Efficacy, efficiency and safety of high-frequency repetitive transcranial magnetic stimulation applied more than once a day in depression: A systematic review

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression but a standard course can be time-consuming. Of all rTMS protocols, high-frequency rTMS (HF rTMS) is the most studied and applied in clinical settings. Little is known about applying multiple sessions of HF rTMS per day, in so-called accelerated schedules. Methods: We systematically searched electronic records up to September 2019 for studies that applied HF rTMS in accelerated schedules to treat depression to review its efficacy, efficiency and safety. Treatment effect sizes of accelerated rTMS versus standard and sham rTMS were calculated from comparison studies and pooled to derive overall treatment effect. Results: Of 1,361 records screened, 12 met review criteria. Qualitative synthesis suggested accelerated HF rTMS was equally effective as once-daily scheduling in treating depression. It is equivocal if accelerated HF rTMS results in more rapid antidepressant response. Accelerated HF rTMS was well-tolerated. The small number of studies suitable for quantitative analysis led to pooled effect sizes that did not reach statistical significance. Limitations: There was an overall paucity of studies examining the accelerated application of HF rTMS and even fewer studies comparing accelerated HF rTMS with once-daily or sham rTMS. Conclusion: Our review found comparable antidepressant efficacy between accelerated and once-daily HF rTMS. Between group differences in therapeutic effect sizes were not clinically meaningful. More studies investigating accelerated rTMS protocols are needed to validate its utility and guide clinical decision making.