The association between sample and treatment characteristics and the efficacy of repetitive transcranial magnetic stimulation in depression: A meta-analysis and meta-regression of sham-controlled trials

Background: Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neuromodulation that is increasingly used to treat major depressive disorder (MDD). However, treatment with rTMS could be optimized by identifying optimal treatment parameters or characteristics of patients that are most likely to benefit. This meta-analysis and meta-regression aims to identify sample and treatment characteristics that are associated with change in depressive symptom level, treatment response and remission. Methods: The databases PubMed, Embase, Web of Science and Cochrane library were searched for randomized controlled trials (RCTs) reporting on the therapeutic efficacy of high-frequent, low-frequent, or bilateral rTMS for MDD compared to sham. Study and sample characteristics as well as rTMS parameters and outcome variables were extracted. Effect sizes were calculated for change in depression score and risk ratios for response and remission. Results: Sixty-five RCTs with a total of 2982 subjects were included in this meta-analysis. Active rTMS resulted in a larger depressive symptom reduction than sham protocol (Hedges’ g = −0.791 95% CI −0.977; −0.605). Risk ratios for response and remission were 2.378 (95% CI 1.882; 3.005) and 2.450 (95% CI 1.779; 3.375), respectively. We found no significant association between sample and treatment parameters and rTMS efficacy. Conclusions: rTMS is an efficacious treatment for MDD. No associations between sample or treatment characteristics and efficacy were found, for which we caution that publication bias, heterogeneity and lack of consistency in the definition of remission might bias these latter null findings. Our results are clinically relevant and support the use of rTMS as a non-invasive and effective treatment option for depression.