Comparison between accelerated and standard or sham rTMS in the treatment of depression: A systematic review

Major depressive disorder (MDD) represents a major global health challenge, with a significant proportion of patients being resistant to drug treatment (TRD). Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the treatment of MDD/TRD, with a single stimulation session per day for five days per week over several weeks (the "standard" protocol). The two main paradigms used are high-frequency rTMS and intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (DLPFC). Accelerated TMS (aTMS) protocols aim to make the treatment more effective, or at least more rapidly effective, by delivering more stimulations in a shorter time, which could also facilitate the implementation of the protocols for a larger number of patients. In this systematic literature review, articles comparing in the same study an aTMS protocol to a standard or sham rTMS protocol were retained for analysis. Thus, 23 articles were retained and the analysis focused on the efficacy of aTMS protocols used for the treatment of depression (MDD/TRD) as well as on the impact of various stimulation parameters, such as stimulation pattern, intersession interval, dosage, and methods of cortical targeting. Although some studies did not report significant differences between aTMS and standard or sham protocols, others suggested potential advantages of aTMS, such as twice-daily HF-rTMS of the left DLPFC or more intensive iTBS protocols with a long interval between two sessions and personalized cortical targeting. Our results highlight the influence of the number of sessions or pulses per session (dosage), the duration of the interval between sessions, and the precision of target localization (using image-guided neuronavigation) on therapeutic efficacy. However, limitations in sample size, few independent studies replicating the same methodology, and variability in the clinical profile of treated patients, given different definitions of treatment resistance or the presence of comorbidities, hamper definitive conclusions.