effects meta-analysis showed a large reduction in depression severity, 29% response, and 15% remission rates after 10 sessions of active stimulation with either coil relative to baseline. Reduction in depression severity was greater in studies with younger patients using either coil. The comparison between coils showed a larger reduction in depression severity in H1-coil vs. F8-coil studies (independent of the study design or the concurrent pharmacotherapy) and a trend towards higher remission rates in F8-coil vs. H1-coils studies. These effects are based on a low volume of studies, are not controlled for placebo, and may not be clinically-relevant. The stimulation protocols differed systematically because stimulation was more focal but less intense (80–110% of the resting motor threshold, MT) in the F8-coil studies and less focal but more intense (120% MT) in the H1-coil studies. Two seizures occurred in the H1-coil studies relative to none in the F8-coil studies. Conclusion When matched on frequency, the higher-intensity and less focal stimulation with the H1-coil reduces depression more than the lower-intensity and more focal stimulation with the F8-coil. Head-to-head trials should compare the antidepressant outcomes of F8-coil and H1-coil to identify the most optimal stimulation protocols for acute and longer-lasting efficacy. Electronic supplementary material The online version of this article (10.1186/s12888-019-2106-7) contains supplementary material, which is available to authorized users.


Table of Contents
Note. Figures A-B are forest plots of the random-effects meta-analyses of the primary antidepressant outcome (depression severity at baseline (pre) -session 10 (post)) in all studies with either coil (F8-coil and H1-coil). Figure S1A shows the results of an outlier analysis. The effect size (Hedges' g) in one study (Chen et al., 2013) was significantly (p<.01) higher than all other effects in rTMS studies with F8-coil. The removal of this study did not change the interpretation of the pooled mean weighted effect that was 1.20 with and 1.15 without the study by Chen et al., 2013, respectively ( Figure S1B).

Figure S3. Depression severity: publication bias analysis
Note. The funnel plot shows a distribution of all effect sizes (the unfilled circles) around the pooled mean weighted effect of all studies (the unfilled diamond). Four studies theoretically missing from the analysis (the filled circles) are required to make the plot symmetric. The interpretation of the analysis including the missing studies (the filled diamond) is the same as without these studies (the unfilled diamond). If the missing studies indicate that publication bias occurred, such bias has no effect on the interpretation of the results of this analysis.  Note. Figures A-B

Figure S5. Response rates: publication bias analysis
Note. The funnel plot shows a distribution of all effect sizes (the unfilled circles) around the pooled mean weighted effect of all studies (the unfilled diamond). Two studies theoretically missing from the analysis (the filled circles) are required to make the plot symmetric. The interpretation of the analysis including the missing studies (the filled diamond) is the same as without these studies (the unfilled diamond). If the missing studies indicate that publication bias occurred, such bias has no effect on the interpretation of the results of this analysis.  Note. Figures A-B

Figure S7. Remission rates: meta-regression analysis
Note. The figure is a scatterplot of random-effects meta-regression. The plot shows the relationships between remission rates expressed as weighted effect size in each study (logit event rate depicted as circles-the larger the circle, the higher the study weight) on the Y-axis and predictor on the X-axis (stimulation intensity, %MT, per study) using data from studies with either coil (F8-coil and H1-coil).

Figure S8. Remission rates: publication bias analysis
Note. The funnel plot shows a distribution of all effect sizes (the unfilled circles) around the pooled mean weighted effect of all studies (the unfilled diamond). Six studies theoretically missing from the analysis (the filled circles) are required to make the plot symmetric. The interpretation of the analysis including the missing studies (the filled diamond) is the same as without these studies (the unfilled diamond). If the missing studies indicate that publication bias occurred, such bias has no effect on the interpretation of the results of this analysis.

B. Add-on studies
Note. Figures A-B

B. Add-on studies
Note. Figures A-B

B. Add-on studies
Note. Figures A-B    • U 1 indicates that the random sequence generation and/or the allocation concealment were not described in the double-blind randomised controlled-trials with inactive sham groups (both risks are likely to be low) • U 2 indicates that studies reported outcomes for completers only meaning that the risk of attrition bias is unclear