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Noda Y, Osawa R, Takeda Y, Fujii K, Saijo Y, Kajiya T, Takeishi K, Moriyama S, Saeki T, Nakajima S, Kitahata R. Left prefrontal intermittent theta-burst stimulation therapy for major depressive disorder: A real-world, multisite observational study in Japan. J Affect Disord 2025; 375:316-323. [PMID: 39892751 DOI: 10.1016/j.jad.2025.01.131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/10/2025] [Accepted: 01/26/2025] [Indexed: 02/04/2025]
Abstract
BACKGROUND Although approved for treatment in 2018, the effectiveness of intermittent theta-burst stimulation (iTBS) in a real-world setting remains inadequately studied. This observational study investigated the real-world use of iTBS, a usual medical practice for depression, factors influencing its effectiveness, and differences in effectiveness between 600 and 1200 pulses. METHODS Data from patients who received iTBS therapy for depression at four private clinics between January 2021 and April 2024 were extracted. Patients were assessed using the 17-item Hamilton Depression Rating Scale at baseline and after treatment completion. Correlation and multiple regression analyses were performed to investigate clinico-demographic factors and stimulation parameters associated with iTBS effectiveness. Safety was assessed using all relevant data, and effectiveness was evaluated using eligible samples. RESULTS Among 538 patients meeting eligibility criteria for effectiveness evaluation (mean age 40.8 ± 13.8 years, 44.1 % women), 63 completed iTBS with 600 pulses, and 475 completed iTBS with 1200 pulses. Overall response and remission rates were 69.1 % and 53.7 %, respectively, with no significant difference in effectiveness between iTBS-600 and iTBS-1200. Multiple regression analysis indicated fewer depressive episodes (β = -0.103, t = -2.080, p = 0.038) and more treatment sessions (β = 0.134, t = 3.155, p = 0.002) may have contributed to the positive effect of iTBS therapy. The most common adverse event was stimulation site pain. No severe adverse events, such as seizure induction or manic switch, were observed. CONCLUSION The results suggest the highly favorable effectiveness of iTBS therapy for major depressive disorder in real-world settings.
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Affiliation(s)
- Yoshihiro Noda
- Shinjuku-Yoyogi Mental Lab Clinic, Tokyo, Japan; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, International University of Health and Welfare, Mita Hospital, Tokyo, Japan.
| | - Ryota Osawa
- Tokyo Yokohama TMS Clinic, Minato-Tokyo, Tokyo, Japan; Tokyo Yokohama TMS Clinic, Kosugi-Kanagawa, Kawasaki, Japan
| | - Yuya Takeda
- Tokyo Yokohama TMS Clinic, Minato-Tokyo, Tokyo, Japan; Tokyo Yokohama TMS Clinic, Kosugi-Kanagawa, Kawasaki, Japan
| | | | - Yuka Saijo
- Tokyo Yokohama TMS Clinic, Minato-Tokyo, Tokyo, Japan; Tokyo Yokohama TMS Clinic, Kosugi-Kanagawa, Kawasaki, Japan
| | - Taku Kajiya
- Tokyo Yokohama TMS Clinic, Kosugi-Kanagawa, Kawasaki, Japan
| | - Kana Takeishi
- Tokyo Yokohama TMS Clinic, Minato-Tokyo, Tokyo, Japan
| | - Sotaro Moriyama
- Shinjuku-Yoyogi Mental Lab Clinic, Tokyo, Japan; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | | | - Shinichiro Nakajima
- Shinjuku-Yoyogi Mental Lab Clinic, Tokyo, Japan; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
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Becker-Sadzio J, Brendel B, Weller S, Bornheimer E, Mehlig U, Padberg F, Vogelmann U, Kammer T, Strube W, Martus P, Fallgatter AJ, Plewnia C. Effectiveness of rTMS compared to SSRI as early treatment of depression - study protocol of a randomized controlled trial (Early-TMS). Eur Arch Psychiatry Clin Neurosci 2025:10.1007/s00406-025-01975-4. [PMID: 39985658 DOI: 10.1007/s00406-025-01975-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 02/05/2025] [Indexed: 02/24/2025]
Abstract
Psychotherapy and antidepressant medication are considered first-line treatment options for major depressive disorder (MDD). However, a high proportion of patients do not respond to initial treatment, underlining the need for alternative treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been established in the treatment of MDD, but the available evidence is limited to forms of MDD with varying degrees of treatment resistance. Randomized-controlled trials (RCT) investigating first-line treatment with rTMS in comparison with first-line antidepressant medication are warranted to further position rTMS within current treatment algorithms for MDD. In this two-stage, therapy response-adapted, randomized multi-center phase 2 rater blinded trial, 106 medication-naïve patients suffering from MDD will be enrolled. In Stage I, participants receive one of the two treatment options for four weeks: either daily bilateral theta burst stimulation (TBS), a patterned and time-saving form of rTMS, or antidepressant medication with selective serotonin reuptake inhibitors (SSRI). The allocation to Stage II occurs therapy response-adapted. Therefore, patients either receive maintenance treatment or will be switched to the respective other treatment arm. Primary outcome is the comparison between the two study arms with regard to therapy response measured by the Montgomery-Asberg Depression Rating Scale (MADRS) after 4 weeks at the end of Stage I. The aim of the study is to provide reliable first evidence and effect size measures of rTMS as first-line treatment compared to SSRI treatment. Positive results will help to implement rTMS in early stages of MDD. Trial registration: ClinicalTrials.gov ID: NCT06545474, August 15, 2024.
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Affiliation(s)
- Julia Becker-Sadzio
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University Hospital Tübingen, Tübingen, Germany
- DZPG (German Center for Mental Health), Berlin, Germany
| | - Bettina Brendel
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University Hospital Tübingen, Tübingen, Germany
- DZPG (German Center for Mental Health), Berlin, Germany
| | - Simone Weller
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University Hospital Tübingen, Tübingen, Germany
- DZPG (German Center for Mental Health), Berlin, Germany
| | - Edmund Bornheimer
- DZPG (German Center for Mental Health), Berlin, Germany
- Lived Experience Representative Early-TMS Study, Tübingen, Germany
| | - Ulrike Mehlig
- DZPG (German Center for Mental Health), Berlin, Germany
- Lived Experience Representative Early-TMS Study, Tübingen, Germany
| | - Frank Padberg
- DZPG (German Center for Mental Health), Berlin, Germany
- Department of Psychiatry and Psychotherapy, LMU University Hospital, Munich, Germany
| | - Ulrike Vogelmann
- DZPG (German Center for Mental Health), Berlin, Germany
- Department of Psychiatry and Psychotherapy, University Hospital, Technical University of Munich (TUM), Munich, Germany
| | - Thomas Kammer
- Section for Neurostimulation, Deptartment of Psychiatry and Psychotherapy III, Ulm University, Ulm, Germany
| | - Wolfgang Strube
- DZPG (German Center for Mental Health), Berlin, Germany
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany
| | - Peter Martus
- DZPG (German Center for Mental Health), Berlin, Germany
- Institute for Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany
| | - Andreas J Fallgatter
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University Hospital Tübingen, Tübingen, Germany
- DZPG (German Center for Mental Health), Berlin, Germany
| | - Christian Plewnia
- Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University Hospital Tübingen, Tübingen, Germany.
- DZPG (German Center for Mental Health), Berlin, Germany.
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Trapp NT, Purgianto A, Taylor JJ, Singh MK, Oberman LM, Mickey BJ, Youssef NA, Solzbacher D, Zebley B, Cabrera LY, Conroy S, Cristancho M, Richards JR, Flood MJ, Barbour T, Blumberger DM, Taylor SF, Feifel D, Reti IM, McClintock SM, Lisanby SH, Husain MM. Consensus review and considerations on TMS to treat depression: A comprehensive update endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol 2025; 170:206-233. [PMID: 39756350 PMCID: PMC11825283 DOI: 10.1016/j.clinph.2024.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 11/13/2024] [Accepted: 12/01/2024] [Indexed: 01/07/2025]
Abstract
This article updates the prior 2018 consensus statement by the National Network of Depression Centers (NNDC) on the use of transcranial magnetic stimulation (TMS) in the treatment of depression, incorporating recent research and clinical developments. Publications on TMS and depression between September 2016 and April 2024 were identified using methods informed by PRISMA guidelines. The NNDC Neuromodulation Work Group met monthly between October 2022 and April 2024 to define important clinical topics and review pertinent literature. A modified Delphi method was used to achieve consensus. 2,396 abstracts and manuscripts met inclusion criteria for review. The work group generated consensus statements which include an updated narrative review of TMS safety, efficacy, and clinical features of use for depression. Considerations related to training, roles/responsibilities of providers, and documentation are also discussed. TMS continues to demonstrate broad evidence for safety and efficacy in treating depression. Newer forms of TMS are faster and potentially more effective than conventional repetitive TMS. Further exploration of targeting methods, use in special populations, and accelerated protocols is encouraged. This article provides an updated overview of topics relevant to the administration of TMS for depression and summarizes expert, consensus opinion on the practice of TMS in the United States.
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Affiliation(s)
- Nicholas T Trapp
- Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
| | - Anthony Purgianto
- Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Joseph J Taylor
- Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Manpreet K Singh
- Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA, USA
| | - Lindsay M Oberman
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA
| | - Brian J Mickey
- Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, USA
| | - Nagy A Youssef
- Pine Rest Christian Mental Health Services, Grand Rapids, MI, USA; Division of Psychiatry and Behavioral Medicine, Michigan State University, Grand Rapids, MI, USA
| | - Daniela Solzbacher
- Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, USA
| | - Benjamin Zebley
- Department of Psychiatry, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, NY, USA
| | - Laura Y Cabrera
- Department of Engineering Science and Mechanics, Center for Neural Engineering, Pennsylvania State University, University Park, PA, USA
| | - Susan Conroy
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mario Cristancho
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
| | - Jackson R Richards
- Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | | | - Tracy Barbour
- Division of Neuropsychiatry and Neuromodulation, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniel M Blumberger
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
| | - Stephan F Taylor
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
| | - David Feifel
- Kadima Neuropsychiatry Institute, La Jolla, CA, USA; University of California-San Diego, San Diego, CA, USA
| | - Irving M Reti
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Shawn M McClintock
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas,TX, USA
| | - Sarah H Lisanby
- Noninvasive Neuromodulation Unit, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA; Division of Translational Research, National Institute of Mental Health, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
| | - Mustafa M Husain
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas,TX, USA; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
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Yang J, Xie G, Yi L, Liang J, Shao Z, Li Q, Huang W, Sun J, Wu K, Xu J. Impact of high-frequency rTMS combined with pharmacotherapy on the left dorsolateral prefrontal cortex in treating major depressive disorder: A real-world study. J Affect Disord 2025; 368:67-72. [PMID: 39271069 DOI: 10.1016/j.jad.2024.09.065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) combined with pharmacotherapy is a promising treatment method for depression. However, its treatment mechanism needs further research. METHODS This study recruited 38 healthy individuals (HC) and 52 patients with severe depression (MDD) and divided patients into two treatment groups: the rTMS combined antidepressant (rTMS+ADP) group and the single antidepressant (ADP) group. We used functional magnetic resonance imaging to calculate the fractional amplitude of low-frequency fluctuations (fALFF) in the left dorsolateral prefrontal cortex (DLPFC) to investigate the functional change after treatment. RESULT The fALFF in the left DLPFC was significantly lower in the MDD group than that in the HC group (p < 0.05). In addition, fALFF values of the left DLPFC negatively correlated with HAMD-24 scores (r = -0.294, p = 0.005). After treatment, both MDD groups showed a significant decrease in HAMD-24 scores, with a response rate of 88.89 % and a remission rate of 62.96 % in the rTMS+ADP group, compared to 64 % response and 56 % remission rates in the ADP group. The fALFF values in patients' left DLPFC significantly reduced in the rTMS+ADP group (p < 0.05), but not in the ADP group. LIMITATIONS Our study only focused on the treatment effect in the left DLPFC, without exploring the other brain regions or networks. CONCLUSIONS This study emphasizes the significance of the left DLPFC in MDD treatment. However, combined left DLPFC rTMS with ADP causes deviation from the normal resting brain function of the left DLPFC, indicating that future research should explore targeted treatment methods to normalize the left DLPFC.
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Affiliation(s)
- Jun Yang
- School of Mechatronic Engineering and Automation, Foshan University, Foshan, China
| | - Guojun Xie
- Department of Psychiatry, The Third People's Hospital of Foshan, Foshan, China; Department of Psychiatry, The Third Affiliated Hospital of Foshan University, Foshan, China
| | - Li Yi
- School of Mechatronic Engineering and Automation, Foshan University, Foshan, China
| | - Jiaquan Liang
- Department of Psychiatry, The Third People's Hospital of Foshan, Foshan, China; Department of Psychiatry, The Third Affiliated Hospital of Foshan University, Foshan, China
| | - Zhiyong Shao
- School of Mechatronic Engineering and Automation, Foshan University, Foshan, China
| | - Qidi Li
- School of Mechatronic Engineering and Automation, Foshan University, Foshan, China
| | - Wei Huang
- Department of Psychiatry, The Third People's Hospital of Foshan, Foshan, China; Department of Psychiatry, The Third Affiliated Hospital of Foshan University, Foshan, China
| | - Jinyan Sun
- School of Medicine, Foshan University, Foshan, China.
| | - Kai Wu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, China.
| | - Jinbing Xu
- Department of Psychiatry, The Third People's Hospital of Foshan, Foshan, China; Department of Psychiatry, The Third Affiliated Hospital of Foshan University, Foshan, China.
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Sharif F, Harmer CJ, Klein-Flügge MC, Tan H. Novel NIBS in psychiatry: Unveiling TUS and TI for research and treatment. Brain Neurosci Adv 2025; 9:23982128251322241. [PMID: 40092509 PMCID: PMC11909681 DOI: 10.1177/23982128251322241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 02/03/2025] [Indexed: 03/19/2025] Open
Abstract
Mental disorders pose a significant global burden and constitute a major cause of disability worldwide. Despite strides in treatment, a substantial number of patients do not respond adequately, underscoring the urgency for innovative approaches. Traditional non-invasive brain stimulation techniques show promise, yet grapple with challenges regarding efficacy and specificity. Variations in mechanistic understanding and reliability among non-invasive brain stimulation methods are common, with limited spatial precision and physical constraints hindering the ability to target subcortical areas often implicated in the disease aetiology. Novel techniques such as transcranial ultrasonic stimulation and temporal interference stimulation have gained notable momentum in recent years, possibly addressing these shortcomings. Transcranial ultrasonic stimulation (TUS) offers exceptional spatial precision and deeper penetration compared with conventional electrical and magnetic stimulation techniques. Studies targeting a diverse array of brain regions have shown its potential to affect neuronal excitability, functional connectivity and symptoms of psychiatric disorders such as major depressive disorder. Nevertheless, challenges such as target planning and addressing acoustic interactions with the skull must be tackled for its widespread adoption in research and potentially clinical settings. Similar to transcranial ultrasonic stimulation, temporal interference (TI) stimulation offers the potential to target deeper subcortical areas compared with traditional non-invasive brain stimulation, albeit requiring a comparatively higher current for equivalent neural effects. Promising yet still sparse research highlights TI's potential to selectively modulate neuronal activity, showing potential for its utility in psychiatry. Overall, recent strides in non-invasive brain stimulation methods like transcranial ultrasonic stimulation and temporal interference stimulation not only open new research avenues but also hold potential as effective treatments in psychiatry. However, realising their full potential necessitates addressing practical challenges and optimising their application effectively.
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Affiliation(s)
- Faissal Sharif
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Catherine J Harmer
- Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
| | - Miriam C. Klein-Flügge
- Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK
- Department of Experimental Psychology, University of Oxford, Oxford, UK
- Wellcome Centre for Integrative Neuroimaging (WIN), Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Huiling Tan
- MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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Hwang YJ, Lee J, Hwang J, Sim H, Kim N, Kim TS. Psychiatric Considerations of Infertility. Psychiatry Investig 2024; 21:1175-1182. [PMID: 39610228 DOI: 10.30773/pi.2024.0239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 10/15/2024] [Indexed: 11/30/2024] Open
Abstract
OBJECTIVE Infertility, the inability to achieve pregnancy within a year despite normal attempts to conceive without contraception, causes psychosocial burden for individuals and couples. This review summarized the interrelationship between infertility and psychological stress and suggested various forms of psychological intervention for infertility. METHODS The PubMed, Google Scholar, and Korean Studies Information Service System databases were searched for English- and Korean-language articles published from 1990 to 2024. RESULTS Infertility leads to emotional distress from diagnosis to treatment. Also, psychological stress affects the trajectory of infertility. This distress may cause psychiatric illnesses, negatively affecting pregnancy. Psychotherapies, psychopharmacotherapies, and biological treatments can be used for the management of psychiatric illnesses in infertile patients. Digital therapeutics also have the potential to be a competitive treatment option. CONCLUSION Regular assessment and management of psychological stress in infertile couples are essential during the course of infertility treatment. Psychological intervention of infertile patients should be implemented according to a personalized plan that completely reflects the individual clinical characteristics.
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Affiliation(s)
- Yoon Jung Hwang
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Junhee Lee
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jihyun Hwang
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyeonhee Sim
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Namwoo Kim
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Tae-Suk Kim
- Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Tubbs A, Vazquez EA. Engineering and Technological Advancements in Repetitive Transcranial Magnetic Stimulation (rTMS): A Five-Year Review. Brain Sci 2024; 14:1092. [PMID: 39595855 PMCID: PMC11591941 DOI: 10.3390/brainsci14111092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 10/24/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
In the past five years, repetitive transcranial magnetic stimulation (rTMS) has evolved significantly, driven by advancements in device design, treatment protocols, software integration, and brain-computer interfaces (BCIs). This review evaluates how these innovations enhance the safety, efficacy, and accessibility of rTMS while identifying key challenges such as protocol standardization and ethical considerations. A structured review of peer-reviewed studies from 2019 to 2024 focused on technological and clinical advancements in rTMS, including AI-driven personalized treatments, portable devices, and integrated BCIs. AI algorithms have optimized patient-specific protocols, while portable devices have expanded access. Enhanced coil designs and BCI integration offer more precise and adaptive neuromodulation. However, challenges remain in standardizing protocols, addressing device complexity, and ensuring equitable access. While recent innovations improve rTMS's clinical utility, gaps in long-term efficacy and ethical concerns persist. Future research must prioritize standardization, accessibility, and robust ethical frameworks to ensure rTMS's sustainable impact.
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Affiliation(s)
- Abigail Tubbs
- Biomedical Engineering, College of Engineering and Mines, University of North Dakota, Grand Forks, ND 58202, USA;
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Goodman MS, Schulze L, Daskalakis ZJ, Konstantinou GN, Mansouri F, Trevizol AP, Blumberger DM, Downar J. Randomised controlled trial comparing different intersession intervals of intermittent theta burst delivered to the dorsal medial prefrontal cortex. BMJ MENTAL HEALTH 2024; 27:e301290. [PMID: 39448077 PMCID: PMC11499886 DOI: 10.1136/bmjment-2024-301290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 09/22/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS) that can be administered in a fraction of the time of standard rTMS. Applying multiple daily iTBS sessions (ie, accelerated iTBS) may enable patients to achieve remission more rapidly. However, questions remain regarding the optimal time interval between treatment sessions. OBJECTIVE The overall aim of this study was to compare the efficacy and tolerability of two accelerated bilateral iTBS protocols (ie, 30-min or 60-min intervals) and a once-daily bilateral iTBS protocol (ie, 0-min interval) while the number of pulses was held constant, in patients with treatment-resistant depression (TRD). METHODS 182 patients with TRD were randomised to receive two sessions per day of bilateral iTBS of the dorsomedial prefrontal cortex (DMPFC) at 60-min, 30-min or 0-min intervals. Sham treatments were delivered using a shielded 'sham coil' which produced the auditory and tactile sensations of stimulation. The primary outcome measure was a change in depression scores on the 17-item Hamilton Rating Scale for Depression (HRSD-17) after 20 days of treatment. RESULTS HRSD-17 scores improved across all groups; however, these improvements did not significantly differ between the three groups after 20 days of treatment. Similarly, response and remission rates did not differ between the treatment groups. CONCLUSIONS These results suggest that contrary to our original hypothesis, implementing a 30-min or 60-min interval between two treatment sessions of DMPFC-iTBS does not lead to a more rapid improvement in symptoms, than once-daily iTBS administration. TRIAL REGISTRATION NUMBER NCT02778035.
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Affiliation(s)
- Michelle S Goodman
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Laura Schulze
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Zafiris J Daskalakis
- Department of Psychiatry, University of California San Diego, La Jolla, California, USA
| | - Gerasimos N Konstantinou
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- University Health Network, Toronto, Ontario, Canada
| | | | - Alisson P Trevizol
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Daniel M Blumberger
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Jonathan Downar
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
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O'Sullivan SJ, Buchanan DM, Batail JMV, Williams NR. Should rTMS be considered a first-line treatment for major depressive episodes in adults? Clin Neurophysiol 2024; 165:76-87. [PMID: 38968909 DOI: 10.1016/j.clinph.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 04/16/2024] [Accepted: 06/10/2024] [Indexed: 07/07/2024]
Abstract
Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy.
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Affiliation(s)
- Sean J O'Sullivan
- Department of Psychiatry and Behavioral Sciences, Dell School of Medicine, Austin, TX, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA. USA.
| | - Derrick M Buchanan
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA. USA
| | - Jean-Marie V Batail
- Pôle Hospitalo-Universitaire de Psychiatrie Adulte, Centre Hospitalier Guillaume Régnier, Rennes, France; Université de Rennes, Rennes, France
| | - Nolan R Williams
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA. USA
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Zaidi A, Shami R, Sewell IJ, Cao X, Giacobbe P, Rabin JS, Goubran M, Hamani C, Swardfager W, Davidson B, Lipsman N, Nestor SM. Antidepressant class and concurrent rTMS outcomes in major depressive disorder: a systematic review and meta-analysis. EClinicalMedicine 2024; 75:102760. [PMID: 39170936 PMCID: PMC11338161 DOI: 10.1016/j.eclinm.2024.102760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 07/04/2024] [Accepted: 07/15/2024] [Indexed: 08/23/2024] Open
Abstract
Background Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). Methods In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). Findings 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of -0.65 [-0.98, -0.31], p = 0.0002, I2 = 66.1%), higher response (OR = 0.97 [0.50, 1.44], p < 0.0001, I2 = 25.33%) and remission rates (OR = 1.04 [0.55, 1.52], p < 0.0001, I2 = 0.00%) than medication with sham rTMS. No additive benefit was found for SNRIs with rTMS (SMD of 0.10 [-0.14, 0.34], p = 0.42, I2 = 0.00%; OR = 0.12 [-0.39, 0.62], p = 0.64, I2 = 0.00%; OR = -0.31 [-0.90, 0.28], p = 0.86, I2 = 39.9%). The overall risk of bias for the included studies ranged from low to high, with 1 study having a high risk of bias. Interpretation The combination of rTMS with SSRIs, but not SNRIs, significantly reduced depression severity, increasing response and remission rates. Some analyses demonstrated high heterogeneity, which was influenced by an SSRI trial with a high effect size. Overall, these results suggest that not all antidepressant combination therapies are alike, and SSRIs should be considered when initiating rTMS. Funding Donald T. Stuss Young Investigator Research Innovation Award from the Sandra Black Centre for Brain Resilience & Recovery and the Harquail Centre for Neuromodulation through the Sunnybrook Foundation.
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Affiliation(s)
- Alina Zaidi
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Rafeya Shami
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Isabella J. Sewell
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Xingshan Cao
- Research Design and Biostatistics, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Peter Giacobbe
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Jennifer S. Rabin
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Department of Neurology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, ON, Canada
| | - Maged Goubran
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Clement Hamani
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Department of Neurosurgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Walter Swardfager
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada
| | - Benjamin Davidson
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Department of Neurosurgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Nir Lipsman
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Neurosurgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Sean M. Nestor
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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Bastiaens J, Brown N, Bermudes RA, Juusola JL, Bravata DM, Marton TF. Utilization and outcomes of transcranial magnetic stimulation and usual care for MDD in a large group psychiatric practice. BMC Psychiatry 2024; 24:497. [PMID: 38982458 PMCID: PMC11234753 DOI: 10.1186/s12888-024-05928-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 06/23/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND General psychiatrists' practice standards vary regarding when to implement transcranial magnetic stimulation (TMS) for care of patients with major depressive disorder (MDD). Furthermore, few studies have examined real-world utilization and clinical outcomes of TMS. This study analyzed data from a large, multi-site psychiatric practice to evaluate utilization and outcomes of TMS as well as usual care (UC) for patients with MDD. METHODS Depression outcomes for TMS and UC among adult patients at a multi-site psychiatric group practice were examined in this retrospective cohort analysis. Patients with a primary diagnosis of MDD, PHQ-9 ≥ 10, and a visit in November 2020 with 6-month follow-up were included and categorized into the TMS or UC cohorts. RESULTS Of 1,011 patients with qualifying PHQ-9 at the baseline visit, 9% (89) received a full course of TMS, and 583 patients receiving UC met study inclusion criteria (339 patients were excluded due to lacking a 6-month follow-up visit or receiving esketamine during the study period). The TMS cohort had higher baseline PHQ-9 than UC (17.9 vs. 15.5, p < .001) and had failed more medication trials (≥ 4 vs. 3.1, p < .001). Mean PHQ-9 decreased by 5.7 points (SD = 6.7, p < .001) in the TMS cohort and by 4.2 points (SD = 6.4, p < .001) in the UC cohort over the study period. Among patients who had failed four or more antidepressant medications, PHQ-9 decreased by 5.8 points in the TMS cohort (SD = 6.7, p < .001) and by 3.2 points in the UC cohort (SD = 6.3, p < .001). CONCLUSIONS TMS utilization was low, despite TMS showing significant real-world clinical benefits. Future research should examine and address barriers to wider adoption of TMS into routine patient care for patients with treatment-resistant MDD. Wider adoption including routine use of TMS in less treatment-resistant patients will allow statistical comparisons of outcomes between TMS and UC populations that are difficult to do when TMS is underutilized.
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Affiliation(s)
- Jesse Bastiaens
- Mindful Health Solutions, 360 Post St #500, San Francisco, CA, 94108, USA
- Department of Psychiatry, University of California, San Francisco, CA, USA
| | - Natalie Brown
- Mindful Health Solutions, 360 Post St #500, San Francisco, CA, 94108, USA
| | - Richard A Bermudes
- Mindful Health Solutions, 360 Post St #500, San Francisco, CA, 94108, USA
- Department of Psychiatry, University of California, San Francisco, CA, USA
| | | | - Dena M Bravata
- Mindful Health Solutions, 360 Post St #500, San Francisco, CA, 94108, USA
- Center for Primary Care & Outcomes Research, Stanford University, Palo Alto, CA, USA
| | - Tobias F Marton
- Mindful Health Solutions, 360 Post St #500, San Francisco, CA, 94108, USA.
- Department of Psychiatry, University of California, San Francisco, CA, USA.
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Galanis C, Neuhaus L, Hananeia N, Turi Z, Jedlicka P, Vlachos A. Axon morphology and intrinsic cellular properties determine repetitive transcranial magnetic stimulation threshold for plasticity. Front Cell Neurosci 2024; 18:1374555. [PMID: 38638302 PMCID: PMC11025360 DOI: 10.3389/fncel.2024.1374555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 03/13/2024] [Indexed: 04/20/2024] Open
Abstract
Introduction Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitates the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge. Methods This study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions. Results We observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. Although morphologies of mouse and rat CA1 neurons showed no significant differences, simulations confirmed that axon morphologies significantly influence individual cell activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10% higher intensity required for the induction of synaptic plasticity in the rat tissue cultures. Conclusion These findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS.
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Affiliation(s)
- Christos Galanis
- Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Lena Neuhaus
- Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Nicholas Hananeia
- 3R-Zentrum Gießen, Justus-Liebig-Universitat Giessen, Giessen, Germany
| | - Zsolt Turi
- Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Peter Jedlicka
- 3R-Zentrum Gießen, Justus-Liebig-Universitat Giessen, Giessen, Germany
| | - Andreas Vlachos
- Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Center BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany
- Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Neacsiu AD, Beynel L, Gerlus N, LaBar KS, Bukhari-Parlakturk N, Rosenthal MZ. An experimental examination of neurostimulation and cognitive restructuring as potential components for Misophonia interventions. J Affect Disord 2024; 350:274-285. [PMID: 38228276 PMCID: PMC11989405 DOI: 10.1016/j.jad.2024.01.120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 12/08/2023] [Accepted: 01/10/2024] [Indexed: 01/18/2024]
Abstract
Misophonia is a disorder of decreased tolerance to certain aversive, repetitive common sounds, or to stimuli associated with these sounds. Two matched groups of adults (29 participants with misophonia and 30 clinical controls with high emotion dysregulation) received inhibitory neurostimulation (1 Hz) over a personalized medial prefrontal cortex (mPFC) target functionally connected to the left insula; excitatory neurostimulation (10 Hz) over a personalized dorsolateral PFC (dlPFC) target; and sham stimulation over either target. Stimulations were applied while participants were either listening or cognitively downregulating emotions associated with personalized aversive, misophonic, or neutral sounds. Subjective units of distress (SUDS) and psychophysiological measurements (e.g., skin conductance response [SCR] and level [SCL]) were collected. Compared to controls, participants with misophonia reported higher distress (∆SUDS = 1.91-1.93, ps < 0.001) when listening to and when downregulating misophonic distress. Both types of neurostimulation reduced distress significantly more than sham, with excitatory rTMS providing the most benefit (Cohen's dSUDS = 0.53; dSCL = 0.14). Excitatory rTMS also enhanced the regulation of emotions associated with misophonic sounds in both groups when measured by SUDS (dcontrol = 1.28; dMisophonia = 0.94), and in the misophonia group alone when measured with SCL (d = 0.20). Both types of neurostimulation were well tolerated. Engaging in cognitive restructuring enhanced with high-frequency neurostimulation led to the lowest misophonic distress, highlighting the best path forward for misophonia interventions.
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Affiliation(s)
- Andrada D Neacsiu
- Duke University School of Medicine, Durham, NC, USA; Center for Misophonia and Emotional Dysregulation, Durham, NC, USA; Brain Stimulation Research Center, Durham, NC, USA.
| | - Lysianne Beynel
- National Institute for Mental Health, Bethesta, DC, USA; Duke University School of Medicine, Durham, NC, USA.
| | | | - Kevin S LaBar
- Duke University, Durham, NC, USA; Duke Institute for Brain Sciences, Durham, NC, USA.
| | - Noreen Bukhari-Parlakturk
- Duke University, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; Duke Institute for Brain Sciences, Durham, NC, USA.
| | - M Zachary Rosenthal
- Duke University, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; Center for Misophonia and Emotional Dysregulation, Durham, NC, USA.
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14
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Citrenbaum C, Corlier J, Ngo D, Vince-Cruz N, Wilson A, Wilke SA, Krantz D, Tadayonnejad R, Ginder N, Levitt J, Lee JH, Leuchter MK, Strouse TB, Corse A, Vyas P, Leuchter AF. Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD). Brain Stimul 2023; 16:1566-1571. [PMID: 37863389 DOI: 10.1016/j.brs.2023.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 10/04/2023] [Accepted: 10/08/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). Two common rTMS protocols, 10 Hz and intermittent theta burst stimulation (iTBS), have comparable rates of efficacy in groups of patients. Recent evidence suggests that some individuals may be more likely to benefit from one form of stimulation than the other. The pretreatment pupillary light reflex (PLR) is significantly associated with response to a full course of rTMS using heterogeneous stimulation protocols. OBJECTIVE To test whether the relationship between pretreatment PLR and early symptom improvement differed between subjects treated with iTBS or 10 Hz stimulation. METHODS PLR was measured in 52 subjects who received solely 10 Hz (n = 35) or iTBS (n = 17) to left dorsolateral prefrontal cortex (DLPFC) for the first ten sessions of their treatment course. Primary outcome measure was the percent change of Inventory of Depressive Symptomatology - Self Report (IDS-SR) from session 1 to session 10. RESULTS There was a positive association between normalized maximum constriction velocity (nMCV) and early improvement in subjects receiving 10 Hz stimulation (R = 0.48, p = 0.004) and a negative association in subjects receiving iTBS (R = -0.52, p = 0.03). ANOVA revealed a significant interaction between nMCV and the type of initial stimulation (p = 0.001). Among subjects with low nMCV, those initially treated with iTBS showed 2.6 times greater improvement after 10 sessions (p = 0.01) than subjects initially receiving 10 Hz stimulation. CONCLUSION nMCV may detect physiologic differences between those likely to benefit from 10 Hz or iTBS treatment. Future studies should examine whether PLR could guide prospective treatment selection.
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Affiliation(s)
- Cole Citrenbaum
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Juliana Corlier
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Doan Ngo
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Nikita Vince-Cruz
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Andrew Wilson
- Cooperative Institute for Research in Environmental Sciences (CIRES), University of Colorado Boulder, Boulder, CO, USA; NOAA National Centers for Environmental Information (NCEI), Boulder, CO, USA
| | - Scott A Wilke
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - David Krantz
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Reza Tadayonnejad
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA; Division of the Humanities and Social Sciences, California Institute of Technology, Pasadena, CA, USA
| | - Nathaniel Ginder
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Jennifer Levitt
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - John H Lee
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Michael K Leuchter
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Thomas B Strouse
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Andrew Corse
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA
| | - Pooja Vyas
- Department of Psychiatry, University of California San Diego, San Diego, CA, USA
| | - Andrew F Leuchter
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90024, USA.
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Galanis C, Neuhaus L, Hananeia N, Turi Z, Jedlicka P, Vlachos A. Axon morphology and intrinsic cellular properties determine repetitive transcranial magnetic stimulation threshold for plasticity. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.09.25.559399. [PMID: 37808716 PMCID: PMC10557586 DOI: 10.1101/2023.09.25.559399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2023]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength and direction, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitating the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge. This study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions. We observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. However, axon morphologies of individual cells played a significant role in determining activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10 % higher intensity required for the induction of synaptic plasticity in the rat tissue cultures. These findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS.
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Prentice A, Barreiros AR, van der Vinne N, Stuiver S, van Dijk H, van Waarde JA, Korgaonkar M, Sack AT, Arns M. Rostral Anterior Cingulate Cortex Oscillatory Power Indexes Treatment-Resistance to Multiple Therapies in Major Depressive Disorder. Neuropsychobiology 2023; 82:373-383. [PMID: 37848013 DOI: 10.1159/000533853] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 08/22/2023] [Indexed: 10/19/2023]
Abstract
INTRODUCTION High rostral anterior cingulate cortex (rACC) activity is proposed as a nonspecific prognostic marker for treatment response in major depressive disorder, independent of treatment modality. However, other studies report a negative association between baseline high rACC activation and treatment response. Interestingly, these contradictory findings were also found when focusing on oscillatory markers, specifically rACC-theta power. An explanation could be that rACC-theta activity dynamically changes according to number of previous treatment attempts and thus is mediated by level of treatment-resistance. METHODS Primarily, we analyzed differences in rACC- and frontal-theta activity in large national cross-sectional samples representing various levels of treatment-resistance and resistance to multimodal treatments in depressed patients (psychotherapy [n = 175], antidepressant medication [AD; n = 106], repetitive transcranial magnetic stimulation [rTMS; n = 196], and electroconvulsive therapy [ECT; n = 41]), and the respective difference between remitters and non-remitters. For exploratory purposes, we also investigated other frequency bands (delta, alpha, beta, gamma). RESULTS rACC-theta activity was higher (p < 0.001) in the more resistant rTMS and ECT patients relative to the less resistant psychotherapy and AD patients (psychotherapy-rTMS: d = 0.315; AD-rTMS: d = 0.320; psychotherapy-ECT: d = 1.031; AD-ECT: d = 1.034), with no difference between psychotherapy and AD patients. This association was even more pronounced after controlling for frontal-theta. Post hoc analyses also yielded effects for delta, beta, and gamma bands. CONCLUSION Our findings suggest that by factoring in degree of treatment-resistance during interpretation of the rACC-theta biomarker, its usefulness in treatment selection and prognosis could potentially be improved substantially in future real-world practice. Future research should however also investigate specificity of the theta band.
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Affiliation(s)
- Amourie Prentice
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands,
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, The Netherlands,
- Synaeda Research, Synaeda Psycho Medisch Centrum, Drachten, The Netherlands,
| | - Ana Rita Barreiros
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Brain Dynamics Centre, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia
| | - Nikita van der Vinne
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, The Netherlands
- Synaeda Research, Synaeda Psycho Medisch Centrum, Drachten, The Netherlands
| | - Sven Stuiver
- Department of Psychiatry, Rijnstate Depression Centre, Arnhem, The Netherlands
- Technical Medical Centre, University of Twente, Enschede, The Netherlands
| | - Hanneke van Dijk
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, The Netherlands
| | | | - Mayuresh Korgaonkar
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Brain Dynamics Centre, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia
| | - Alexander T Sack
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Martijn Arns
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, The Netherlands
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Citrenbaum C, Corlier J, Ngo D, Vince-Cruz N, Wilson A, Wilke S, Krantz D, Tadayonnejad R, Ginder N, Levitt J, Lee JH, Strouse T, Corse A, Vyas P, Leuchter AF. Pretreatment pupillary reactivity is associated with outcome of Repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD). J Affect Disord 2023; 339:412-417. [PMID: 37437737 DOI: 10.1016/j.jad.2023.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 06/02/2023] [Accepted: 07/08/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND Pre-treatment biomarkers for outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD) have proven elusive. One promising family of biomarkers involves the autonomic nervous system (ANS), which is dysregulated in individuals with MDD. METHODS We examined the relationship between the pre-treatment pupillary light reflex (PLR) and rTMS outcome in 51 MDD patients. Outcome was measured as the percent change in the 30-item Inventory of Depressive Symptomatology Self Rated (IDS-SR) score from baseline to treatment 30. RESULTS Patients showed significant improvement with rTMS treatment. There was a significant correlation between baseline pupillary Constriction Amplitude (CA) and clinical improvement over the treatment course (R = 0.41, p = 0.003). LIMITATIONS We examined a limited number of subjects who received heterogeneous treatment protocols. Almost all patients in the study received psychotropic medications concomitant with rTMS treatment. CONCLUSION PLR measured before treatment may be a predictive biomarker for clinical improvement from rTMS in subjects with MDD.
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Affiliation(s)
- Cole Citrenbaum
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Juliana Corlier
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Doan Ngo
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Nikita Vince-Cruz
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Andrew Wilson
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Scott Wilke
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - David Krantz
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Reza Tadayonnejad
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA; Division of the Humanities and Social Sciences, California Institute of Technology, Pasadena, CA, USA
| | - Nathaniel Ginder
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Jennifer Levitt
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - John H Lee
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Thomas Strouse
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | - Andrew Corse
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA
| | | | - Andrew F Leuchter
- TMS Clinical and Research Program, Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA.
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18
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Wang X, Fan X, Zhang L, Liu X, Ji Z. Repetitive transcranial magnetic stimulation in the treatment of middle-aged and elderly major depressive disorder: A randomized controlled trial. Medicine (Baltimore) 2023; 102:e34841. [PMID: 37657019 PMCID: PMC10476736 DOI: 10.1097/md.0000000000034841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 07/28/2023] [Indexed: 09/03/2023] Open
Abstract
BACKGROUND Studies have reported the use of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD). However, most studies focus on antidepressant effect of rTMS, but few on cognitive aspects. The present study aimed to explore the effect of rTMS on BDNF levels and cognitive function in the treatment of middle-aged and elderly MDD. METHODS This was a randomized controlled trial. A total of 120 elderly patients with MDD treated in The Second Affiliated Hospital of Xi'an Medical University from January 2021 to January 2023 were selected as research subjects. The patients were randomly divided into control group (n = 60, patients received simple oral treatment with escitalopram and sham rTMS) and study group (n = 60, patients received oral treatment with escitalopram combined with rTMS) according to the random number table method. We compared the clinical efficacy, serum BDNF levels, and cognitive function between the 2 groups. RESULTS After treatment, the HAMD-17 score in the study group was lower than that in the control group [13.00 (12.00-16.00) vs 17.00 (15.00-19.00), P < .05], and the RBANS score was higher than that in the control group [166.00 (161.25-171.75) vs 133.00 (130.00-136.75), P < .05]. The total effective rate of the research group was 95.0%, which was higher than the 82.0% of the control group (P < .05). The serum BDNF levels [36.00 (33.00-38.00) vs 30.00 (28.00-32.00), P < .05] and MoCA scores [24.00 (22.00-26.75) vs 23.00 (21.00-25.00), P < .05] of the study group were higher than those of the control group. There were no significant adverse reactions during the treatment of both groups. CONCLUSIONS Compared with oral escitalopram alone, repeated transcranial magnetic stimulation in the treatment of middle-aged and elderly patients with major depressive disorder can further improve the efficacy, and can more effectively improve the BDNF level and cognitive function, with ideal safety.
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Affiliation(s)
- Xiaofang Wang
- Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, China
| | - Xiubo Fan
- Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, China
| | - Lihui Zhang
- Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, China
| | - Xin Liu
- Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, China
| | - Zhi Ji
- Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, China
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19
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Lv N, Ajilore OA, Xiao L, Venditti EM, Lavori PW, Gerber BS, Snowden MB, Wittels NE, Ronneberg CR, Stetz P, Barve A, Shrestha R, Dosala S, Kumar V, Eckley TL, Goldstein-Piekarski AN, Smyth JM, Rosas LG, Kannampallil T, Zulueta J, Suppes T, Williams LM, Ma J. Mediating Effects of Neural Targets on Depression, Weight, and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot Randomized Clinical Trial. BIOLOGICAL PSYCHIATRY GLOBAL OPEN SCIENCE 2023; 3:430-442. [PMID: 37519462 PMCID: PMC10382700 DOI: 10.1016/j.bpsgos.2022.03.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/25/2022] [Accepted: 03/24/2022] [Indexed: 12/28/2022] Open
Abstract
Background Integrated treatments for comorbid depression (often with anxiety) and obesity are lacking; mechanisms are poorly investigated. Methods In a mechanistic pilot trial, adults with body mass index ≥30 and Patient Health Questionnaire-9 scores ≥10 were randomized to usual care (n = 35) or an integrated behavioral intervention (n = 71). Changes at 6 months in body mass index and Depression Symptom Checklist-20 scores were co-primary outcomes, and Generalized Anxiety Disorder Scale-7 score was a secondary outcome. Changes at 2 months in the activation and functional connectivity of regions of interest in the negative affect circuit were primary neural targets, and secondary targets were in the cognitive control, default mode, and positive affect circuits. Results Participants were 47.0 years (SD = 11.9 years), 76% women, 55% Black, and 20% Latino. Depression Symptom Checklist-20 (between-group difference, -0.3 [95% CI: -0.6 to -0.1]) and Generalized Anxiety Disorder Scale-7 (-2.9 [-4.7 to -1.1]) scores, but not body mass index, decreased significantly at 6 months in the intervention versus usual care groups. Only Generalized Anxiety Disorder Scale-7 score changes at 6 months significantly correlated with neural target changes at 2 months in the negative affect (anterior insula, subgenual/pregenual anterior cingulate cortex, amygdala) and cognitive control circuits (dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex). Effects were medium to large (0.41-1.18 SDs). Neural target changes at 2 months in the cognitive control circuit only differed by treatment group. Effects were medium (0.58-0.79 SDs). Conclusions Compared with usual care, the study intervention led to significantly improved depression but not weight loss, and the results on neural targets were null for both outcomes. The significant intervention effect on anxiety might be mediated through changes in the cognitive control circuit, but this warrants replication.
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Affiliation(s)
- Nan Lv
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois
| | - Olusola A. Ajilore
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois
| | - Lan Xiao
- Department of Epidemiology and Population Health, Stanford University, Palo Alto, California
| | - Elizabeth M. Venditti
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Philip W. Lavori
- Department of Biomedical Data Science, Stanford University, Palo Alto, California
| | - Ben S. Gerber
- Department of Population and Quantitative Health Sciences, University of Massachusetts, Worcester, Massachusetts
| | - Mark B. Snowden
- Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington
| | - Nancy E. Wittels
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Corina R. Ronneberg
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Patrick Stetz
- Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California
| | - Amruta Barve
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois
| | - Rohit Shrestha
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois
| | - Sushanth Dosala
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois
| | - Vikas Kumar
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Tessa L. Eckley
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, Illinois
| | - Andrea N. Goldstein-Piekarski
- Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California
- MIRECC VISN21, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Joshua M. Smyth
- Departments of Biobehavioral Health and Medicine, Pennsylvania State University, State College, Pennsylvania
| | - Lisa G. Rosas
- Department of Epidemiology and Population Health, Stanford University, Palo Alto, California
| | - Thomas Kannampallil
- Department of Anesthesiology and Institute for Informatics, Washington University School of Medicine, St. Louis, Missouri
| | - John Zulueta
- Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois
| | - Trisha Suppes
- Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California
- MIRECC VISN21, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Leanne M. Williams
- Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California
- MIRECC VISN21, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Jun Ma
- Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
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20
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Ziesel D, Nowakowska M, Scheruebel S, Kornmueller K, Schäfer U, Schindl R, Baumgartner C, Üçal M, Rienmüller T. Electrical stimulation methods and protocols for the treatment of traumatic brain injury: a critical review of preclinical research. J Neuroeng Rehabil 2023; 20:51. [PMID: 37098582 PMCID: PMC10131365 DOI: 10.1186/s12984-023-01159-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 03/13/2023] [Indexed: 04/27/2023] Open
Abstract
BACKGROUND Traumatic brain injury (TBI) is a leading cause of disabilities resulting from cognitive and neurological deficits, as well as psychological disorders. Only recently, preclinical research on electrical stimulation methods as a potential treatment of TBI sequelae has gained more traction. However, the underlying mechanisms of the anticipated improvements induced by these methods are still not fully understood. It remains unclear in which stage after TBI they are best applied to optimize the therapeutic outcome, preferably with persisting effects. Studies with animal models address these questions and investigate beneficial long- and short-term changes mediated by these novel modalities. METHODS In this review, we present the state-of-the-art in preclinical research on electrical stimulation methods used to treat TBI sequelae. We analyze publications on the most commonly used electrical stimulation methods, namely transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS) and vagus nerve stimulation (VNS), that aim to treat disabilities caused by TBI. We discuss applied stimulation parameters, such as the amplitude, frequency, and length of stimulation, as well as stimulation time frames, specifically the onset of stimulation, how often stimulation sessions were repeated and the total length of the treatment. These parameters are then analyzed in the context of injury severity, the disability under investigation and the stimulated location, and the resulting therapeutic effects are compared. We provide a comprehensive and critical review and discuss directions for future research. RESULTS AND CONCLUSION: We find that the parameters used in studies on each of these stimulation methods vary widely, making it difficult to draw direct comparisons between stimulation protocols and therapeutic outcome. Persisting beneficial effects and adverse consequences of electrical simulation are rarely investigated, leaving many questions about their suitability for clinical applications. Nevertheless, we conclude that the stimulation methods discussed here show promising results that could be further supported by additional research in this field.
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Affiliation(s)
- D Ziesel
- Institute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Graz, Austria
| | - M Nowakowska
- Research Unit of Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
| | - S Scheruebel
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics Division, Medical University of Graz, Graz, Austria
| | - K Kornmueller
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics Division, Medical University of Graz, Graz, Austria
| | - U Schäfer
- Research Unit of Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
| | - R Schindl
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics Division, Medical University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
| | - C Baumgartner
- Institute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Graz, Austria
- BioTechMed-Graz, Graz, Austria
| | - M Üçal
- Research Unit of Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
- BioTechMed-Graz, Graz, Austria
| | - T Rienmüller
- Institute of Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Graz, Austria.
- BioTechMed-Graz, Graz, Austria.
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21
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Lv N, Hallihan H, Xiao L, Williams LM, Ajilore OA, Ma J. Association of Changes in Neural Targets and Dietary Outcomes among Patients with Comorbid Obesity and Depression: Post hoc Analysis of ENGAGE-2 Mechanistic Clinical Trial. J Nutr 2023; 153:880-896. [PMID: 36931755 PMCID: PMC10196721 DOI: 10.1016/j.tjnut.2023.01.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 12/06/2022] [Accepted: 01/19/2023] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Disruptions in brain circuits that regulate cognition and emotion can hinder dietary change and weight loss among individuals with obesity and depression. OBJECTIVE The study aimed to investigate whether changes in brain targets in the cognitive control, negative affect, and positive affect circuits after 2-mo problem-solving therapy (PST) predict changes in dietary outcomes at 2 and 6 mo. METHODS Adults with obesity and depression from an academic health system were randomly assigned to receive PST (7-step problem-solving and behavioral activation strategies) over 2 mo or usual care. Seventy participants (mean age = 45.9 ± 11.6 y; 75.7% women, 55.7% Black, 17.1% Hispanic, 20.0% White; mean BMI = 36.5 ± 5.3 kg/m2; mean Patient Health Questionnaire-9 depression score = 12.7 ± 2.8) completed functional MRI and 24-h food recalls. Ordinary least square regression analyses were performed. RESULTS Among intervention participants, increased left dorsal lateral prefrontal cortex (dLPFC) activity of the cognitive control circuit at 2 mo was associated with increased diet quality (β: 0.20; 95% CI: -0.02, 0.42) and decreased calories (β: -0.19; 95% CI: -0.33, -0.04), fat levels (β: -0.22; 95% CI: -0.39, -0.06), and high-sugar food intake (β: -0.18; 95% CI: -0.37, 0.01) at 6 mo. For the negative affect circuit, increased right dLPFC-amygdala connectivity at 2 mo was associated with increased diet quality (β: 0.32; 95% CI: -0.93, 1.57) and fruit and vegetable intake (β: 0.38; 95% CI: -0.75, 1.50) and decreased calories (β: -0.37; 95% CI: -1.29, 0.54), fat levels (β: -0.37; 95% CI: -1.50, 0.76), sodium concentrations (β: -0.36; 95% CI: -1.32, 0.60), and alcohol intake (β: -0.71; 95% CI: -2.10, 0.68) at 2 but not at 6 mo. The usual care group showed opposing associations. The 95% CIs of all between-group differences did not overlap the null, suggesting a significant treatment effect. CONCLUSIONS Among adults with obesity and depression who underwent PST compared with those under usual care, improved dLPFC-amygdala regulation of negative affective brain states predicted dietary improvements at 2 mo, whereas improvements in dLPFC-based cognitive control predicted dietary improvements at 6 mo. These findings warrant confirmatory studies. This trial was at clinicaltrials.gov as NCT03841682.
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Affiliation(s)
- Nan Lv
- Department of Medicine, University of Illinois Chicago, Chicago, IL, USA
| | - Hagar Hallihan
- Department of Medicine, University of Illinois Chicago, Chicago, IL, USA
| | - Lan Xiao
- Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA
| | - Leanne M Williams
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Olusola A Ajilore
- Department of Psychiatry, University of Illinois Chicago, Chicago, IL, USA
| | - Jun Ma
- Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
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22
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Cohen SE, Zantvoord JB, Wezenberg BN, Daams JG, Bockting CLH, Denys D, van Wingen GA. Electroencephalography for predicting antidepressant treatment success: A systematic review and meta-analysis. J Affect Disord 2023; 321:201-207. [PMID: 36341804 DOI: 10.1016/j.jad.2022.10.042] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 10/19/2022] [Accepted: 10/22/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Patients suffering from major depressive disorder (MDD) regularly experience non-response to treatment for their depressive episode. Personalized clinical decision making could shorten depressive episodes and reduce patient suffering. Although no clinical tools are currently available, machine learning analysis of electroencephalography (EEG) shows promise in treatment response prediction. METHODS With a systematic review and meta-analysis, we evaluated the accuracy of EEG for individual patient response prediction. Importantly, we included only prediction studies that used cross-validation. We used a bivariate model to calculate prediction success, as expressed by area-under the curve, sensitivity and specificity. Furthermore, we analyzed prediction success for separate antidepressant interventions. RESULTS 15 studies with 12 individual patient samples and a total of 479 patients were included. Research methods varied considerably between studies. Meta-analysis of results from this heterogeneous set of studies resulted in an area under the curve of 0.91, a sensitivity of 83 % (95 % CI 74-89 %), and a specificity of 86 % (95 % CI 81-90 %). Classification performance did not significantly differ between treatments. Although studies were all internally validated, no externally validated studies have been reported. We found substantial risk of bias caused by methodological shortcomings such as non-independent feature selection, though performance of non-biased studies was comparable. LIMITATIONS Sample sizes were relatively small and no study used external validation, increasing the risk of overestimation of accuracy. CONCLUSIONS Electroencephalography can predict the response to antidepressant treatment with high accuracy. However, future studies with more rigorous validation are needed to produce a clinical tool to guide interventions in MDD. PROSPERO REGISTRATION NUMBER CRD42021268169.
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Affiliation(s)
- S E Cohen
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - J B Zantvoord
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - B N Wezenberg
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - J G Daams
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - C L H Bockting
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - D Denys
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - G A van Wingen
- Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands.
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23
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Early augmentation by using neuromodulation in psychiatric disorder: a kaleidoscopic view. CNS Spectr 2022; 27:530-532. [PMID: 33632361 DOI: 10.1017/s1092852921000237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Early augmentation is a relatively newer concept in the management of psychiatric disorders. In managing psychiatric disorders, augmentation strategies are commonly used after failed attempts of optimization of a dose of the medications and then switching to another medication. Neuromodulation methods are recommended by traditional treatment recommendations as augmenting strategies (mostly) in managing treatment-resistant/refractory cases of psychiatric disorders. Late in the process of therapy, several of these techniques are applied to the patient. However, using different neuromodulation techniques, early augmentation of the ongoing pharmacological or psychological treatment may be achieved, resulting in early symptom reduction or remission and early return to work by resuming functionality. The length of the symptomatic cycle may be shortened by early augmentation. There are several potential challenges to adopting an early augmentation strategy in clinical practice. This article discusses the concept and evidence of early augmentation strategy in managing psychiatric disorder by using neuromodulation technique and potential challenges before it.
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24
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Meijs H, Prentice A, Lin BD, De Wilde B, Van Hecke J, Niemegeers P, van Eijk K, Luykx JJ, Arns M. A polygenic-informed approach to a predictive EEG signature empowers antidepressant treatment prediction: A proof-of-concept study. Eur Neuropsychopharmacol 2022; 62:49-60. [PMID: 35896057 DOI: 10.1016/j.euroneuro.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 07/05/2022] [Accepted: 07/08/2022] [Indexed: 11/04/2022]
Abstract
The treatment of major depressive disorder (MDD) is hampered by low chances of treatment response in each treatment step, which is partly due to a lack of firmly established outcome-predictive biomarkers. Here, we hypothesize that polygenic-informed EEG signatures may help predict antidepressant treatment response. Using a polygenic-informed electroencephalography (EEG) data-driven, data-reduction approach, we identify a brain network in a large cohort (N=1,123), and discover it is sex-specifically (male patients, N=617) associated with polygenic risk score (PRS) of antidepressant response. Subsequently, we demonstrate in three independent datasets the utility of the network in predicting response to antidepressant medication (male, N=232) as well as repetitive transcranial magnetic stimulation (rTMS) and concurrent psychotherapy (male, N=95). This network significantly improves a treatment response prediction model with age and baseline severity data (area under the curve, AUC=0.623 for medicaton; AUC=0.719 for rTMS). A predictive model for MDD patients, aimed at increasing the likelihood of being a responder to antidepressants or rTMS and concurrent psychotherapy based on only this network, yields a positive predictive value (PPV) of 69% for medication and 77% for rTMS. Finally, blinded out-of-sample validation of the network as predictor for psychotherapy response in another independent dataset (male, N=50) results in a within-subsample response rate of 50% (improvement of 56%). Overall, the findings provide a first proof-of-concept of a combined genetic and neurophysiological approach in the search for clinically-relevant biomarkers in psychiatric disorders, and should encourage researchers to incorporate genetic information, such as PRS, in their search for clinically relevant neuroimaging biomarkers.
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Affiliation(s)
- Hannah Meijs
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands; GGNet Mental Health, Warnsveld, the Netherlands.
| | - Amourie Prentice
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands; Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands
| | - Bochao D Lin
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Bieke De Wilde
- Department of Psychiatry, Ziekenhuis Netwerk Antwerpen (ZNA), Antwerp, Belgium
| | - Jan Van Hecke
- Department of Psychiatry, Ziekenhuis Netwerk Antwerpen (ZNA), Antwerp, Belgium
| | - Peter Niemegeers
- Department of Psychiatry, Ziekenhuis Netwerk Antwerpen (ZNA), Antwerp, Belgium
| | - Kristel van Eijk
- Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands
| | - Jurjen J Luykx
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands; GGNet Mental Health, Warnsveld, the Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Martijn Arns
- Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands; Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands
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25
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The Association Between Sample and Treatment Characteristics and the Efficacy of Repetitive Transcranial Magnetic Stimulation in Depression: A Meta-analysis and Meta-regression of Sham-controlled Trials. Neurosci Biobehav Rev 2022; 141:104848. [PMID: 36049675 DOI: 10.1016/j.neubiorev.2022.104848] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 08/23/2022] [Accepted: 08/26/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive neuromodulation that is increasingly used to treat major depressive disorder (MDD). However, treatment with rTMS could be optimized by identifying optimal treatment parameters or characteristics of patients that are most likely to benefit. This meta-analysis and meta-regression aims to identify sample and treatment characteristics that are associated with change in depressive symptom level, treatment response and remission. METHODS The databases PubMed, Embase, Web of Science and Cochrane library were searched for randomized controlled trials (RCTs) reporting on the therapeutic efficacy of high-frequent, low-frequent, or bilateral rTMS for MDD compared to sham. Study and sample characteristics as well as rTMS parameters and outcome variables were extracted. Effect sizes were calculated for change in depression score and risk ratios for response and remission. RESULTS Sixty-five RCTs with a total of 2982 subjects were included in this meta-analysis. Active rTMS resulted in a larger depressive symptom reduction than sham protocol (Hedges' g = -0.791 95% CI -0.977; -0.605). Risk ratios for response and remission were 2.378 (95% CI 1.882; 3.005) and 2.450 (95% CI 1.779; 3.375), respectively. We found no significant association between sample and treatment parameters and rTMS efficacy. CONCLUSIONS rTMS is an efficacious treatment for MDD. No associations between sample or treatment characteristics and efficacy were found, for which we caution that publication bias, heterogeneity and lack of consistency in the definition of remission might bias these latter null findings. Our results are clinically relevant and support the use of rTMS as a non-invasive and effective treatment option for depression.
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26
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Fitzgerald PB, George MS, Pridmore S. The evidence is in: Repetitive transcranial magnetic stimulation is an effective, safe and well-tolerated treatment for patients with major depressive disorder. Aust N Z J Psychiatry 2022; 56:745-751. [PMID: 34459284 DOI: 10.1177/00048674211043047] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Despite more than 25 years of research establishing the antidepressant efficacy of repetitive transcranial magnetic stimulation, there remains uncertainty about the depth and breadth of this evidence base, resulting in confusion as to where repetitive transcranial magnetic stimulation fits in the therapeutic armamentarium in the management of patients with mood disorders. The purpose of this article is to provide a concise description of the evidence base supporting the use of repetitive transcranial magnetic stimulation in the context of the stages of research that typically accompanies the development of evidence for a new therapy. The antidepressant efficacy for the use of repetitive transcranial magnetic stimulation in the treatment of depression has been established through a relatively traditional pathway beginning with small case series, progressing to single-site clinical trials and then to larger multisite randomised double-blind controlled trials. Antidepressant effects have been confirmed in numerous meta-analyses followed more recently by large network meta-analysis and umbrella reviews, with evidence that repetitive transcranial magnetic stimulation may have greater efficacy than alternatives for patients with treatment-resistant depression. Finally, repetitive transcranial magnetic stimulation has been shown to produce meaningful response and remission rates in real-world samples of greater than 5000 patients. The evidence for the antidepressant efficacy of repetitive transcranial magnetic stimulation therapy is overwhelming, and it should be considered a routine part of clinical care wherever available.
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Affiliation(s)
- Paul B Fitzgerald
- Epworth Centre for Innovation in Mental Health, Epworth Healthcare, Camberwell, VIC, Australia.,Department of Psychiatry, Monash University, Melbourne, VIC, Australia
| | - Mark S George
- The Brain Stimulation Laboratory, Medical University of South Carolina, Charleston, SC, USA.,Ralph H. Johnson VA Medical Center, Charleston, SC, USA
| | - Saxby Pridmore
- Discipline of Psychiatry, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia
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27
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Hebel T, Grözinger M, Landgrebe M, Padberg F, Schecklmann M, Schlaepfer T, Schönfeldt-Lecuona C, Ullrich H, Zwanzger P, Langguth B, Bajbouj M, Bewernick B, Brinkmann K, Cordes J, Di Pauli J, Eichhammer P, Freundlieb N, Hajak G, Höppner-Buchmann J, Hurlemann R, Kamp D, Kayser S, Kis B, Kreuzer PM, Kuhn J, Lammers M, Lugmayer B, Mielacher C, Nickl-Jockschat T, Nunhofer C, Palm U, Poeppl TB, Polak T, Sakreida K, Sartorius A, Silberbauer C, Zilles-Wegner D. Evidence and expert consensus based German guidelines for the use of repetitive transcranial magnetic stimulation in depression. World J Biol Psychiatry 2022; 23:327-348. [PMID: 34668449 DOI: 10.1080/15622975.2021.1995810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field. METHODS The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations. FINDINGS Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.
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Affiliation(s)
- Tobias Hebel
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - Michael Grözinger
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH University, Aachen, Germany
| | - Michael Landgrebe
- Department of Psychiatry, Kbo-Lech-Mangfall Clinic, Agatharied, Germany
| | - Frank Padberg
- Department of Psychiatry and Psychotherapy, LMU University Munich, Munich, Germany
| | - Martin Schecklmann
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - Thomas Schlaepfer
- Department of Psychiatry and Psychotherapy, Interventional Biological Psychiatry, University Freiburg, Freiburg, Germany
| | | | - Heiko Ullrich
- Department of Psychiatry, Psychotherapy and Psychosomatics, Siegen Hospital, Siegen, Germany
| | - Peter Zwanzger
- Department of Psychiatry and Psychotherapy, LMU University Munich, Munich, Germany.,Clinical Center for Psychiatry, Psychotherapy, Psychosomatic Medicine, Geriatrics and Neurology, Kbo-Inn-Salzach-Klinikum, Wasserburg/Inn, Germany
| | - Berthold Langguth
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | | | | | - Bettina Bewernick
- Departments of Geriatric Psychiatry, Psychiatry, and Psychotherapy, University Hospital Bonn, Bonn, Germany
| | - Klaus Brinkmann
- Center for Psychosocial Medicine, Agaplesion Diakonieklinikum Hospital Rotenburg, Rotenburg, Germany
| | - Joachim Cordes
- Department of Psychiatry and Psychotherapy, Kaiserswerther Diakonie, Düsseldorf, Germany
| | - Jan Di Pauli
- Department of Adult Psychiatry, Rankweil Hospital, Vocklabruck, Austria
| | - Peter Eichhammer
- Clinic for Mental Health, Goldener Steig Hospital, Freyung, Germany
| | - Nils Freundlieb
- Department of Psychiatry and Psychotherapy, Center for Psychosocial Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Göran Hajak
- Department of Psychiatry and Psychotherapy, Sozialstiftung, Bamberg, Germany
| | - Jacqueline Höppner-Buchmann
- Department of Geriatric Psychiatry and Psychotherapy, Helios Hospital Schwerin, Carl-Friedrich-Flemming Hospital, Schwerin, Germany
| | - Rene Hurlemann
- Department of Psychiatry and Psychotherapy, Karl-Jaspers Hospital, University Oldenburg, Bad Zwischenahn, Germany
| | - Daniel Kamp
- Department of Psychiatry and Psychotherapy, LVR Hospital, Heinrich-Heine University, Düsseldorf, Germany
| | - Sarah Kayser
- Department of General Psychiatry, Psychotherapy and Psychosomatics 3/Geriatric Psychiatry, Rheinhessen Hospital Alzey, Alzey, Germany
| | - Bernhard Kis
- Department of Psychiatry, Psychotherapy and Psychosomatics, Catholic Hospitals Ruhrhalbinsel, Hattingen, Germany
| | - Peter M Kreuzer
- Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - Jens Kuhn
- Department of Psychiatry, Psychotherapy and Psychosomatics, Johanniter Hospital Oberhausen, Oberhausen, Germany
| | - Melisande Lammers
- Hospital for Psychosomatics and Psychotherapy, MediClin Reichshof Hospital, Reichshof-Eckenhagen, Germany
| | - Beatrix Lugmayer
- Department of Psychiatry, Salzkammergut Hospital Vöcklabruck, Vocklabruck, Austria
| | - Clemens Mielacher
- Department of Psychiatry and Psychotherapy, Section Clinical Psychology, University Hospital Bonn, Bonn, Germany
| | - Thomas Nickl-Jockschat
- Departments of Psychiatry, Neuroscience and Pharmacology, Iowa Neuroscience Institute Carver College of Medicine University of Iowa, Iowa City, IA, USA
| | - Christian Nunhofer
- Private Practice in Neurology, Psychiatry and Psychotherapy, Neumarkt, Germany
| | - Ulrich Palm
- Medical Park Chiemseeblick, Bernau-Felden, Germany
| | - Timm B Poeppl
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH University, Aachen, Germany
| | - Thomas Polak
- Department and Clinic of Psychiatry, Psychosomatics and Psychotherapy, Neurovascular Functional Diagnostics, Center for Mental Health, Würzburg University Hospital, Wuerzburg, Germany
| | - Katrin Sakreida
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH University, Aachen, Germany
| | - Alexander Sartorius
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
| | | | - David Zilles-Wegner
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Georg-August University, Göttingen, Germany
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Somaa FA, de Graaf TA, Sack AT. Transcranial Magnetic Stimulation in the Treatment of Neurological Diseases. Front Neurol 2022; 13:793253. [PMID: 35669870 PMCID: PMC9163300 DOI: 10.3389/fneur.2022.793253] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 02/25/2022] [Indexed: 12/16/2022] Open
Abstract
Transcranial Magnetic Stimulation (TMS) has widespread use in research and clinical application. For psychiatric applications, such as depression or OCD, repetitive TMS protocols (rTMS) are an established and globally applied treatment option. While promising, rTMS is not yet as common in treating neurological diseases, except for neurorehabilitation after (motor) stroke and neuropathic pain treatment. This may soon change. New clinical studies testing the potential of rTMS in various other neurological conditions appear at a rapid pace. This can prove challenging for both practitioners and clinical researchers. Although most of these neurological applications have not yet received the same level of scientific/empirical scrutiny as motor stroke and neuropathic pain, the results are encouraging, opening new doors for TMS in neurology. We here review the latest clinical evidence for rTMS in pioneering neurological applications including movement disorders, Alzheimer's disease/mild cognitive impairment, epilepsy, multiple sclerosis, and disorders of consciousness.
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Affiliation(s)
- Fahad A. Somaa
- Department of Occupational Therapy, Faculty of Medical Rehabilitation, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Tom A. de Graaf
- Section Brain Stimulation and Cognition, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
- Center of Integrative Neuroscience, Maastricht University, Maastricht, Netherlands
| | - Alexander T. Sack
- Section Brain Stimulation and Cognition, Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
- Center of Integrative Neuroscience, Maastricht University, Maastricht, Netherlands
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Brain + Nerve Centre, Maastricht University Medical Centre+, Maastricht, Netherlands
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29
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Transdiagnostic Symptom Subtypes to Predict Response to Therapeutic Transcranial Magnetic Stimulation in Major Depressive Disorder and Posttraumatic Stress Disorder. J Pers Med 2022; 12:jpm12020224. [PMID: 35207712 PMCID: PMC8874724 DOI: 10.3390/jpm12020224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 01/07/2022] [Accepted: 01/27/2022] [Indexed: 01/09/2023] Open
Abstract
The diagnostic categories in psychiatry often encompass heterogeneous symptom profiles associated with differences in the underlying etiology, pathogenesis and prognosis. Prior work demonstrated that some of this heterogeneity can be quantified though dimensional analysis of the Depression Anxiety Stress Scale (DASS), yielding unique transdiagnostic symptom subtypes. This study investigated whether classifying patients according to these symptom profiles would have prognostic value for the treatment response to therapeutic transcranial magnetic stimulation (TMS) in comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). A linear discriminant model was constructed using a simulation dataset to classify 35 participants into one of the following six pre-defined symptom profiles: Normative Mood, Tension, Anxious Arousal, Generalized Anxiety, Anhedonia and Melancholia. Clinical outcomes with TMS across MDD and PTSD were assessed. All six symptom profiles were present. After TMS, participants with anxious arousal were less likely to achieve MDD remission compared to other subtypes (FET, odds ratio 0.16, p = 0.034), exhibited poorer PTSD symptom reduction (21% vs. 46%; t (33) = 2.025, p = 0.051) and were less likely to complete TMS (FET, odds ratio 0.066, p = 0.011). These results offer preliminary evidence that classifying individuals according to these transdiagnostic symptom profiles may offer a simple method to inform TMS treatment decisions.
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30
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Mirman AM, Corlier J, Wilson AC, Tadayonnejad R, Marder KG, Pleman CM, Krantz DE, Wilke SA, Levitt JG, Ginder ND, Ojha R, Daskalakis ZJ, Leuchter AF, Lee JC. Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder. Depress Anxiety 2022; 39:123-133. [PMID: 34990046 DOI: 10.1002/da.23237] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 10/06/2021] [Accepted: 12/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Symptoms of major depressive disorder (MDD) are reported to change early in treatment with repetitive transcranial magnetic stimulation (rTMS). We evaluated early changes in sleep, anxiety, and mood as predictors of nonresponse to rTMS treatment. METHODS Three hundred twenty-nine subjects with nonpsychotic MDD completed a 6-week course of rTMS treatment. Subjects were stratified by the severity of their baseline depression, and had their overall depressive symptoms recorded every week of treatment. We evaluated lack of improvement in sleep, anxiety, and mood symptoms after 1 and 2 weeks as potential predictors of eventual nonresponse, defined as <50% improvement in compositive depressive symptoms after 6 weeks. This was measured as negative predictive value (NPV; the likelihood that lack of early symptom improvement accurately predicted eventual treatment nonresponse). RESULTS Subjects with severe or very severe baseline depression achieving <20% improvement in mood at 1 week were correctly predicted as nonresponders with NPVs largely >90%. At 2 weeks, subjects with very severe baseline depression who failed to demonstrate any improvement in mood were all nonresponders. Lack of improvement in sleep at 2 weeks was also a significant predictor. CONCLUSIONS Identifying a lack of early mood improvement is a practical and robust method to predict rTMS nonresponse. This suggests a treatment protocol change may be indicated in patients with more severe baseline depression showing minimal early mood improvement.
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Affiliation(s)
- Alex M Mirman
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Juliana Corlier
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Andrew C Wilson
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Reza Tadayonnejad
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Division of the Humanities and Social Sciences, California Institute of Technology, Pasadena, California, USA
| | - Katharine G Marder
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Christopher M Pleman
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - David E Krantz
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Scott A Wilke
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Jennifer G Levitt
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Nathaniel D Ginder
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Rashi Ojha
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Zafiris J Daskalakis
- Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, California, USA
| | - Andrew F Leuchter
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Jonathan C Lee
- Neuromodulation Division, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, California, USA.,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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Muscat SA, Wright GD, Bergeron K, Morin KW, Crouch CR, Hartelius G. Ketamine-Assisted and Culturally Attuned Trauma Informed Psychotherapy as Adjunct to Traditional Indigenous Healing: Effecting Cultural Collaboration in Canadian Mental Health Care. Behav Sci (Basel) 2021; 11:118. [PMID: 34562957 PMCID: PMC8468330 DOI: 10.3390/bs11090118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/24/2021] [Accepted: 07/31/2021] [Indexed: 12/03/2022] Open
Abstract
Ketamine therapy with culturally attuned trauma-informed psychotherapy in a collaborative cross-cultural partnership may provide a critical step in the operationalization and optimization of treatment effectiveness in diverse populations and may provide a foundation for an improved quality of life for Indigenous people. Decolonizing Indigenous health and wellbeing is long overdue, requiring an equal partnership between government and Indigenous communities, built upon an aboriginal culture holistic foundation of balance of mind, body, social and spiritual realms, and within the context of historical and lived experiences of colonialism. Culturally attuned trauma-informed psychotherapy paired with ketamine-a fast-acting antidepressant that typically takes effect within 4 hours, even in cases of acute suicidality-may be uniquely qualified to integrate into an Indigenous based health system, since ketamine's therapeutic effects engage multiple neuropsychological, physiological, biological, and behavioral systems damaged by intergenerational complex developmental trauma. Ketamine holds the potential to serve as a core treatment modality around which culturally engaged treatment approaches might be organized since its brief alteration of normal waking consciousness is already a familiar and intrinsic element of healing culture in many Indigenous societies. There is great need and desire in Indigenous communities for respectful and sacred partnership in fostering more effective mental health outcomes and improved quality of life.
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Affiliation(s)
- Sherry-Anne Muscat
- Youth Forensic Psychiatry, Alberta Hospital, Alberta Health Services, 17480 Fort Road, Edmonton, AB T5J 2J7, Canada
- Integral and Transpersonal Psychology, California Institute of Integral Studies, San Francisco, CA 94103, USA; (C.R.C.); (G.H.)
| | - Geralyn Dorothy Wright
- CreeAtion Community Care Society, Enoch Cree Nation, Chief Lapotac Blvd NW Suite 102, Enoch, AB T7X 3Y3, Canada; (G.D.W.); (K.B.)
| | - Kristy Bergeron
- CreeAtion Community Care Society, Enoch Cree Nation, Chief Lapotac Blvd NW Suite 102, Enoch, AB T7X 3Y3, Canada; (G.D.W.); (K.B.)
| | - Kevin W. Morin
- Department of Psychiatry, University of Alberta, 116 St & 85 Ave, Edmonton, AB T6G 2R3, Canada;
- Acute Adult Psychiatry, Alberta Hospital, Alberta Health Services, 17480 Fort Road, Edmonton, AB T5J 2J7, Canada
| | - Courtenay Richards Crouch
- Integral and Transpersonal Psychology, California Institute of Integral Studies, San Francisco, CA 94103, USA; (C.R.C.); (G.H.)
| | - Glenn Hartelius
- Integral and Transpersonal Psychology, California Institute of Integral Studies, San Francisco, CA 94103, USA; (C.R.C.); (G.H.)
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Clinical effectiveness of non-TMS neurostimulation in depression: Clinical trials from 2010 to 2020. Prog Neuropsychopharmacol Biol Psychiatry 2021; 110:110287. [PMID: 33610609 DOI: 10.1016/j.pnpbp.2021.110287] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 02/10/2021] [Accepted: 02/12/2021] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Treatment for major depressive disorder (MDD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the non-transcranial magnetic stimulation (non-TMS) neurostimulation treatment for MDD. METHODS The authors reviewed non-TMS neurostimulation clinical trials for MDD between 2010 and 2020. Electroconvulsive therapy was not included in this review. A systematic review was performed in MEDLINE database through PubMed, the Cochrane Collaboration's Clinical Trials Register (CENTRAL), PsycINFO and Thomson Reuters's Web of Science. RESULTS Only 20 articles met the inclusion criteria. Randomized controlled trials demonstrated efficacy of transcranial direct current stimulation (tDCS) in five of seven trials. tDCS augmented with sertraline, fluoxetine, citalopram and escitalopram was superior to placebo and to tDCS only. A comparative trial demonstrated that the duration of tDCS sessions can modulate the effectiveness of this treatment. Open trials indicated that deep brain stimulation, epidural cortical stimulation, trigeminal nerve stimulation, magnetic seizure therapy and vagus nerve stimulation may be effective in treatment-resistant depression. CONCLUSION This review confirmed the efficacy of tDCS in MDD. Despite new evidence showing effectiveness for other non-TMS neurostimulation, their effectiveness is still unclear. Non-TMS neurostimulation RCTs with large samples and head-to-head studies comparing non-TMS neurostimulation and gold standard pharmacological treatments are still lacking.
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33
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Miuli A, Sepede G, Stigliano G, Mosca A, Di Carlo F, d’Andrea G, Lalli A, Spano MC, Pettorruso M, Martinotti G, di Giannantonio M. Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders: A systematic review and meta-analysis. World J Psychiatry 2021; 11:477-490. [PMID: 34513609 PMCID: PMC8394688 DOI: 10.5498/wjp.v11.i8.477] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/24/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs.
AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD.
METHODS We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code.
RESULTS Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions.
CONCLUSION Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.
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Affiliation(s)
- Andrea Miuli
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Gianna Sepede
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Gianfranco Stigliano
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Alessio Mosca
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Francesco Di Carlo
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Giacomo d’Andrea
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Aliseo Lalli
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Maria Chiara Spano
- Department of Psychiatry Affective Neuropsychiatry, Sahlgrenska University Hospital, Göteborg 40530, Sweden
| | - Mauro Pettorruso
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
| | - Giovanni Martinotti
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
- Department of Pharmacy, Clinical Science, University of Hertfordshire, Herts AL10 9AB, Italy
| | - Massimo di Giannantonio
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d'Annunzio” University of Chieti, Chieti 66100, Italy
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Sorkhabi MM, Benjaber M, Wendt K, West TO. Programmable Transcranial Magnetic Stimulation: A Modulation Approach for the Generation of Controllable Magnetic Stimuli. IEEE Trans Biomed Eng 2021; 68:1847-1858. [PMID: 32946379 PMCID: PMC7610606 DOI: 10.1109/tbme.2020.3024902] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
OBJECTIVE A transcranial magnetic stimulation system with programmable stimulus pulses and patterns is presented. The stimulus pulses of the implemented system expand beyond conventional damped cosine or near-rectangular pulses and approach an arbitrary waveform. METHODS The desired stimulus waveform shape is defined as a reference signal. This signal controls the semiconductor switches of an H-bridge inverter to generate a high-power imitation of the reference. The design uses a new paradigm for TMS, applying pulse-width modulation with a non-resonant, high-frequency switching architecture to synthesize waveforms that leverages the low-pass filtering properties of neuronal cells. The modulation technique enables control of the waveform, frequency, pattern, and intensity of the stimulus. RESULTS A system prototype was developed to demonstrate the technique. The experimental measurements demonstrate that the system is capable of generating stimuli up to 4 kHz with peak voltage and current values of ±1000 V and ±3600 A, respectively. The maximum transferred energy measured in the experimental validation was 100.4 Joules. To characterize repetitive TMS modalities, the efficiency of generating consecutive pulse triplets and quadruplets with interstimulus intervals of 1 ms was tested and verified. CONCLUSION The implemented TMS device can generate consecutive rectangular pulses with a predetermined time interval, widths and polarities, enables the synthesis of a wide range of magnetic stimuli. SIGNIFICANCE New waveforms promise functional advantages over the waveforms generated by current-generation TMS systems for clinical neuroscience research.
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Affiliation(s)
| | - Moaad Benjaber
- MRC Brain Network Dynamics Unit, University of Oxford, Oxford, OX1 3TH, UK
| | - Karen Wendt
- MRC Brain Network Dynamics Unit, University of Oxford, Oxford, OX1 3TH, UK
| | - Timothy O. West
- MRC Brain Network Dynamics Unit, University of Oxford, Oxford, OX1 3TH, UK
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Majumder P, Balan S, Gupta V, Wadhwa R, Perera TD. The Safety and Efficacy of Repetitive Transcranial Magnetic Stimulation in the Treatment of Major Depression Among Children and Adolescents: A Systematic Review. Cureus 2021; 13:e14564. [PMID: 34026380 PMCID: PMC8133761 DOI: 10.7759/cureus.14564] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2021] [Indexed: 12/29/2022] Open
Abstract
Major depression is a chronic debilitating condition affecting people of all ages and is rising over the past decade. Major depression among children and adolescents is often resistant to traditional treatments, thus necessitating the exploration of novel strategies. Repetitive transcranial magnetic stimulation (rTMS) is gaining increasing attention as a useful tool in treating various conditions and has received the US Food and Drug Administration (FDA) approval to treat depression and obsessive-compulsive disorder among adults. Favorable outcomes among adults generated interest in using it among children. Until recently, the existing literature lacked randomized sham-controlled trials on this topic among children and adolescents. The newest additions in the literature necessitated another in-depth look at the data to explore the safety and efficacy of rTMS in the context of depression among children and adolescents. We searched the Medline and Cochrane databases and included 18 articles for our systematic review. Our systematic review indicates level 1 evidence that rTMS is safe but failed to show its superiority to placebo as a stand-alone treatment for resistant depression among children and adolescents. However, there is level 2 evidence favoring add-on rTMS to treat major depression among children and adolescents. The study subjects appear to tolerate the rTMS treatment well with some minor and mostly self-limited side effects. Risks of treatment-emergent hypomanic symptoms and seizure appear to be very low. There is no evidence of worsening of suicidal ideation or cognitive decline during rTMS treatment.
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Affiliation(s)
| | | | - Vikas Gupta
- Psychiatry, South Carolina Department of Mental Health, Columbia, USA
| | - Roopma Wadhwa
- Psychiatry and Behavioral Sciences, South Carolina Department of Mental Health, South Carolina, USA
| | - Tarique D Perera
- Psychiatry and Behavioral Sciences, Contemporary Care, Greenwich, USA
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Miron JP, Voetterl H, Fox L, Hyde M, Mansouri F, Dees S, Zhou R, Sheen J, Desbeaumes Jodoin V, Mir-Moghtadaei A, Blumberger DM, Daskalakis ZJ, Vila-Rodriguez F, Downar J. Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study. Psychiatry Res 2021; 298:113790. [PMID: 33581379 DOI: 10.1016/j.psychres.2021.113790] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 02/03/2021] [Indexed: 01/29/2023]
Abstract
Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.
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Affiliation(s)
- Jean-Philippe Miron
- Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Centre de Recherche du CHUM (CRCHUM) et Département de Psychiatrie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada.
| | - Helena Voetterl
- Krembil Research Institute, University Health Network, Toronto, ON, Canada; Department of Cognitive Neuroscience, Maastricht University, Maastricht, Limburg, Netherland
| | - Linsay Fox
- Krembil Research Institute, University Health Network, Toronto, ON, Canada
| | - Molly Hyde
- Krembil Research Institute, University Health Network, Toronto, ON, Canada
| | - Farrokh Mansouri
- Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Sinjin Dees
- Faculty of Engineering, McMaster University, Hamilton, ON, Canada
| | - Ryan Zhou
- Krembil Research Institute, University Health Network, Toronto, ON, Canada
| | - Jack Sheen
- Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Véronique Desbeaumes Jodoin
- Centre Hospitalier de l'Université de Montréal (CHUM), Centre de Recherche du CHUM (CRCHUM) et Département de Psychiatrie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Arsalan Mir-Moghtadaei
- Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Daniel M Blumberger
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention at the Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Zafiris J Daskalakis
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention at the Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of California San Diego, San Diego, California, United States
| | - Fidel Vila-Rodriguez
- Non-Invasive Neurostimulation Therapies Laboratory, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Jonathan Downar
- Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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Guerrero Moreno J, Biazoli CE, Baptista AF, Trambaiolli LR. Closed-loop neurostimulation for affective symptoms and disorders: An overview. Biol Psychol 2021; 161:108081. [PMID: 33757806 DOI: 10.1016/j.biopsycho.2021.108081] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 12/28/2022]
Abstract
Affective and anxiety disorders are the most prevalent and incident psychiatric disorders worldwide. Therapeutic approaches to these disorders using non-invasive brain stimulation (NIBS) and analogous techniques have been extensively investigated. In this paper, we discuss the combination of NIBS and neurofeedback in closed-loop setups and its application for affective symptoms and disorders. For this, we first provide a rationale for this combination by presenting some of the main original findings of NIBS, with a primary focus on transcranial magnetic stimulation (TMS), and neurofeedback, including protocols based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Then, we provide a scope review of studies combining real-time neurofeedback with NIBS protocols in the so-called closed-loop brain state-dependent neuromodulation (BSDS). Finally, we discuss the concomitant use of TMS and real-time functional near-infrared spectroscopy (fNIRS) as a possible solution to the current limitations of BSDS-based protocols for affective and anxiety disorders.
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Affiliation(s)
- Javier Guerrero Moreno
- Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo André, Brazil
| | - Claudinei Eduardo Biazoli
- Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo André, Brazil; Department of Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, UK
| | - Abrahão Fontes Baptista
- Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo André, Brazil; Laboratory of Medical Investigations 54 (LIM-54), Universidade de São Paulo, São Paulo, Brazil; NAPeN Network (Rede de Núcleos de Assistência e Pesquisa em Neuromodulação), Brazil; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN/CEPID-FAPESP), University of Campinas, Campinas, São Paulo, Brazil
| | - Lucas Remoaldo Trambaiolli
- McLean Hospital, Harvard Medical School, Boston, USA; School of Medicine and Dentistry, University of Rochester, Rochester, USA.
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Cosmo C, Zandvakili A, Petrosino NJ, Berlow YA, Philip NS. Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: Recent Critical Advances in Patient Care. CURRENT TREATMENT OPTIONS IN PSYCHIATRY 2021; 8:47-63. [PMID: 33723500 PMCID: PMC7946620 DOI: 10.1007/s40501-021-00238-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 02/26/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE Transcranial magnetic stimulation (TMS) is an evidence-based treatment for pharmacoresistant major depressive disorder (MDD). In the last decade, the field has seen significant advances in the understanding and use of this new technology. This review aims to describe the large, randomized controlled studies leading to the modern use of rTMS for MDD. It also includes a special section briefly discussing the use of these technologies during the COVID-19 pandemic. RECENT FINDINGS Several new approaches and technologies are emerging in this field, including novel approaches to reduce treatment time and potentially yield new approaches to optimize and maximize clinical outcomes. Of these, theta burst TMS now has evidence indicating it is non-inferior to standard TMS and provides significant advantages in administration. Recent studies also indicate that neuroimaging and related approaches may be able to improve TMS targeting methods and potentially identify those patients most likely to respond to stimulation. SUMMARY While new data is promising, significant research remains to be done to individualize and optimize TMS procedures. Emerging new approaches, such as accelerated TMS and advanced targeting methods, require additional replication and demonstration of real-world clinical utility. Cautious administration of TMS during the pandemic is possible with careful attention to safety procedures.
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Affiliation(s)
- Camila Cosmo
- VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Healthcare System, 830 Chalkstone Ave, Providence, 02908 USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI USA
| | - Amin Zandvakili
- VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Healthcare System, 830 Chalkstone Ave, Providence, 02908 USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI USA
| | - Nicholas J. Petrosino
- VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Healthcare System, 830 Chalkstone Ave, Providence, 02908 USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI USA
| | - Yosef A. Berlow
- VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Healthcare System, 830 Chalkstone Ave, Providence, 02908 USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI USA
| | - Noah S. Philip
- VA RR&D Center for Neurorestoration and Neurotechnology, Providence VA Healthcare System, 830 Chalkstone Ave, Providence, 02908 USA
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI USA
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Lee HJ, Kim SM, Kwon JY. Repetitive transcranial magnetic stimulation treatment for peripartum depression: systematic review & meta-analysis. BMC Pregnancy Childbirth 2021; 21:118. [PMID: 33563220 PMCID: PMC7874443 DOI: 10.1186/s12884-021-03600-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/28/2021] [Indexed: 12/29/2022] Open
Abstract
Background Peripartum depression is a common disorder with very high potential hazards for both the patients and their babies. The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression. Methods We performed a systematic review that followed the PRISMA guidelines. We searched for studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference, and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method. Results The therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.944–1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.689–1.459), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346 (95% CI: 0.214–0.506), a meaningful result. There were no severe side effects to the mothers or fetuses. Conclusions From various perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-021-03600-3.
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Affiliation(s)
- Hyune June Lee
- Department of Medical Devices Industry, Dongguk University, Seoul, South Korea
| | - Sung Min Kim
- Department of Medical Devices Industry, Dongguk University, Seoul, South Korea
| | - Ji Yean Kwon
- Department of Medical Devices Industry, Dongguk University, Seoul, South Korea.
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Malhi GS, Bell E, Bassett D, Boyce P, Bryant R, Hazell P, Hopwood M, Lyndon B, Mulder R, Porter R, Singh AB, Murray G. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2021; 55:7-117. [PMID: 33353391 DOI: 10.1177/0004867420979353] [Citation(s) in RCA: 299] [Impact Index Per Article: 74.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES To provide advice and guidance regarding the management of mood disorders, derived from scientific evidence and supplemented by expert clinical consensus to formulate s that maximise clinical utility. METHODS Articles and information sourced from search engines including PubMed, EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (e.g. books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Relevant information was appraised and discussed in detail by members of the mood disorders committee, with a view to formulating and developing consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous consultation and external review involving: expert and clinical advisors, key stakeholders, professional bodies and specialist groups with interest in mood disorders. RESULTS The Royal Australian and New Zealand College of Psychiatrists mood disorders clinical practice guidelines 2020 (MDcpg2020) provide up-to-date guidance regarding the management of mood disorders that is informed by evidence and clinical experience. The guideline is intended for clinical use by psychiatrists, psychologists, primary care physicians and others with an interest in mental health care. CONCLUSION The MDcpg2020 builds on the previous 2015 guidelines and maintains its joint focus on both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. MOOD DISORDERS COMMITTEE Gin S Malhi (Chair), Erica Bell, Darryl Bassett, Philip Boyce, Richard Bryant, Philip Hazell, Malcolm Hopwood, Bill Lyndon, Roger Mulder, Richard Porter, Ajeet B Singh and Greg Murray.
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Affiliation(s)
- Gin S Malhi
- The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, NSW, Australia.,Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.,CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
| | - Erica Bell
- The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, NSW, Australia.,Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.,CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia
| | | | - Philip Boyce
- Department of Psychiatry, Westmead Hospital and the Westmead Clinical School, Wentworthville, NSW, Australia.,Discipline of Psychiatry, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Richard Bryant
- School of Psychology, University of New South Wales, Sydney, NSW, Australia
| | - Philip Hazell
- Discipline of Psychiatry, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Malcolm Hopwood
- Department of Psychiatry, University of Melbourne and Professorial Psychiatry Unit, Albert Road Clinic, Melbourne, VIC, Australia
| | - Bill Lyndon
- The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, NSW, Australia
| | - Roger Mulder
- Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
| | - Richard Porter
- Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
| | - Ajeet B Singh
- The Geelong Clinic Healthscope, IMPACT - Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC, Australia
| | - Greg Murray
- Centre for Mental Health, Swinburne University of Technology, Hawthorn, VIC, Australia
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Strategies for augmentation of high-frequency left-sided repetitive transcranial magnetic stimulation treatment of major depressive disorder. J Affect Disord 2020; 277:964-969. [PMID: 33065840 DOI: 10.1016/j.jad.2020.09.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/24/2020] [Accepted: 09/02/2020] [Indexed: 01/29/2023]
Abstract
BACKGROUND Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective intervention for treatment-resistant Major Depressive Disorder (MDD). Early improvement during high-frequency left-sided (HFL) stimulation of the dorsolateral prefrontal cortex (DLPFC) is an important predictor of longer-term outcome, but most patients benefit later in their treatment course. We examined patients without early improvement with HFL to determine whether augmentation with additional stimulation approaches improved treatment outcome. METHODS 139 participants received HFL in a measurement-based care paradigm. Participants who achieved < 20% improvement by treatment 10 could continue with HFL (N = 17) or receive one of two augmentation strategies: bilateral stimulation (BL; HFL followed by low-frequency stimulation of right DLPFC) (N = 69) or intermittent theta-burst priming of left DLPFC (iTBS-P) (N = 17) for their remaining treatment sessions. The primary outcome was the percent reduction in depressive symptoms at treatment 30. RESULTS Participants who achieved < 20% improvement by treatment 10 and continued with HFL showed limited benefit. iTBS-P participants had significantly greater improvement, while those receiving BL trended toward improved outcomes. Ten sessions of either augmentation strategy appeared necessary to determine the likelihood of benefit. CONCLUSIONS Augmentation of early non-response to HFL appears to improve rTMS outcomes, with a novel iTBS-P strategy surpassing both continued HFL or BL treatment in participants with < 20% improvement after 10 treatments. These findings suggest that measurement-based care with addition of augmented stimulation for those not showing early improvement may yield superior rTMS treatment outcomes.
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Baeken C, Wu G, Sackeim HA. Accelerated iTBS treatment applied to the left DLPFC in depressed patients results in a rapid volume increase in the left hippocampal dentate gyrus, not driven by brain perfusion. Brain Stimul 2020; 13:1211-1217. [DOI: 10.1016/j.brs.2020.05.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 05/15/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
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Bickman L. Improving Mental Health Services: A 50-Year Journey from Randomized Experiments to Artificial Intelligence and Precision Mental Health. ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH 2020; 47:795-843. [PMID: 32715427 PMCID: PMC7382706 DOI: 10.1007/s10488-020-01065-8] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This conceptual paper describes the current state of mental health services, identifies critical problems, and suggests how to solve them. I focus on the potential contributions of artificial intelligence and precision mental health to improving mental health services. Toward that end, I draw upon my own research, which has changed over the last half century, to highlight the need to transform the way we conduct mental health services research. I identify exemplars from the emerging literature on artificial intelligence and precision approaches to treatment in which there is an attempt to personalize or fit the treatment to the client in order to produce more effective interventions.
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Affiliation(s)
- Leonard Bickman
- Center for Children and Families; Psychology, Academic Health Center 1, Florida International University, 11200 Southwest 8th Street, Room 140, Miami, FL, 33199, USA.
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Repetitive transcranial magnetic stimulation as an alternative therapy for stroke with spasticity: a systematic review and meta-analysis. J Neurol 2020; 268:4013-4022. [PMID: 32654060 DOI: 10.1007/s00415-020-10058-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 07/03/2020] [Accepted: 07/04/2020] [Indexed: 10/23/2022]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) can be used to manage post-stroke spasticity, but a meta-analysis of the recent randomized-controlled trials (RCTs) is lacking. Our aim is to perform a meta-analysis of the RCTs that investigated the efficacy of rTMS in patients with post-stroke spasticity. PubMed, Embase, and Cochrane Library databases were searched for eligible papers published up to February 2020. The primary outcome was the Modified Ashworth Scale (MAS), measured as the effect of rTMS compared with controls and after rTMS (using a change score calculated separately in the active and sham treatment groups). Finally, five papers and eight data sets were included. rTMS had no significant benefit on MAS in patients with post-stroke spasticity compared to sham treatment (WMD = - 0.29, 95% CI - 0.58, 0.00; P = 0.051). When analyzing the change score in the treatment groups, a significant effect of rTMS was observed (WMD = - 0.27, 95% CI - 0.51, - 0.04; P = 0.024). When analyzing the change score in the sham treatment groups, no significant effect of sham treatment was observed, indicating no placebo effect (WMD = 0.32, 95% CI: - 0.40, 1.04; P = 0.387). We included the sample size, year of publication, percentage of male patients, and age difference in each study as covariates, and performed a meta-regression. The results showed no association between these variables and the MAS. Compared with sham stimulation, rTMS did not show a significant reduction in MAS for the patients who experienced post-stroke spasticity, but the patients reported a better outcome in MAS on a before-after scenario.
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Corticostriatal functional connectivity of bothersome tinnitus in single-sided deafness. Sci Rep 2019; 9:19552. [PMID: 31863033 PMCID: PMC6925178 DOI: 10.1038/s41598-019-56127-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 12/06/2019] [Indexed: 02/06/2023] Open
Abstract
Subjective tinnitus is an auditory phantom perceptual disorder without an objective biomarker. Bothersome tinnitus in single-sided deafness (SSD) is particularly challenging to treat because the deaf ear can no longer be stimulated by acoustic means. We contrasted an SSD cohort with bothersome tinnitus (TIN; N = 15) against an SSD cohort with no or non-bothersome tinnitus (NO TIN; N = 15) using resting-state functional magnetic resonance imaging (fMRI). All study participants had normal hearing in one ear and severe or profound hearing loss in the other. We evaluated corticostriatal functional connectivity differences by placing seeds in the caudate nucleus and Heschl’s Gyrus (HG) of both hemispheres. The TIN cohort showed increased functional connectivity between the left caudate and left HG, and left and right HG and the left caudate. Within the TIN cohort, functional connectivity between the right caudate and cuneus was correlated with the Tinnitus Functional Index (TFI) relaxation subscale. And, functional connectivity between the right caudate and superior lateral occipital cortex, and the right caudate and anterior supramarginal gyrus were correlated with the TFI control subscale. These findings support a striatal gating model of tinnitus and suggest tinnitus biomarkers to monitor treatment response and to target specific brain areas for innovative neuromodulation therapies.
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