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Original Investigation |

Indicators for Remission of Suicidal Ideation Following Magnetic Seizure Therapy in Patients With Treatment-Resistant Depression

Yinming Sun, MASc1; Faranak Farzan, PhD1; Benoit H. Mulsant, MD, MS, FRCPC2; Tarek K. Rajji, MD, FRCPC1,2; Paul B. Fitzgerald, MBBS, MPM, PhD, FRANZCP3; Mera S. Barr, PhD1; Jonathan Downar, MD, PhD4; Willy Wong, PhD5; Daniel M. Blumberger, MD, MS, FRCPC1,2; Zafiris J. Daskalakis, MD, PhD, FRCPC1,2
[+] Author Affiliations
1Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
2Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
3Monash Alfred Psychiatry Research Centre, Alfred and Monash University Central Clinical School, Victoria, Australia
4Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario, Canada
5Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada
JAMA Psychiatry. 2016;73(4):337-345. doi:10.1001/jamapsychiatry.2015.3097.
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Importance  Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder.

Objective  To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG).

Design, Setting, and Participants  Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site.

Interventions  The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used.

Main Outcomes and Measures  Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP.

Results  Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex—but not in the motor cortex—were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003).

Conclusions and Relevance  These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.

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Figures

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Figure 1.
Two Transcranial Magnetic Stimulation (TMS) and Electroencephalography Measures of Inhibition

A, The N100 measure was quantified through peak analysis of a single-pulse TMS-evoked potential (TEP) based on equation 1. B, N100 values plotted topographically across all electrodes. C, Long-interval cortical inhibition (LICI), quantified through area comparison of a single- and paired-pulse TEP based on equation 2. D, LICI values plotted topographically across all electrodes. All panels show results from dorsolateral prefrontal cortex stimulation. The TEPs from panels A and C are for electrode FCz, which had the largest N100 and LICI magnitude for the patients in this study. Panels B and D show that both N100 and LICI have frontal topography. Min indicates minimum.

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Figure 2.
Correlation Between Baseline N100 and Long-Interval Cortical Inhibition (LICI) Measures and Changes in Suicidal Ideation on the Scale for Suicide Ideation (SSI)

A greater decrease in the SSI score is associated with a more negative baseline N100 value (FC4 electrode) (A) and a greater baseline LICI value (FC6 electrode) (B). Although the magnitudes of N100 and LICI values are largest over the frontal central region (Figure 1), the correlations are most significant over the right frontal cortex: N100 (C) and LICI (D).

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Figure 3.
Indication of Remission of Suicidal Ideation Using N100 and Long-Interval Cortical Inhibition (LICI)

Receiver operating characteristic (ROC) curve for indication of remission of suicidal ideation (defined as having a pretreatment score of ≥1 and a posttreatment score of 0 on the Scale for Suicide Ideation). A, The ROC curve with N100 as the only indicator. B, The ROC curve with both N100 and LICI as indicators. C, Plots of the accuracy of the indication based on different threshold values for N100, LICI, and a combination of these 2 measures of cortical inhibition.

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