Victor M. Tang, MSc, MD; Daniel M. Blumberger, MD, MSc; Julia Dimitrova, MSc; Alanah Throop, MPsy; Shawn M. McClintock, PhD; Daphne Voineskos, MD, PhD; Jonathan Downar, MD, PhD; Yuliya Knyahnytska, MD, PhD; Benoit H. Mulsant, MD, MS; Paul B. Fitzgerald, MBBS, MPM, PhD; Zafiris J. Daskalakis, MD, PhD
Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression.
Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests.
Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory.
Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters.
Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy.
Clinical trial registration: NCT01596608; clinicaltrials.gov
Submitted May 14, 2019; Revised Sept. 21, 2019; Accepted Oct. 18, 2019; Published online Jan. 10, 2020
Affiliations: From the Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Tang, Blumberger, Dimitrova, Throop, Voineskos, Knyahnytska, Mulsant, Daskalakis); the Neurocognitive Research Laboratory, Department of Psychiatry, University of Texas Southwestern Medical Center, and Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC (McClintock); the Centre for Mental Health and Krembil Research Institute, University Health Network, Department of Psychiatry, University of Toronto, Toronto, Ont., Canada (Downar); and the Epworth Centre for Innovation in Mental Health, Epworth Healthcare and Monash Alfred Psychiatry Research Centre, the Alfred and Monash University Central Clinical School, Melbourne, Australia (Fitzgerald).
Competing interests: D. Blumberger reports grants from Magventure during the conduct of the study; other funding from Brainsway; and grants from the National Institute of Mental Health, the Canadian Institutes of Health Research, Brain Canada and the Patient Centred Outcomes Research Institute, outside the submitted work. S. McClintock reports grants from the National Institutes of Health and personal fees from Pearson Assessment during the conduct of the study. D. Voineskos reports grants from the Ontario Mental Health Foundation and the Innovation Fund of the Alternate Funding Plan for the Academic Health Sciences Centres of Ontario, outside the submitted work. J. Downar reports personal fees from Restorative Brain Clinics, TMS Neuro Health and Neurostim TMS Clinics, outside the submitted work. B. Mulsant reports grants from Brain Canada, the Canadian Institutes of Health Research, the Centre for Addiction and Mental Health Foundation, the Patient-Centred Outcomes Research Institute and the United States National Institutes of Health; and non-financial support from Eli Lilly, Pfizer, Capital Solutions Design LLC, HAPPYneuron and General Electric, outside the submitted work. P. Fitzgerald is supported by a National Health and Medical Research Council Practitioner Fellowship (1078567) and has received equipment for research from MagVenture A/S, Medtronic Ltd, Neuronetics and Brainsway Ltd. and funding for research from Neuronetics; he is on scientific advisory boards for Bionomics Ltd and LivaNova and is a founder of TMS Clinics Australia. No other competing interests were declared.
Contributors: D. Blumberger, P. Fitzgerald and Z. Daskalakis designed the study. D. Blumberger, J. Dimitrova, A. Throop, D. Voineskos and Z. Daskalakis acquired the data, which V. Tang, D. Blumberger, J. Dimitrova, S. McClintock, J. Downer, Y. Knyahnytska, B. Mulsant and Z. Daskalakis analyzed. V. Tang, Y. Knyahnytska and Z. Daskalakis wrote the article, which D. Blumberger, J. Dimitrova, A. Throop, S. McClintock, D. Voineskos, J. Downar, Y. Knyahnytska, B. Mulsant, P. Fitzgerald and Z. Daskalakis reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: Z.J. Daskalakis, Centre for Addiction and Mental Health, 1001 Queen St. W., Toronto, ON M6J 1H4; email@example.com