Elsevier

Journal of Affective Disorders

Volume 187, 15 November 2015, Pages 73-83
Journal of Affective Disorders

Review
Deep transcranial magnetic stimulation (DTMS) in the treatment of major depression: An exploratory systematic review and meta-analysis

https://doi.org/10.1016/j.jad.2015.08.033Get rights and content

Highlights

  • High-frequency deep transcranial magnetic stimulation (DTMS) has antidepressant properties in mostly treatment-resistant patients with unipolar depression.

  • Acute, 20 daily sessions of DTMS reduced depression severity based on data from nine open-label studies with 150 patients.

  • The acute response, remission, and dropout rates were 60%, 29%, and 18% respectively.

  • All antidepressant effects tended to be lower in studies with DTMS as a monotherapy compared to studies with DTMS as an add-on to pharmacotherapy.

Abstract

Background

Deep transcranial magnetic stimulation (DTMS) is a relatively new, non-invasive method of stimulating larger and, presumably, deeper brain regions. The current study investigated if DTMS delivered with H-coils has acute antidepressant effects in major depression using a systematic literature review and a quantitative meta-analysis.

Methods

Seventeen studies on ‘DTMS or H-coil’ and ‘depression’ were identified on Medline, PsycInfo, and Google Scholar (until November 2014). Data from nine open-label studies were meta-analysed using a random-effects model with inverse-variance weights. The outcome measures were the standardised paired mean difference (Cohen's d) in depression scores on Hamilton Depression Rating Scale (HDRS), response, remission, and dropout rates after acute DTMS treatment compared to baseline.

Results

There was a large antidepressant effect after 20 acute, high-frequency DTMS sessions compared to baseline according to HDRS change scores (overall mean weighted d=2.04, 95% confidence interval: 1.53–2.55; nine studies; 150 patients). Overall weighted response, remission, and dropout rates were 60%, 29%, and 18% respectively. HDRS change scores and response rates tended to be higher in four studies with 68 patients on concurrent antidepressants compared to two studies with 26 patients who received DTMS as a monotherapy.

Limitations

These results are based on data from a low number of open-label studies.

Conclusion

High-frequency DTMS appears to have acute antidepressant effects after 20 sessions in mostly unipolar and treatment-resistant patients. Concurrent treatment with antidepressants might enhance the efficacy of DTMS.

Introduction

According to the largest randomised-controlled trials (RCTs), high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective and well tolerated treatment for major depression, particularly in patients with resistant conditions (George et al., 2010, O’Reardon et al., 2007). The largest meta-analyses to date have shown that the antidepressant effects of acute HF-rTMS treatment were moderate to large in magnitude (Berlim et al., 2013b, Berlim et al., 2014b, Kedzior et al., 2014, Kedzior and Reitz, 2014). Particularly, HF-rTMS was associated with a clinically-relevant remission rate of approximately 30% (George et al., 2013).

A novel alternative to the conventional figure-of-eight or circular rTMS coils is the so-called H-coil system (Roth et al., 2002) whose derived therapeutic application has been called the deep transcranial magnetic stimulation (DTMS) (Levkovitz et al., 2009). The H-coil was developed to enable a focused, non-invasive stimulation of deeper brain regions while reducing the activation of cortical areas (Roth et al., 2002). It can be speculated that if the H-coils are indeed able to stimulate deeper reward-mediating neural pathways then they might produce antidepressant effects of greater magnitudes compared to the conventional rTMS coils which directly activate mostly superficial cortical regions (Roth et al., 2002). However, no head-to-head study has yet compared the efficacy of HF-rTMS and DTMS.

Although the antidepressant properties of the H-coils have been assessed in patients with major depression since 2009, no quantitative meta-analysis regarding its effectiveness and acceptability has been published to date. The results of a recent large multisite RCT involving patients with treatment-resistant, unipolar depression suggest that active DTMS monotherapy was significantly more effective than sham DTMS in reducing depression scores and improving response and remission rates (Levkovitz et al., 2015). However, it remains unexplored how the results from this RCT (Levkovitz et al., 2015) compare to those of open-label DTMS studies in major depression which are usually more representative of the ‘real world’ clinical populations. Therefore, the main aim of the current study was to systematically review the existing literature on the clinical utility of DTMS in major depression and quantitatively synthesise the findings using a meta-analysis.

Section snippets

Systematic literature search and study selection

The systematic literature search was performed in the EBSCO PsycInfo and Medline databases from any date until November 18, 2014. The search terms included DTMS (or H-coil) and depression (Table 1). The electronic search identified k=14 studies published in peer-reviewed academic journals. Three additional studies (in press at the time of search) were identified using Google Scholar.

The study selection procedure and exclusion criteria are summarised on the PRISMA flowchart (Moher et al., 2009),

Study characteristics

The nine open-label studies included 162 patients (at baseline) and were conducted in Israel (k=6), Italy (k=2), and Canada (k=1; Table 2, Table 5). The RCT (Levkovitz et al., 2015) included 181 patients (at baseline) and was a multicentre study conducted at 20 medical centres in the USA, Israel, Germany, and Canada (Table 2, Table 5).

Discussion

Based on the results of the current exploratory meta-analysis of nine open-label studies and the outcome of the only RCT published to date (Levkovitz et al., 2015), it appears that high-frequency DTMS is efficacious and acceptable as an acute treatment for major depression. The large magnitude of the overall effect size based on the pre-post differences in HDRS scores in the current analysis was likely inflated by the open-label nature of the included studies (i.e. the possible placebo and

Conclusions

The current study suggests that the high-frequency DTMS is efficacious and acceptable in the treatment of particularly unipolar and resistant depression. Future studies should investigate if concurrent treatment with antidepressants could further enhance the efficacy of DTMS and if the effects of DTMS would persist beyond the acute stimulation phase without maintenance treatment. Furthermore, the effectiveness of DTMS needs to be tested in larger samples with bipolar depression. It is also of

Acknowledgements

We thank Professor Zangen, Dr. Rapinesi, Dr. Kotzalidis, and Dr. Roth for commenting on this work and providing additional data.

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