Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: an open-label clinical trial

Abstract

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

Conflict of interest statement

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.

© 2020 Joule Inc. or its licensors

Figures

Fig. 1

Consolidated Standards of Reporting Trials (CONSORT) flow diagram for participant enrolment and dropouts.

Fig. 2

(A) Profile plot for individual participants (n = 26) who completed an adequate trial of magnetic seizure therapy (MST; ≥ 8 sessions) on the 24-item Hamilton Rating Scale for Depression (HRSD-24). (B) Group differences on the HRSD-24 pre- and post-MST for participants who completed an adequate trial of MST (n = 26) and those who completed the entire course of treatment (up to 24 sessions or to remission; n = 20).

Fig. 3

Effect sizes for cognitive outcomes presented with Cohen’s d and 95% confidence intervals. AMI-SF = Autobiographical Memory Interview–Short Form; BVMT-R = Brief Visuospatial Memory Test–Revised; Categories–animals = Category Fluency Animal Naming; COWAT = Controlled Oral Word Association Test; HVLT-R = Hopkins Verbal Learning Test–Revised; LNS = Letter Number Span; Mazes = Neuropsychological Assessment Battery–Mazes; MoCA = Montreal Cognitive Assessment; SS forward/ back = Weschler Memory Scale–Spatial Span; Stroop = Stroop Color and Word Test; Symbol coding = Brief Assessment of Cognition in Schizophrenia–Symbol Coding; Trails A/B = Trail Making Test, A or B.