Authors' objectives: We identified and summarised evidence addressing the following review question: What is the clinical and cost effectiveness of repetitive transcranial magnetic stimulation (rTMS) in people with major depressive disorder that has not responded to antidepressants, when compared with standard care?

Authors' results and conclusions: We identified a health technology assessment by Ontario Health (2021) that reported clinical-effectiveness evidence on the use of rTMS for depression and bipolar disorder. We updated the meta-analysis from Ontario Health and re-analysed pooled outcomes comparing rTMS with sham for major depression. Evidence that included bipolar disorder was excluded. In total, we included 29 primary studies that assessed outcomes on standard rTMS for major depression compared with sham. Of these, 20 studies evaluated high-frequency left dorsolateral prefrontal cortex TMS, eight evaluated low-frequency right dorsolateral prefrontal cortex rTMS and six evaluated bilateral rTMS. We also included three systematic reviews comparing rTMS and electroconvulsive therapy (ECT), identified from the Ontario Health (2021) report. Overall, we found high-frequency rTMS had reduced depression scores, with better response and remission rates compared with sham. These improvements were found both at the end of the acute treatment phase, and the follow-up phase. Conversely, low-frequency rTMS showed no difference in score, response rate or remission rates compared to sham treatment at either end of treatment or at follow-up. Bilateral rTMS only showed better reduction in depression scores and better response and relapse rates compared with sham in the follow-up phase. Many of the analyses, specifically those comparing high or low-frequency rTMS with sham, showed high statistical heterogeneity. This may be due to variation across the studies in terms of rTMS parameters, treatment phase length, follow-up length and patient groups. Some outcomes showed considerable heterogeneity (I2 > 75%); we have still included the pooled results in this review, but these results should be interpreted with caution. It should be noted that not all studies comparing rTMS with sham included post-treatment follow-up, and in those studies that did the follow-up periods were short. This makes it difficult to ascertain impact of rTMS on long-term remission, or rates of relapse. Furthermore, all studies involved an acute treatment period, after which no further maintenance treatment was given; therefore, the effectiveness of long-term, persistent rTMS treatment is uncertain. Evidence comparing rTMS with ECT was summarised in three systematic reviews; all evidence was assessing high-frequency left DLPFC rTMS. ECT showed a better reduction in overall depression score than rTMS, but there was no difference in response and remission rates. The economic literature suggests that rTMS may be a cost effective intervention, however, the evidence has not been developed for a UK NHS setting. There is pathway uncertainty with conflicting evidence as to what the optimal rTMS treatment sequence is. The de-novo modelling undertaken within this analysis concluded that rTMS was not cost effective when compared to ECT or pharmacotherapy. Sensitivity analyses suggest that the findings for rTMS in comparison to pharmacotherapy are broadly robust but that there is considerable uncertainty in the analysis comparing rTMS and ECT. In addition, there are a range of structural and pathway-based uncertainties which could not be fully captured within the sensitivity analyses. Therefore, the results and conclusions of the analysis remain uncertain for both comparisons.

Authors' recommendations: The use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of treatment-resistant major depression is partially supported by the evidence. The use of rTMS is well tolerated, leads to a medium-term (up to three months) reduction in depression score, and improves response and remission rates compared with sham treatment. De novo economic modelling is subject to considerable uncertainty. Further research is therefore recommended to better determine the case for cost effectiveness, to establish the long-term efficacy of rTMS including potential maintenance therapy, and to determine the appropriate placement of rTMS in the NHS Wales treatment pathway.

Authors' methods: The Evidence Appraisal Report is based on a literature search (strategy available on request) for published clinical and economic evidence on the health technology of interest. It is not a full systematic review but aims to identify the best available evidence on the health technology of interest. Researchers critically evaluate and synthesise this evidence. We include the following clinical evidence in order of priority: systematic reviews; randomised trials; non-randomised trials. We only include evidence for “lower priority” evidence where outcomes are not reported by a “higher priority” source. We also search for economic evaluations or original research that can form the basis of an assessment of costs/cost comparison. We carry out various levels of economic evaluation, according to the evidence that is available to inform this. In the initial screening of evidence for this report, we identified a recent health technology assessment from Ontario Health evaluating rTMS in treatment-resistant depression, including major depression, bipolar depression and mixed depression populations. The HTA included de novo meta-analyses of relevant studies comparing different rTMS modalities and sham rTMS, a review of systematic reviews comparing rTMS with ECT, and cost-effectiveness modelling. We adapted the Ontario Health report for the purposes of this evidence review, adapting only the evidence relevant to our selection criteria, i.e. evidence on major depression (or unipolar depression) with rTMS modalities of interest (high-frequency, low-frequency, and bilateral) and recalculated pooled outcome data for the meta-analyses in RevMan using a random effects model. We also looked for any randomised controlled trials that were published after the literature searches that informed the Ontario Health report to include in the analyses.

Authors' identified further research: HTW's Appraisal Panel recommended that further research be undertaken to establish the long-term efficacy of rTMS including: potential maintenance therapy; to determine the appropriate placement of rTMS in the NHS Wales treatment pathway; and to establish the likely economic impact of rTMS in managing patients with severe and treatment-resistant depression.

Project Status: Completed

Year Published: 2021

URL for published report: https://healthtechnology.wales/reports-guidance/transcranial-magnetic-stimulation/

English language abstract: An English language summary is available

Publication Type: Rapid Review

Country: Wales, United Kingdom

Organisation Name: Health Technology Wales

Contact Address: c/o Digital Health Care Wales, 21 Cowbridge Road East Cardiff CF11 9AD

Contact Name: Susan Myles, PhD

Contact Email: healthtechnology@wales.nhs.uk

Copyright: Health Technology Wales