Abstract
Late-life depression (LLD) is a growing worldwide problem due to demographic changes, with limited treatment options due to high rates of pharmacotherapy adverse effects, accessibility of psychotherapy, and tolerability of electroconvulsive therapy. Novel neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), may overcome these limitations. The objective of this study is to determine the efficacy, tolerability, and cognitive effects of high-dose deep rTMS in LLD. In this study we randomized older adults between 60 and 85 years old with major depressive disorder (MDD) to sham or active deep rTMS (H1 coil, 6012 pulses, 18 Hz, 120% of resting motor threshold) delivered over the dorsolateral and ventrolateral prefrontal cortex 5 days per week over 4 weeks. Our primary outcome was remission of depression in an intention-to-treat analysis. We also assessed change in cognitive functioning with rTMS treatment and tolerability based on adverse effects. Fifty-two participants were randomized to active (n = 25) or sham H1 coil (n = 27). Remission rate was significantly higher with active than sham rTMS (40.0% vs 14.8%) with a number needed to treat of 4.0 (95% CI: 2.1–56.5). There was no change on any measure of executive function and no serious adverse events. Adverse effect profiles were similar between active and sham rTMS, except for reports of pain being significantly more common in the active condition (16.0% vs 0%). High-dose deep rTMS appears to be safe, well tolerated, and efficacious in the treatment of LLD.
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Acknowledgements
We thank Marcos Sanches for his assistance with the statistical analysis. This study was supported by the Canadian Institute for Health Research University-Industry Sponsored Operating Grant in conjunction with Brainsway Ltd. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The authors attest that they had full access to all the data in the study and had final responsibility for the decision to submit the publication.
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TSK receives research support from the University of Toronto and the Clinician Scientist Program through the Department of Psychiatry at the University of Toronto. In the last 3 years, ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the Brain and Behaviour Research Foundation, the National Institutes of Mental Health and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. YN receives research support from Otsuka Pharmaceutical Co., Ltd, Shionogi & Co., Ltd, and Meiji Seika Pharma Co., Ltd. YN has also received research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, and Daiichi Sankyo Scholarship Donation Program. YN has received equipment in-kind support for an investigator-initiated study from Magventure Inc. YK has no disclosures. JD receives research support from CIHR, NIH, Brain Canada, Weston Brain Institute, and the Toronto General and Western Hospital Foundation, as well as in-kind (equipment) support from Magventure for an investigator-initiated study. TKR receives research support from the Weston Brain Institute, Canada Research Chair program, and the Canada Foundation for Innovation. YL has served as a consultant and has financial interests in Brainsway Ltd. AZ is a co-inventor of the TMS H-coils and serves as consultant for, and has financial interests in, Brainsway Ltd. He receives research support from the European Commission (Horizon 2020 program), NIH, the Israel Science Foundation, the Israel Ministry of Health and equipment support from Brainsway Ltd. MAB receives research support from the US National Institutes of Health (NIH). BHM currently receives research financial support from Brain Canada, the CAMH Foundation, the US Patient-Centered Outcomes Research Institute (PCORI), and the US National Institute of Health (NIH); and in-kind support from Capital Solution Design LLC (software used in a study founded by CAMH Foundation), Eli Lilly (medications for a NIH-funded clinical trial), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), HAPPYneuron (software used in a study founded by Brain Canada), and Pfizer (medications for a NIH-funded clinical trial). Within the past 5 years, he has also received research support from the Canadian Institutes of Health Research (CIHR), Bristol-Myers Squibb (medications for a NIH-funded clinical trial), Pfizer (medications for a NIH-funded clinical trial), and Eli Lilly (medications for a NIH-funded clinical trial). He directly owns stock of General Electric (less than $5000). DMB receives research support from the Canadian Institutes of Health Research (CIHR), Brain Canada, Weston Brain Institute, National Institutes of Health (NIH), Temerty Family through the Centre for Addiction and Mental Health (CAMH) Foundation, and the Campbell Family Research Institute. He received non-salary operating funds and in-kind equipment support from Brainsway Ltd for an investigator-initiated study. He is the site-principal investigator for three sponsor-initiated clinical trials from Brainsway Ltd. He received in-kind equipment support from Tonika/Magventure for an investigator-initiated study. He received medication supplies from Indivior for an investigator-initiated trial. He participated in one advisory board meeting for Janssen.
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Kaster, T.S., Daskalakis, Z.J., Noda, Y. et al. Efficacy, tolerability, and cognitive effects of deep transcranial magnetic stimulation for late-life depression: a prospective randomized controlled trial. Neuropsychopharmacol 43, 2231–2238 (2018). https://doi.org/10.1038/s41386-018-0121-x
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DOI: https://doi.org/10.1038/s41386-018-0121-x
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