Study timeline -Treatment consisted of an arTMS course of 6 sessions/day (50 min inter-sessions intervals) over 5 days (on weekdays totalling 30 sessions. After a 1-week gap, arTMS was followed by a tapering course of once-daily stimulation (minimum of 20, maximum of 25 se days per week, to decrease the odds of relapse. Baseline visits were conducted the week prior to arTMS initiation and consisted of a clinical asse a trained research staff, navigation cap fitting and motor threshold calibration. Patients were clinically reassessed at 3 subsequent timepoints: po visits were conducted during the one-week gap following arTMS; post-taper visits were conducted within 7 days of tapering termination; 1-month visits were conducted 1-month (± 7 days) after the last tapering session. arTMS = accelerated repetitive transcranial magnetic stimulation, ATHF Antidepressant Treatment History Form, MINI = Mini International Neuropsychiatric Interview, BDI-II = Beck Depression Inventory-II, HRSD-17 = Hamilton Rating Scale for Depression ys), thus sessions), 3-5 ssessment by post-acute th follow-up F = Average = 17-item . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Study timeline -Treatment consisted of an arTMS course of 6 sessions/day (50 min inter-sessions intervals) over 5 days (on weekdays totalling 30 sessions. After a 1-week gap, arTMS was followed by a tapering course of once-daily stimulation (minimum of 20, maximum of 25 se days per week, to decrease the odds of relapse. Baseline visits were conducted the week prior to arTMS initiation and consisted of a clinical asse a trained research staff, navigation cap fitting and motor threshold calibration. Patients were clinically reassessed at 3 subsequent timepoints: po visits were conducted during the one-week gap following arTMS; post-taper visits were conducted within 7 days of tapering termination; 1-month visits were conducted 1-month (± 7 days) after the last tapering session. arTMS = accelerated repetitive transcranial magnetic stimulation, ATHF Antidepressant Treatment History Form, MINI = Mini International Neuropsychiatric Interview, BDI-II = Beck Depression Inventory-II, HRSD-17 = Hamilton Rating Scale for Depression ys), thus sessions), 3-5 ssessment by post-acute th follow-up F = Average = 17-item . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is effective in major depressive disorder (MDD). However, technical complexity and operational costs might have been barriers for its wide use and implementation in some jurisdictions, thereby decreasing accessibility. OBJECTIVE Our main goal was to test the feasibility of a novel rTMS...

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... We would like to thank Terri Cairo, Julian Kwok, Meaghan Todd, Nuno Ferreira, Thomas Russell and Eileen Lam for their involvement and organizational support throughout this project. This manuscript has been released as a pre-print at medRxiv (Miron et al., 2020b). ...
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Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.
... However, arTMS has not been well studied for 1 Hz protocols ( Miron et al., 2020a( Miron et al., , 2020b. On conventional once-daily regimens, 1 Hz has shown superiority over sham, with some studies also suggesting similar efficacy to high-frequency (HF) ( Berlim et al., 2012 ;Brunoni et al., 2017 ;Lefaucheur et al., 2020 ;Milev et al., 2016 ;Miron et al., 2020a ). 1 Hz also offers several potential advantages over HF, including less seizure risks ( Sun et al., 2012 ;Vila-Rodriguez et al., 2015 ), better tolerability ( Kaur et al., 2019 ), and the potential for implementation on simpler, lower-cost equipment ( Miron et al., 2020b( Miron et al., , 2020a, thus possibly increasing scalability and accessibility. ...
... However, arTMS has not been well studied for 1 Hz protocols ( Miron et al., 2020a( Miron et al., , 2020b. On conventional once-daily regimens, 1 Hz has shown superiority over sham, with some studies also suggesting similar efficacy to high-frequency (HF) ( Berlim et al., 2012 ;Brunoni et al., 2017 ;Lefaucheur et al., 2020 ;Milev et al., 2016 ;Miron et al., 2020a ). 1 Hz also offers several potential advantages over HF, including less seizure risks ( Sun et al., 2012 ;Vila-Rodriguez et al., 2015 ), better tolerability ( Kaur et al., 2019 ), and the potential for implementation on simpler, lower-cost equipment ( Miron et al., 2020b( Miron et al., , 2020a, thus possibly increasing scalability and accessibility. ...
... To date, we are only aware of 2 trials having studied 1 Hz arTMS specifically: an initial one was completed in a small patient cohort ( N = 7) and used a limited number of sessions (18 over 10 days) ( Tor et al., 2016 ). More recently, our group published another 1 Hz arTMS trial, where 48 participants received 6 daily sessions of 1 Hz arTMS over 5 days (30 sessions total) ( Miron et al., 2020b ). In this study, which employed a ring-shaped rather than figure-8 coil over F4, we reported modest response and remission rates of 25.0% and 16.7% on the BDI-II 1 week after treatment. ...
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BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention in major depressive disorder (MDD) but requires daily travel to a treatment clinic over several weeks. Shorter rTMS courses retaining similar effectiveness would thus increase the practicality and scalability of the technique, and therefore its accessibility. OBJECTIVE We assessed the feasibility of a novel 5 day accelerated 1 Hz rTMS protocol. We hypothesized that this novel rTMS protocol would be safe and well-tolerated while shortening the overall treatment course. METHODS We conducted a prospective, single-arm, open-label feasibility study. Thirty (30) participants received a one-week (5 days) accelerated (8 sessions per day, 40 sessions total) course of 1 Hz rTMS (600 pulses per session, 50-minute intersession interval) over the right dorsolateral prefrontal cortex (R-DLPFC) using a figure-of-eight coil at 120% of the resting motor threshold (rMT). Primary outcomes were response and remission rates on the Beck Depression Inventory-II (BDI-II). RESULTS Response and remission rates 1 week after treatment were 33.3% and 13.3% respectively and increased to 43.3% and 30.0% at follow-up 4 weeks after treatment. No serious adverse events occurred. All participants reported manageable pain levels. CONCLUSION 1 Hz rTMS administered 8 times daily for 5 days is safe and well-tolerated. Validation in a randomized trial will be required. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04376697.