• Kristoffer Johansson, Mats Adler, Ullvi Båve, Carl-Johan Ekman, and Johan Lundberg.
• Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet.
• Medicine (Baltimore). 2021 Apr 9; 100 (14): e25273e25273.

BackgroundThe optimal dose (number of pulses per session) of repetitive transcranial magnetic stimulation (rTMS), using the H-coil, in major depressive disorder (MDD) has not previously been reported.ObjectiveTo explore the relationship between rTMS dose and antidepressant effect, and collect data for the design of a definitive trial.MethodsThis was a double-blind, three-arm parallel-group, randomized [1:1:1], pilot trial conducted in Stockholm, Sweden (September 2014 to September 2016). The primary outcome was change in depression severity measured with the Montgomery Åsberg Depression Rating Scale (MADRS) after 4 weeks. Participants (n = 29) with MDD were randomized to 1000, 2000, or 4000 pulses of rTMS for 20 sessions during 4 weeks.ResultsAt 4 weeks, the 3 treatment groups reduced the mean MADRS (95% CI) by 11.6 (4.0-19.2), 9.1 (5.0-13.3), and 11.3 (4.1-18.5) points respectively. Eleven participants met criteria for response and 10 for remission. No serious adverse events occurred. Ratings of subjective memory improved in all groups. Exploring the effect of dose and time, 4000 pulses had the largest reduction in MADRS during the first 2 weeks. A comparison of change in MADRS between 2000 and 4000 pulses after 2 weeks will require a sample size of 66 patients at power .80 and alpha .05.ConclusionsIt is feasible to conduct a definitive trial investigating whether a higher number of magnetic pulses per treatment session gives a more rapid antidepressive response.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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