Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial

Desmyter, Stefanie; Duprat, Romain; Baeken, Chris; Autreve, Sara Van; Audenaert, Kurt; Heeringen, Kees van

doi:10.3389/fnhum.2016.00480

Cited by 94 publications

(110 citation statements)

References 31 publications

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“…Repetitive TMS of the prefrontal cortex is one therapeutic option for treatment-resistant depression and it is being investigated for use in various mood and cognitive disorders. In order to reduce treatment time, clinics have been exploring the use of short protocols such as TBS (Cash, Dar, et al, 2017a;Desmyter et al, 2016;Duprat et al, 2016;Li et al, 2014), however limited clinical efficacy has also been reported (Prasser et al, 2015). The present data provide the first evidence that using conventional iTBS may not be optimal for neuromo- (Li et al, 2018;Pellicciari, Ponzo, Caltagirone, & Koch, 2017).…”

Section: Inter-individual Variability In the Response To Conventionmentioning

confidence: 76%

“…In order to reduce treatment time, clinics have been exploring the use of short protocols such as TBS (Cash, Dar, et al, 2017a;Desmyter et al, 2016;Duprat et al, 2016;Li et al, 2014), however limited clinical efficacy has also been reported (Prasser et al, 2015). In order to reduce treatment time, clinics have been exploring the use of short protocols such as TBS (Cash, Dar, et al, 2017a;Desmyter et al, 2016;Duprat et al, 2016;Li et al, 2014), however limited clinical efficacy has also been reported (Prasser et al, 2015).…”

Section: Inter-individual Variability In the Response To Conventionmentioning

confidence: 99%

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The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS‐EEG study

Chung

Sullivan

Rogasch

et al. 2018

Human Brain Mapping

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Recent studies have highlighted variability in response to theta burst stimulation (TBS) in humans. TBS paradigm was originally developed in rodents to mimic gamma bursts coupled with theta rhythms, and was shown to elicit long‐term potentiation. The protocol was subsequently adapted for humans using standardised frequencies of stimulation. However, each individual has different rhythmic firing pattern. The present study sought to explore whether individualised intermittent TBS (Ind iTBS) could outperform the effects of two other iTBS variants. Twenty healthy volunteers received iTBS over left prefrontal cortex using 30 Hz at 6 Hz, 50 Hz at 5 Hz, or individualised frequency in separate sessions. Ind iTBS was determined using theta‐gamma coupling during the 3‐back task. Concurrent use of transcranial magnetic stimulation and electroencephalography (TMS‐EEG) was used to track changes in cortical plasticity. We also utilised mood ratings using a visual analogue scale and assessed working memory via the 3‐back task before and after stimulation. No group‐level effect was observed following either 30 or 50 Hz iTBS in TMS‐EEG. Ind iTBS significantly increased the amplitude of the TMS‐evoked P60, and decreased N100 and P200 amplitudes. A significant positive correlation between neurophysiological change and change in mood rating was also observed. Improved accuracy in the 3‐back task was observed following both 50 Hz and Ind iTBS conditions. These findings highlight the critical importance of frequency in the parameter space of iTBS. Tailored stimulation parameters appear more efficacious than standard paradigms in neurophysiological and mood changes. This novel approach presents a promising option and benefits may extend to clinical applications.

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Section: Inter-individual Variability In the Response To Conventionmentioning

confidence: 76%

Section: Inter-individual Variability In the Response To Conventionmentioning

confidence: 99%

The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS‐EEG study

Chung

Sullivan

Rogasch

et al. 2018

Human Brain Mapping

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“…Due to the rapid induction of modulatory effects compared to conventional rTMS, TBS is an attractive option for neuromodulatory treatments in clinical disorders (Chung et al, ; Machado et al, ). For psychiatric conditions, this typically involves stimulation delivered to prefrontal cortical regions such as dorsolateral prefrontal cortex (DLPFC) (Desmyter et al, ; Li et al, ; Plewnia et al, ). As adoption of TBS increases in the clinical literature, the lack of consensus with respect to optimal intensity is becoming increasingly evident.…”

Section: Introductionmentioning

confidence: 99%

“…Conventionally, TBS in the motor cortex has been applied at 80% of active motor threshold (aMT) (Huang et al, ), equivalent to approximately 70% of resting motor threshold (rMT) (Cardenas‐Morales et al, ; Chen et al, ; Gentner, Wankerl, Reinsberger, Zeller, & Classen, ). Recent reports of the stimulation intensity used in prefrontal TBS for therapeutic intervention have varied quite substantially in the range of 80–120% of rMT (Bakker et al, ; Desmyter et al, ; Duprat et al, ; Li et al, ; Plewnia et al, ; Prasser et al, ). The underlying assumption is that the efficacy of iTBS will be greater with increasing intensity of stimulation.…”

Section: Introductionmentioning

confidence: 99%

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS‐EEG and working memory performance

Chung

Rogasch

Hoy

et al. 2017

Human Brain Mapping

100

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Intermittent theta burst stimulation (iTBS) is a noninvasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex. Sixteen healthy participants received iTBS over prefrontal cortex at either 50, 75 or 100% resting motor threshold in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials and oscillations. The n-back task was used to assess changes in working memory performance. The data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS yielded the largest neurophysiological changes. Improvement in reaction time in the 3-back task was supported by the change in alpha power, however, comparison between conditions revealed no significant differences. The assumption that higher intensity results in greater neuromodulatory effects may be false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.

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“…Individualized functional connectivity-guided targeting, accelerated delivery and high-dose stimulation were predicted to collectively result in higher response and remission rates than FDA-approved TMS protocols. This protocol was termed 'Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)' to distinguish this protocol from other attempts at accelerated iTBS delivery without individualized targeting and/or high dose 26,27 . We recently published a smaller series demonstrating efficacy in a cohort with extremely severe and treatment refractory depression 25 .…”

Section: Introductionmentioning

confidence: 99%

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

Cole

Stimpson

Gulser

et al. 2019

Preprint

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Background: Current treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment which is FDA-approved for treatment-resistant depression. Recent studies suggest several improvements could be made to iTBS by 1) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit, 2) treating with multiple sessions per day at spaced intervals and 3) applying a higher overall pulse dose of stimulation. Objective: Examine the feasibility, tolerability, and preliminary efficacy of an accelerated, highdose, fcMRI-guided iTBS protocol for treatment-resistant depression (TRD) termed 'Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)'. Methods: Thirty-one participants with TRD received open-label SAINT. Resting-state functional connectivity MRI (fcMRI) was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. Results: Twenty-eight of 31 participants (90.32%) met criteria for remission (≤10 on the MADRS) and all 31 were remitted on measures of suicidal ideation. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events. Discussion: Our highly accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatmentresistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.

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Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial

Cited by 94 publications

References 31 publications

The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS‐EEG study

The effects of individualised intermittent theta burst stimulation in the prefrontal cortex: A TMS‐EEG study

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS‐EEG and working memory performance

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

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