So far no convincing answer has emerged to the question of whether transcranial magnetic stimulation (TMS) can make a clinically useful contribution to the treatment of depression. Here we examine whether multiple sensitivity analyses can highlight parameters that predict a favorable treatment response.
Medline, Embase, and the Cochrane database for controlled trials were searched for relevant randomized controlled trials using the expression (transcranial magnetic stimulation or TMS) and depression.
Thirty-three studies were identified and included in the random-effects meta-analysis, and between 17 and 31 studies were included in the secondary analyses comparing outcome of studies with different parameters.
Study data were extracted with a standardized data sheet. A meta-analysis based on Cohen d effect size measure was done for all studies and various subsets. Regression analysis of effect sizes with study parameters was done in 24 studies.
Active TMS treatment was more effective than sham, but variability was too great to take any single study design as paradigmatic. No significant predictors of study effect size were found. Mean effect sizes were reduced, although still significant, in studies with stimulation intensity below 90% of motor threshold and new medication starting within 7 days before to 7 days after start of TMS.
The absence of significant outcome predictors in the presence of significant variability of outcome measures can be interpreted in 2 ways: either study sizes and numbers and designs are insufficient to afford the power necessary to detect such predictors or TMS has a nonspecific effect on depression that is not influenced by study parameters. Large-scale comparative trials are necessary to decide between these interpretations.
"Furthermore, rTMS was effective as a monotherapy, in studies with patients on concurrent antidepressants (Burt et al. 2002; Herrmann and Ebmeier 2006; Slotema et al. 2010), and in studies with treatment-resistant patients (Herrmann and Ebmeier 2006; Lam et al. 2008; Schutter 2009). The authors of some meta-analyses suggested that the antidepressant effect of rTMS could be enhanced in less severely resistant patients (Gross et al. 2007; Holtzheimer et al. 2001). "
[Show abstract][Hide abstract] ABSTRACT: According to a narrative review of 13 meta-analyses (published up to 2010), repetitive transcranial magnetic stimulation (rTMS) has a moderate, short-term antidepressant effect in the treatment of major depression. The aim of the current study was to reanalyse the data from these 13 meta-analyses with a uniform meta-analytical procedure and to investigate predictors of such an antidepressant response.
A total of 40 double-blind, randomised, sham-controlled trials with parallel designs, utilising rTMS of the dorsolateral prefrontal cortex in the treatment of major depression, was included in the current meta-analysis. The studies were conducted in 15 countries on 1583 patients and published between 1997-2008. Depression severity was measured using the Hamilton Depression Rating Scale, Beck Depression Inventory, or Montgomery Åsberg Depression Rating Scale at baseline and after the last rTMS. A random-effects model with the inverse-variance weights was used to compute the overall mean weighted effect size, Cohen's d.
There was a significant and moderate reduction in depression scores from baseline to final, favouring rTMS over sham (overall d = -.54, 95% CI: -.68, -.41, N = 40 studies). Predictors of such a response were investigated in the largest group of studies (N = 32) with high-frequency (>1 Hz) left (HFL) rTMS. The antidepressant effect of HFL rTMS was present univariately in studies with patients receiving antidepressants (at stable doses or started concurrently with rTMS), with treatment-resistance, and with unipolar (or bipolar) depression without psychotic features. Univariate meta-regressions showed that depression scores were significantly lower after HFL rTMS in studies with higher proportion of female patients. There was little evidence for publication bias in the current analysis.
Daily rTMS (with any parameters) has a moderate, short-term antidepressant effect in studies published up to 2008. The clinical efficacy of HFL rTMS may be better in female patients not controlling for any other study parameters.
"Although there is persuasive evidence for the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) (Hermann and Ebmeier 2006; Slotema et al. 2010), there is only limited knowledge about the underlying molecular mechanisms. Brain-derived neurotrophic factor (BDNF) is suggested to be involved in the pathogenesis of depression (Jacobs et al. 2000). "
[Show abstract][Hide abstract] ABSTRACT: Although repetitive transcranial magnetic stimulation (rTMS) is established in the treatment of depression, there is little knowledge about the underlying molecular mechanisms. In the last decade, the neurotrophic hypothesis of depression entailed a plethora of studies on the role of neurogenesis-associated factors in affective disorders and rTMS treatment. In the present study, we hypothesised a sham-controlled increase of peripheral brain-derived neurotrophic factor (BDNF) levels following serial rTMS stimulations in healthy individuals. We investigated the influence of a cycle of nine daily high-frequency (HF)-rTMS (25 Hz) stimulations over the left dorsolateral prefrontal cortex (DLPFC) on serum levels of BDNF in 44 young healthy male volunteers. BDNF serum concentrations were measured at baseline, on day 5 and on day 10. Overall, the statistical analyses showed that the active and sham group differed significantly regarding their responses of BDNF serum levels. Contrary to our expectations, there was a significant decrease of BDNF only during active treatment. Following the treatment period, significantly lower BDNF serum levels were quantified in the active group on day 10, when compared to the sham group. The participants' smoking status affected this effect. Our results suggest that serial HF-rTMS stimulations over the left DLPFC decrease serum BDNF levels in healthy male volunteers. This provides further evidence for an involvement of BDNF in clinical rTMS effects.
"In this context, novel neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), hold promise as putative non-pharmacological augmenting strategies for TRD. High frequency (HF) rTMS, in particular, has been shown in several randomized controlled trials (RCTs) (O'Reardon et al., 2007; George et al., 2010; Avery et al., 2006; Fitzgerald et al., 2003) and meta-analyses (Slotema et al., 2010; Herrmann and Ebmeier, 2006; Lam et al., 2008) to be effective for treating MDD. However, most previous trials have only used rTMS as monotherapy for MDD (i.e., concomitant use of antidepressants was not allowed). "
[Show abstract][Hide abstract] ABSTRACT: Randomized, controlled trials (RCTs) have found repetitive transcranial magnetic stimulation (rTMS) to be effective for major depression, but its usefulness as an augmenting strategy for severe treatment-resistant depression (TRD) has yet to be firmly established.
In a naturalistic trial, 15 chronically depressed, severely treatment-resistant patients were treated with daily high frequency (HF) rTMS over the left dorsolateral prefrontal cortex (DLPFC) for 4 weeks as an augmenting strategy. Depressive and anxious symptoms (both subjective and objective), as well as quality of life (QOL) domains were measured pre-post rTMS treatment.
Pre-post rTMS comparisons revealed significant reductions of both clinician-rated and selfreport depression and anxiety measures and increases in three (out of five) domains of subjective QOL (i.e., global, physical, and psychological).
Small sample size and non-controlled design.
Our results suggest that HF rTMS, when used as an augmenting strategy, positively affects depressive and anxious symptoms as well as QOL in patients with severe TRD. However, further studies with larger samples and controlled designs are needed to better clarify our preliminary findings.
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