OBJECTIVES

Even though there are several clinical studies that have demonstrated the efficacy of unilateral high-frequency left sided (HFL) rTMS intervention in Major Depressive Disorder (MDD), the results of published meta-analysis are contradictory due to the heterogeneity of the included studies. Our aim is to provide an up-to-date synthesis of the evidence regarding the effectiveness of the rTMS technology.

METHODS

A systematic literature review (SLR) of English-language articles published in the last 10 years was performed from November 2020 on PubMed and Scopus databases according to PRISMA guideline principles. Empirical evidence on the efficacy of rTMS treatment in treatment-resistant depression (TRD) were extracted. To assess the effects of rTMS on response and remission rates we used random-effects model and inverse variance method. While the presence of heterogeneity was assessed using Cochran's Q-statistic and quantified using the I² statistics.

RESULTS

23 randomized double-blinded sham-controlled studies met the inclusion criteria for quantitative analysis for response (n= 1020 patients) and 12 studies for remission (n= 846 patients). The relative risk for response and remission were 2.47 (95% CI: 1.36-4.48, p=0.000) and 2.59 (95% CI: 1.52-4.41, p=0.000), respectively, in patients after two treatment failures using rTMS as add on treatment compared to standard pharmacotherapy. Cochrane’s Q analysis showed no significant heterogeneity in the combined effect sizes neither for remission studies (p_Q=0.013, I²=52.67) nor for response studies (p_Q=0.537, I²=0.00%). No publication bias was detected.

CONCLUSIONS

rTMS is rapidly gaining popularity as a treatment modality for TRD either as a monotherapy or as adjunct with pharmacotherapy, however because of the lack of standardized protocol, a substantial methodological heterogeneity exists. According to our results, unilateral HFL rTMS was significantly more effective than sham rTMS in both outcomes, which is consistent with previous meta-analyses, but the effect size was a bit smaller than what was reported previously.