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

Abstract

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.

Keywords: Deep transcranial magnetic stimulation (DTMS); Figure-of-eight coil (F8-coil); H1-coil; Major depressive disorder (MDD); Meta-analysis; Repetitive transcranial magnetic stimulation (rTMS).

Fig. 1

Study selection procedure (PRISMA flowchart). a. DTMS studies with H1-coil. b. rTMS studies with F8-coil. Note. Abbreviations: DTMS, deep transcranial magnetic stimulation; F8, figure-of-eight coil (rTMS); H1, H1-coil (DTMS); HDRS, Hamilton Depression Rating Scale; k, number of studies; RCT, double-blind randomised-controlled trial with an inactive sham group; rTMS, repetitive transcranial magnetic stimulation.

Fig. 2

Antidepressant outcomes in all studies with either coil (F8-coil and H1-coil). a. Primary outcome (depression severity): standardised HDRS change score at baseline (pre) – session 10 (post). b. Secondary outcome (response rates at session 10 vs. baseline). c. Secondary outcome (remission rates at session 10 vs. baseline). Note. Figures a-c are forest plots of random-effects meta-analyses of the antidepressant outcomes in all studies with either coil (F8-coil and H1-coil). Each forest plot shows the following information: the antidepressant outcomes expressed as effect sizes in each study (Hedges’ g or event rates depicted as squares), the estimated 95% CI of each effect size (reported in the Lower limit and the Upper limit columns and shown as horizontal lines), the study weights (depicted as squares with different sizes- the larger the square, the higher the study weight), the study sample sizes (reported in the Total columns), and the pooled mean weighted effect sizes with 95% CI of all studies (depicted as diamonds- the length of the diamond corresponds to the 95% CI of the pooled effect). Abbreviations: CI, 95% confidence interval; DTMS, deep transcranial magnetic stimulation; F8, figure-of-eight coil (rTMS); H1, H1-coil (DTMS); HDRS, Hamilton depression rating scale; Hedges’ g (effect size), standardised paired difference in means corrected for the sample size; rTMS, repetitive transcranial magnetic stimulation; Total, sample size per study

Fig. 3

Relationships between primary outcome (depression severity), mean age, and stimulation intensity. a. Depression severity vs. mean age in all studies with either coil (F8-coil and H1-coil). b. Depression severity vs. stimulation intensity (%MT) in all studies with either coil. c. Depression severity vs. stimulation intensity (%MT) in studies with F8-coil. Note. Figures a-c are scatterplots of random-effects meta-regressions. All plots show the relationships between depression severity expressed as weighted effect sizes in each study (Hedges’ g depicted as circles- the larger the circle, the higher the study weight) on the Y-axes and predictors on the X-axes (mean age of all patients per study or stimulation intensity per study). Outlier studies were excluded from the analyses. Abbreviations: DTMS, deep transcranial magnetic stimulation; F8, figure-of-eight coil (rTMS); H1, H1-coil (DTMS); Hedges’ g (effect size), standardised paired difference in means corrected for the sample size; %MT, percent of the resting motor threshold; rTMS, repetitive transcranial magnetic stimulation

Fig. 4

Antidepressant outcomes in DTMS studies with H1-coil vs. rTMS studies with F8-coil. a. Primary outcome (depression severity): standardised HDRS change score at baseline (pre) – session 10 (post). b. Secondary outcome (response rates at session 10 vs. baseline). c. Secondary outcome (remission rates at session 10 vs. baseline). Note. Figures a-c are forest plots of mixed-effects meta-analyses comparing the antidepressant outcomes in studies with F8-coil vs. H1-coil. In contrast to Fig. 2, each forest plot shows two diamonds corresponding to the pooled mean weighted effects of studies with F8-coil (the upper diamonds) vs. studies with H1-coil (the lower diamonds). Abbreviations: CI, 95% confidence interval; DTMS, deep transcranial magnetic stimulation; F8, figure-of-eight coil (rTMS); H1, H1-coil (DTMS); HDRS, Hamilton depression rating scale; Hedges’ g (effect size), standardised paired difference in means corrected for the sample size; rTMS, repetitive transcranial magnetic stimulation; Total, sample size per study