Non-Inferiority of Accelerated vs. Repetitive Transcranial Magnetic Stimulation in Major Depressive Disorder: A Systematic Review

Abstract

Introduction: Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique used to treat Major Depressive Disorder (MDD), particularly in patients with Treatment Resistant Depression (TRD). More recently, Accelerated Transcranial Magnetic Stimulation (aTMS) has shown comparable efficacy while offering a faster treatment option. This review assesses whether aTMS is non-inferior to rTMS. Methods: This systematic review compared aTMS and rTMS protocols for MDD treatment. Studies were identified through PubMed, Cochrane Library, and Web of Science (September 2024). Non-MDD populations and non-aTMS techniques were excluded, such as studies that did not qualify as clinical trials, cohort or randomized controlled trial. Inclusion criteria required direct protocol comparisons and a minimum sample of 10 participants. Bias assessment followed the Cochrane Collaboration's robvis tool. Results: Four studies were included, encompassing a total sample of 219 patients. Results showed symptom improvement across all groups, with accelerated protocols demonstrating faster response in some cases. However, long-term efficacy varied, and no study provided conclusive superiority of one protocol over the other. Discussion: This study reveals the variability in aTMS protocols and the inconsistency in the depression rating scales selected across studies, noting that the lack of standardised assessment methods limits meta-analytical potential. Short follow-up durations contrast with antidepressant studies, restricting long-term efficacy evaluation. Additionally, improvements in sham methodologies have increased placebo responses, further influencing treatment outcome interpretation. Conclusion: This systematic review highlights the efficacy, tolerability, and cost-effectiveness of aTMS, suggesting its non-inferiority to rTMS and underscoring the need for further research to define the optimal accelerated protocol.