Review
A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy

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Background

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.

Method

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.

Results

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.

Limitations

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.

Conclusions

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.

Introduction

There is a considerable interest worldwide in the use of subconvulsive repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression. rTMS has excited the interest of clinicians and been highly acceptable to patients (Walter et al., 2001), because of its ability to stimulate focal areas of brain cortex non-invasively using magnetic fields. Unlike ECT, it does not involve a general anaesthetic or seizure. In some countries, e.g. Canada and Israel, rTMS is approved for the clinical treatment of depression. In Australia, the Royal Australian and New Zealand College of Psychiatrists Position Statement on TMS (2003) recognizes the need for further research into TMS but cautiously allows for its clinical use to treat depression in limited circumstances, with recommended caveats, including that the patient sign a consent form acknowledging that “the most efficacious manner of administering rTMS has not yet been established”.

The International Society for Transcranial Stimulation Consensus Statement on the use of rTMS is mainly concerned with advising on safety and procedural issues in whatever context rTMS is used (Belmaker et al., 2003). There has been a debate on the advisability of broadening the use of rTMS to clinics beyond research centres, with discussion of associated regulatory issues (e.g. Fitzgerald, 2003a, Sachdev, 2003). Apart from considerations of safety, adequate regulatory safeguards and the limitations of current therapeutic options in treatment resistant depression, a critical appraisal of the efficacy of rTMS as a treatment for depression is central to this debate. This article evaluates the efficacy outcomes reported so far in clinical trials of rTMS, and discusses the potential of future strategies to optimize the efficacy of rTMS.

Section snippets

Studies of the efficacy of rTMS in depression

Given the relatively large number of published rTMS treatment trials but relatively small sample sizes in each (see Table 1 for summary of sham-controlled trials), it is perhaps most constructive to begin by reviewing the seven published meta-analyses (including a Cochrane Review) (McNamara et al., 2001, Holtzheimer et al., 2001, Burt et al., 2002, Kozel and George, 2002, Martin et al., 2003, Aarre et al., 2003, Couturier, 2005).

The earliest meta-analysis (McNamara et al., 2001) only included

Strategies to optimize the efficacy of rTMS

As can be seen from Table 1, studies have varied greatly in the choice of rTMS parameters used (stimulus frequency (i.e. number of pulses per second), intensity, number of stimuli), with an even larger range of possible combinations of these. Almost no two studies have used identical rTMS parameters, except in deliberate attempts at replication, making comparisons of efficacy difficult. As yet, there is little empirical evidence to guide the choice of these parameters.

Conclusion

Most of the sham-controlled data for the efficacy of rTMS in treating depression comes from studies with a two-week sham-controlled period. The outcomes suggest clear statistical proof of superiority over placebo effects but not large clinical effects. However, the few studies which have reported results of longer periods of stimulation suggest that a longer course of rTMS is necessary for optimal therapeutic outcomes. Thus evidence for the efficacy of rTMS should be derived from

Acknowledgements

Dr. Loo is a part-time Senior Research Fellow supported by a National Health and Medical Council Program Grant no. 2223208. The authors thank Kate Manollaras for assistance in manuscript preparation.

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