Loo CK, Mitchell PB. A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. J Affect Disord 88: 255-267

School of Psychiatry, University of NSW, Psychiatrist, Black Dog Institute and South Eastern Sydney Illawarra Area Health Service, Australia.
Journal of Affective Disorders (Impact Factor: 3.38). 12/2005; 88(3):255-67. DOI: 10.1016/j.jad.2005.08.001
Source: PubMed


There is a growing interest in extending the use of repetitive transcranial magnetic stimulation (rTMS) beyond research centres to the widespread clinical treatment of depression. Thus it is timely to critically review the evidence for the efficacy of rTMS as an antidepressant treatment. Factors relevant to the efficacy of rTMS are discussed along with the implications of these for the further optimization of rTMS.
Clinical trials of the efficacy of rTMS in depressed subjects are summarized and reviewed, focusing mainly on sham-controlled studies and meta-analyses published to date.
There is a fairly consistent statistical evidence for the superiority of rTMS over a sham control, though the degree of clinical improvement is not large. However, this data is derived mainly from two-week comparisons of rTMS versus sham, and evidence suggests greater efficacy with longer treatment courses. Studies so far have also varied greatly in approaches to rTMS stimulation (with respect to stimulation site, stimulus parameters etc) with little empirical evidence to inform on the relative merits of these approaches.
Only studies published in English were reviewed. Many of the studies in the literature had small sample sizes and different methodologies, making comparisons between studies difficult.
Current published studies and meta-analyses have evaluated the efficacy of rTMS as given in treatment paradigms that are almost certainly suboptimal (e.g of two weeks' duration). While the data nevertheless supports positive outcomes for rTMS, there is much scope for the further refinement and development of rTMS as an antidepressant treatment. Ongoing research is critical for optimizing the efficacy of rTMS.


Available from: Philip Bowden Mitchell
    • "In the initial years of the service, sequential bilateral rTMS was used, based upon the literature at that time which indicated a combined benefit of both left and right stimulation (Fitzgerald et al., 2006). A comparison of bilateral with low-frequency stimulation over the right DLPFC was then undertaken, as unilateral treatment was less time consuming and, if efficacy was similar, could be adopted instead of the bilateral protocol (Loo and Mitchell, 2005). In bilateral treatment sessions, intermittent high-frequency rTMS (10 Hz) delivered in 5-second intervals with a 25-second intertrain interval (1500 pulses) was applied to the left DLPFC for 15 minutes, followed immediately by 15 minutes of unilateral low-frequency rTMS (1 Hz) applied to the right DLPFC continuously at a rate of one pulse per second for 15 minutes (900 pulses). "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. Method: This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Results: Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N=167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N=123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. Conclusion: This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore, repetitive transcranial magnetic stimulation can provide a useful treatment alternative as part of outpatient mental health services for people with depression. © 2015 The Royal Australian and New Zealand College of Psychiatrists 2015.
    No preview · Article · Nov 2015 · Australian and New Zealand Journal of Psychiatry
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    • "Numerous studies on the efficacy of rTMS revealed that rTMS is an effective treatment option in major depressive disorder. In most meta-analyses, rTMS is superior to sham control (Burt, Lisanby, and Sackeim, 2002; Holtzheimer, Russo, and Avery, 2001; Kozel and George, 2002; Lam, Chan, Wilkins- Ho, and Yatham, 2008; Loo and Mitchell, 2005; McNamara, Ray, Arthurs, and Boniface, 2001; Schutter, 2009). In one exception, however, Couturier (2005) reported in his metaanalysis in 2005 that there were no significant differences between rTMS and sham control (Couturier, 2005). "
    [Show description] [Hide description] DESCRIPTION: Transcranial magnetic stimulation (TMS) was introduced as a novel method of brain stimulation in 1985, and now it is widely used in research of cortical excitability, neuronal connectivity and plasticity, and also is applied to the treatment of various neurological and psychiatric conditions. This review is written with the purpose of introducing the brief conspectus and area of therapeutic application of TMS. The techniques, equipment and treatment modalities of TMS are continuously developing, and its area of therapeutic application is being extended. For determining the form of the optimal therapeutic application of TMS in various clinical conditions, more data from controlled studies should be obtained.
    Full-text · Research · Aug 2015
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    • "Moreover, extreme right frontal asymmetry has been associated with affective disorders such as depression (Thibodeau et al., 2006) and social anxiety disorder (SAD; Moscovitch et al., 2011). In addition, increasing left-sided activity or decreasing right-sided activity with repetitive transcranial magnetic stimulation (rTMS) resulted in improvements in depression (for review see Loo and Mitchell, 2005) and anxiety (for review see Pallanti and Bernardi, 2009) symptoms. EEG neurofeedback is another method used to modulate cortical activity. "
    [Show abstract] [Hide abstract] ABSTRACT: Frontal asymmetry in alpha oscillations is assumed to be associated with psychopathology and individual differences in emotional responding. Brain-activity-based feedback is a promising tool for the modulation of cortical activity. Here, we validated a neurofeedback protocol designed to change relative frontal asymmetry based on individual alpha peak frequencies (IAF), including real-time average referencing and eye-correction. Participants (N=60) were randomly assigned to a right, left, or placebo neurofeedback group. Results show a difference in trainability between groups, with a linear change in frontal alpha asymmetry over time for the right neurofeedback group during rest. Moreover, the asymmetry changes in the right group were frequency and location specific, even though trainability did not persist at one week and one month follow-ups. On the behavioral level, subjective stress on the second test day was reduced in the left and placebo neurofeedback groups, but not in the right neurofeedback group. We found individual differences in trainability that were dependent on training group, with participants in the right neurofeedback group being more likely to change their frontal asymmetry in the desired direction. Individual differences in trainability were also reflected in the ability to change frontal asymmetry during the feedback. © The Author (2015). Published by Oxford University Press. For Permissions, please email:
    Full-text · Article · Jul 2015 · Social Cognitive and Affective Neuroscience
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