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Depression is one of the most prevalent mental illnesses worldwide and a leading cause of disability, especially in the setting of treatment resistance. In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative strategy for treatment-resistant depression and its clinical efficacy has been investigated intensively across the world. However, the underlying neurobiological mechanisms of the antidepressant effect of rTMS are still not fully understood. This review aims to systematically synthesize the literature on the neurobiological mechanisms of treatment response to rTMS in patients with depression. Medline (1996–2014), Embase (1980–2014) and PsycINFO (1806–2014) were searched under set terms. Three authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Of 1647 articles identified, 66 studies met both inclusion and exclusion criteria. rTMS affects various biological factors that can be measured by current biological techniques. Although a number of studies have explored the neurobiological mechanisms of rTMS, a large variety of rTMS protocols and parameters limits the ability to synthesize these findings into a coherent understanding. However, a convergence of findings suggest that rTMS exerts its therapeutic effects by altering levels of various neurochemicals, electrophysiology as well as blood flow and activity in the brain in a frequency-dependent manner. More research is needed to delineate the neurobiological mechanisms of the antidepressant effect of rTMS. The incorporation of biological assessments into future rTMS clinical trials will help in this regard.
Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs).
We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT).
Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant.
HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.
Bilateral repetitive magnetic stimulation (rTMS) is a promising novel therapeutic intervention for major depression (MD). However, clinical trials to date have reported conflicting evidence concerning its overall efficacy, which might have resulted from low statistical power. Thus, meta-analytical approaches could be useful in examining this issue by allowing the integration of findings from multiple studies and thus producing more accurate estimates of the treatment effect.
We searched the literature for randomized, double-blind and sham-controlled trials (RCTs) on bilateral rTMS for treating MD from 1995 to July 2012 using EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations and Theses, and from October 2008 until May 2012 using Medline. The main outcome measures were response and remission rates. We used a random-effects model, odds ratios (ORs) and the number needed to treat.
Data were obtained from seven RCTs, totaling 279 subjects with MD. After an average of 12.9 (s.d. = 2.7) sessions, 24.7% (40/162) and 6.8% (8/117) of subjects receiving active bilateral rTMS and sham rTMS were classified as responders [OR 4.3, 95% confidence interval (CI) 1.95–9.52, p < 0.0001]. Also, 19% (23/121) and 2.6% (2/77) of subjects were remitters following active bilateral rTMS and sham rTMS, respectively (OR 6.0, 95% CI 1.65–21.8, p = 0.006). No difference between baseline mean depression scores for the bilateral and sham rTMS groups was found, and the former was comparable with the latter in terms of drop-out rates at study end. Furthermore, we did not find significant differences efficacy- and acceptability-wise between active bilateral and unilateral rTMS at study end. Finally, heterogeneity between the included RCTs was not significant, and the risk of publication bias was found to be low.
Bilateral rTMS is a promising treatment for MD as it provides clinically meaningful benefits that are comparable with those of standard antidepressants and unilateral rTMS. Furthermore, bilateral rTMS seems to be an acceptable treatment for depressed subjects.
Although several studies have reported that repetitive transcranial magnetic stimulation (rTMS) treatment has demonstrable efficacy in patients with depression, the parameters needed to optimize therapeutic efficacy remain unclear. To this end we determined the efficacy of low-frequency right rTMS to the dorsolateral prefrontal cortex (DLPFC) compared to two forms of bilateral rTMS to the DLPFC: (1) sequential low-frequency right-sided followed by high-frequency left-sided rTMS and (2) sequential low-frequency rTMS to both hemispheres.
A total of 219 patients with treatment-resistant depression (TRD) were randomized to a 4-week course of rTMS applied with one of the three treatment conditions. Outcomes were assessed with standard rating scales.
Overall, slightly more than 50% of the patients achieved clinical response criteria. There was no substantial difference in response between the unilateral and bilateral treatment groups. Successful response to rTMS was predicted by a greater degree of baseline depression severity.
There is no substantial difference in efficacy between unilateral right-sided rTMS and the two forms of bilateral rTMS assessed in the study. Furthermore, our results call into question the specificity between frequency and laterality and rTMS response.