Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression

Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
Clinical Practice and Epidemiology in Mental Health 10/2011; 7(1):167-77. DOI: 10.2174/1745017901107010167
Source: PubMed


Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation.
A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation.
First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks).
rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response.

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Available from: Bernardo Dell’Osso, Nov 11, 2015
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    • "The primary studies used in the current meta-analysis were selected from the past 13 meta-analyses published between 2001–2010 (Dell'Osso et al. 2011). The details of the systematic literature search strategy used in each of these 13 meta-analyses are summarised in the Additional file 1: Table S1. "
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    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.
    Full-text · Article · Oct 2014
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    • "Methods A systematic review was conducted in alignment with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [24]. The review included studies published in English after the development of TMS in 1985 until February 2013 [17]. The search strategy examined the databases of Ovid PsycINFO, PubMed, Ovid Medline and Web of Science for studies that utilized TMS as a treatment with adolescents 12e18 years of age experiencing depressive symptomology. "
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    ABSTRACT: Background Depressive disorders are among the most commonly experienced mental health concerns and a leading cause of mortality in adolescence. Current treatment guidelines recommend the use of antidepressant medication, cognitive behavioral therapy or both treatments. Unfortunately 40–60% of adolescents fail to respond to these treatments, therefore a new effective alternative treatment modality would be of particular benefit. rTMS is effective in addressing treatment resistant depression in adults and investigation into its effectiveness with adolescent populations has begun. Objective To examine the existing literature regarding the efficacy and safety of rTMS treatment with adolescents experiencing depressive symptoms, especially research conducted since the last published review. Methods A systematic review was conducted in accordance with PRISMA guidelines. The databases of OVID PsycINFO, PubMed, Ovid Medline and Web of Science were searched for research utilizing rTMS treatment with adolescents experiencing depressive symptomology. Results The review identified seven studies that examined rTMS as a treatment for depressive symptomology in adolescence. Findings indicate rTMS is likely to be an effective treatment for young people with preliminary longitudinal results suggesting maintenance of effects 3 years post-treatment. Reported side effects have included headaches, scalp discomfort and single incidences of hypomania and seizure. All side effects were transitory and did not recur. Conclusion Preliminary results suggest rTMS is an effective and well tolerated antidepressant treatment for adolescents with treatment resistant depressive symptomology. Further research allowing for comparison across studies is necessary to establish the efficacy of rTMS in adolescent depression.
    Full-text · Article · Feb 2014 · Brain Stimulation
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    • "rTMS is a noninvasive technology that uses a pulsed electromagnetic field to modulate neuronal activity in the cortex of the brain [2], and there is growing evidence that it has antidepressant actions. According to most clinical studies and meta-analyses, highfrequency rTMS is more effective than a sham control in the treatment of MDD in the acute stage and during partial remission [3,4]. Some studies have even reported that the efficacy of rTMS and the longitudinal outcomes of rTMS-treated patients are at least as good as those obtained with ECT [5-7]. "
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    ABSTRACT: Depression is a chronic illness that generally requires lifelong therapy. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique with few side effects that has been reported to be useful in the treatment of depression. However, no studies to date have evaluated in a randomized controlled trial (RCT) the efficacy of rTMS for maintenance treatment of depression.Methods/design: In this article, we report the design and protocol of a randomized, single-blind, placebo-controlled, parallel-group, multicenter study in China to evaluate the efficacy of rTMS in the prevention of relapse of depressive symptoms. In total, 540 patients, aged 18 to 60 years, diagnosed with depression and experiencing an acute exacerbation of depressive symptoms, will be enrolled. The study will consist of four phases: a screening/tolerability phase of up to 7 days; an open-label, flexible-dose lead-in phase of 8 weeks; an open-label, fixed-dose stabilization phase of 6 weeks; and a single-blind relapse prevention phase of 12 months. During the open-label phase, all patients will be treated with venlafaxine. Remitters with Hamilton Rating Scale for Depression (HAM-D17) score <=7 will be eligible to enter the single-blind phase and will be randomly assigned to one of three groups: group 1 on active rTMS and venlafaxine; group 2 on sham rTMS and venlafaxine; and group 3 on venlafaxine alone. Efficacy will be evaluated during the study using relapse assessment (time between subject randomization to treatment and the first occurrence of relapse). Secondary outcome measures will include: symptom changes, measured by the HAM-D17; illness severity changes, measured by the Clinical Global Impression of Severity for Depression (CGI-S-DEP); and changes in subject functioning, assessed with the Personal and Social Performance (PSP)scale. Safety will be assessed throughout the study by monitoring of adverse events, clinical laboratory tests, electrocardiography (ECG), and measurements of vital signs (temperature, pulse, and blood pressure) and weight. Suicidality will be assessed by the Columbia Suicide Severity Rating Scale (C-SSRS). The result of this trial will assess the efficacy of rTMS in the prevention of relapse of symptoms of depression by determining whether rTMS in combination with an antidepressant is more efficacious than the antidepressant alone for maintenance of the clinical response.Trial registration: NCT01516931.
    Full-text · Article · Oct 2013 · Trials
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