Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: An analysis from the randomised non-inferiority THREE-D trial

Alisson P Trevizol, Jonathan Downar, Fidel Vila-Rodriguez, Kevin E Thorpe, Zafiris J Daskalakis, Daniel M Blumberger, Alisson P Trevizol, Jonathan Downar, Fidel Vila-Rodriguez, Kevin E Thorpe, Zafiris J Daskalakis, Daniel M Blumberger

Abstract

Background: Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), treatment selection is still mainly a process of trial-and-error. The present study aimed to identify clinical predictors of remission after a course of rTMS delivered to the left DLPFC to improve patient selection.

Methods: Data from a large randomised non-inferiority trial comparing standard 10 Hz and intermittent theta burst stimulation (iTBS) for the treatment of MDD were used for the exploratory analyses. Individual variables were assessed for their association with remission and then included in a logistic regression model to determine odds ratios (OR) and corresponding 95% confidence intervals. Model discrimination (internal validation) was carried out to assess model optimism using the c-index. ClinicalTrials.gov identifier: NCT01887782.

Findings: 388 subjects were included in the analysis (199-iTBS and 189-10 Hz, respectively). Higher baseline severity of both depressive and anxiety symptoms were associated with a lower chance of achieving remission (OR=0.64, 95% CI 0.46-0.88; and 0.78, 95% CI 0·60-0.98, respectively). Current employment was a positive predictor for remission (OR=1.69, 95% CI 1.06-2.7), while greater number of treatment failures was associated with lower odds of achieving remission (OR=0.51, 95% CI 0.27-0.98). A non-linear effect of age and remission was observed. An analysis to allow an estimate of the probability of remission using all variables was assessed. The c-index for the fitted model was 0.687.

Interpretation: Our results suggest that measuring depression symptom severity, employment status, and refractoriness are important in prognosticating outcome to a course of rTMS in MDD.

Funding: Canadian Institutes of Health Research MOP-136801.

Keywords: Brain stimulation; Intermittent theta burst stimulation; Major depressive disorder; Repetitive transcranial magnetic stimulation.

Conflict of interest statement

Dr. Downar reports non-financial support from Brainsway Inc., non-financial support from Magventure Inc., grants from Arrell Family Foundation, grants from Buchan Family Foundation, grants from Canadian Biomarker Integration Network in Depression, grants from Canadian Institutes of Health Research (CIHR), grants from Klarman Family Foundation, grants from National Institute of Mental Health, grants from Ontario Brain Institute, grants from Weston Family Foundation, personal fees from Lundbeck, personal fees from ANT Neuro, personal fees from BrainCheck, personal fees from Restorative Brain Clinics, personal fees from TMS Neuro Solutions, during the conduct of the study. Dr. Vila-Rodriguez reports grants from Canadian Institutes of Health Research, grants from Brain Canada, grants from Vancouver Coastal Health Research Institute, grants from Michael Smith Foundation for Health Research, personal fees from Janssen Pharmaceuticals, non-financial support from Magventure, during the conduct of the study. Dr. Daskalakis reports non-financial support from Brainsway Inc., non-financial support from Magventure Inc., grants from Ontario Mental Health Foundation (OMHF), grants from Canadian Institutes of Health Research (CIHR), grants from National Institutes of Mental Health (NIMH), grants from Temerty Family, grants from Grant Family, grants from Centre for Addiction and Mental Health (CAMH) Foundation, grants from Campbell Institute, during the conduct of the study. Dr. Blumberger reports grants from Brain Canada, grants from Canadian Institutes of Health Research, grants from Weston Brain Institute, grants from Centre for Addiction and Mental Health (CAMH) Foundation, grants from Campbell Institute, non-financial support from Brainsway, non-financial support from Indivior, other from Janssen, grants from National Institute of Health, during the conduct of the study. All the other authors do not have any conflicts of interest to declare.

© 2020 The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT flow diagram.
Fig. 2
Fig. 2
Non-linear age effect demonstrated by the shape of the relationship on the log-odds (a) and probability (b) scales.

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