Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial

Abstract Background With 30%–50% of people with bipolar depression (BDep) not responding to multiple pharmacological treatments, alternative therapies are needed. Accelerated intermittent theta burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (L‐DLPFC) has been employed for ind...

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Main Authors: Taro Kishi, Kenji Sakuma, Shun Hamanaka, Yasufumi Nishii, Kosei Esaki, Yueren Zhao, Yuki Matsuda, Shinsuke Kito, Nakao Iwata
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:PCN Reports
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Online Access:https://doi.org/10.1002/pcn5.70064
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author Taro Kishi
Kenji Sakuma
Shun Hamanaka
Yasufumi Nishii
Kosei Esaki
Yueren Zhao
Yuki Matsuda
Shinsuke Kito
Nakao Iwata
author_facet Taro Kishi
Kenji Sakuma
Shun Hamanaka
Yasufumi Nishii
Kosei Esaki
Yueren Zhao
Yuki Matsuda
Shinsuke Kito
Nakao Iwata
author_sort Taro Kishi
collection DOAJ
description Abstract Background With 30%–50% of people with bipolar depression (BDep) not responding to multiple pharmacological treatments, alternative therapies are needed. Accelerated intermittent theta burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (L‐DLPFC) has been employed for individuals with pharmacological treatment‐resistant major depressive disorder (TR‐MDD). Imaging studies have revealed reduced regional activity of the L‐DLPFC for both TR‐MDD and pharmacological treatment‐resistant BDep (TR‐BDep), suggesting that aiTBS over the L‐DLPFC may be beneficial for people with TR‐BDep. Methods A 6‐week, double‐blind, sham‐controlled, randomized trial will be conducted to compare the efficacy and safety of aiTBS to the L‐DLPFC in people with TR‐BDep (jRCTs042240019). Fifty iTBS sessions (1800 pulses/session) will be delivered in 10 daily sessions over 5 consecutive days at 90% resting motor threshold. This aiTBS protocol is termed as Fujita Neuromodulation Therapy for Bipolar Depression (FNT‐BD). Twenty‐two participants (both sexes, aged 18–64 years) with TR‐BDep (DSM‐5‐TR, Type I) will be recruited. The response rate at any given week of follow‐up will be the primary efficacy outcome, defined as a reduction of ≥50% in the Montgomery Åsberg Depression Rating Scale (MADRS) score. Other outcomes will include MADRS score changes, remission rate (10 ≥ MADRS score), Clinical Global Impression‐Improvement score, Clinical Global Impression‐Severity score, discontinuation rate, and incidence of individual adverse events. Results We anticipate that individuals who receive the aiTBS treatment show significant improvement in depressing symptoms compared to those receiving sham treatment. Conclusions This study will provide valuable evidence for both patients with TR‐BDep and clinicians.
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spelling doaj-art-5fbc354c3a714487a02f38caee301a7c2025-08-20T03:40:30ZengWileyPCN Reports2769-25582025-03-0141n/an/a10.1002/pcn5.70064Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trialTaro Kishi0Kenji Sakuma1Shun Hamanaka2Yasufumi Nishii3Kosei Esaki4Yueren Zhao5Yuki Matsuda6Shinsuke Kito7Nakao Iwata8Department of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Development and Education of Clinical Research Fujita Health University School of Medicine Toyoake Aichi JapanDepartment of Psychiatry Jikei University School of Medicine Minato‐ku Tokyo JapanDepartment of Psychiatry Fujita Health University School of Medicine Toyoake Aichi JapanAbstract Background With 30%–50% of people with bipolar depression (BDep) not responding to multiple pharmacological treatments, alternative therapies are needed. Accelerated intermittent theta burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (L‐DLPFC) has been employed for individuals with pharmacological treatment‐resistant major depressive disorder (TR‐MDD). Imaging studies have revealed reduced regional activity of the L‐DLPFC for both TR‐MDD and pharmacological treatment‐resistant BDep (TR‐BDep), suggesting that aiTBS over the L‐DLPFC may be beneficial for people with TR‐BDep. Methods A 6‐week, double‐blind, sham‐controlled, randomized trial will be conducted to compare the efficacy and safety of aiTBS to the L‐DLPFC in people with TR‐BDep (jRCTs042240019). Fifty iTBS sessions (1800 pulses/session) will be delivered in 10 daily sessions over 5 consecutive days at 90% resting motor threshold. This aiTBS protocol is termed as Fujita Neuromodulation Therapy for Bipolar Depression (FNT‐BD). Twenty‐two participants (both sexes, aged 18–64 years) with TR‐BDep (DSM‐5‐TR, Type I) will be recruited. The response rate at any given week of follow‐up will be the primary efficacy outcome, defined as a reduction of ≥50% in the Montgomery Åsberg Depression Rating Scale (MADRS) score. Other outcomes will include MADRS score changes, remission rate (10 ≥ MADRS score), Clinical Global Impression‐Improvement score, Clinical Global Impression‐Severity score, discontinuation rate, and incidence of individual adverse events. Results We anticipate that individuals who receive the aiTBS treatment show significant improvement in depressing symptoms compared to those receiving sham treatment. Conclusions This study will provide valuable evidence for both patients with TR‐BDep and clinicians.https://doi.org/10.1002/pcn5.70064accelerated intermittent theta burst stimulationbipolar depressiondouble‐blindefficacyrandomized sham‐controlled trialsafety
spellingShingle Taro Kishi
Kenji Sakuma
Shun Hamanaka
Yasufumi Nishii
Kosei Esaki
Yueren Zhao
Yuki Matsuda
Shinsuke Kito
Nakao Iwata
Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial
PCN Reports
accelerated intermittent theta burst stimulation
bipolar depression
double‐blind
efficacy
randomized sham‐controlled trial
safety
title Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial
title_full Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial
title_fullStr Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial
title_full_unstemmed Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial
title_short Accelerated intermittent theta burst stimulation for pharmacological treatment‐resistant bipolar depression: Protocol for double‐blind, randomized, sham‐controlled trial
title_sort accelerated intermittent theta burst stimulation for pharmacological treatment resistant bipolar depression protocol for double blind randomized sham controlled trial
topic accelerated intermittent theta burst stimulation
bipolar depression
double‐blind
efficacy
randomized sham‐controlled trial
safety
url https://doi.org/10.1002/pcn5.70064
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