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