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Neufeld NH, Blumberger DM. An Update on the Use of Neuromodulation Strategies in the Treatment of Schizophrenia. Am J Psychiatry 2025; 182:332-340. [PMID: 40165555 DOI: 10.1176/appi.ajp.20250068] [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] [Indexed: 04/02/2025]
Abstract
The field of neuromodulation has evolved tremendously and now includes a vast array of interventions utilizing different technologies that span electrical, magnetic, and ultrasound forms of stimulation. The evolution of interventions holds the promise of fewer adverse effects and a noninvasive approach, increasing the scale at which these interventions may be offered in hospital and community settings. While the majority of neuromodulation studies have focused on patients with mood disorders, predominantly depression, there is an unmet need for patients with schizophrenia, who are in dire need of novel therapeutic options. Advances in neuroimaging and approaches for examining individual variability and transdiagnostic symptoms may lead to more effective neuromodulation treatments in this patient population. This overview explores the modern landscape of invasive and noninvasive neuromodulation treatments for patients with schizophrenia. It begins with approaches that involve diffuse stimulation of the cortex and subcortex and then reviews more focal stimulation approaches at the cortical and subcortical levels. The authors also reflect on the relationship between our understanding of the neurobiology of schizophrenia and neuromodulation interventions.
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Affiliation(s)
- Nicholas H Neufeld
- Kimel Family Translational Imaging-Genetics Laboratory (Neufeld), Campbell Family Mental Health Research Institute (Neufeld, Blumberger), Schizophrenia Division (Neufeld), and Temerty Centre for Therapeutic Brain Intervention (Neufeld, Blumberger), Centre for Addiction and Mental Health (CAMH), Toronto; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto (Neufeld, Blumberger)
| | - Daniel M Blumberger
- Kimel Family Translational Imaging-Genetics Laboratory (Neufeld), Campbell Family Mental Health Research Institute (Neufeld, Blumberger), Schizophrenia Division (Neufeld), and Temerty Centre for Therapeutic Brain Intervention (Neufeld, Blumberger), Centre for Addiction and Mental Health (CAMH), Toronto; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto (Neufeld, Blumberger)
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Blyth SH, Cruz Bosch C, Raffoul JJ, Chesley J, Johnson B, Borodge D, Sagarwala R, Masters R, Brady RO, Vandekar S, Ward HB. Safety of rTMS for Schizophrenia: A Systematic Review and Meta-analysis. Schizophr Bull 2025; 51:392-400. [PMID: 39278637 PMCID: PMC11908856 DOI: 10.1093/schbul/sbae158] [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] [Indexed: 09/18/2024]
Abstract
BACKGROUND AND HYPOTHESIS Current treatments for schizophrenia are only partially effective, and there are no medications for negative symptoms or cognitive impairment. Neuromodulation, such as repetitive transcranial magnetic stimulation (rTMS), has potential as a novel intervention for schizophrenia. Prior to clinical use, rTMS should have demonstrated safety in a large schizophrenia population. However, the safety profile of rTMS in schizophrenia is not well characterized, and regulatory agencies have expressed concern about safety in this population. STUDY DESIGN We conducted a systematic review with meta-analysis of rTMS studies in schizophrenia. We searched PubMed, the Cochrane Library, PsycINFO, and Science Citation Index Expanded for rTMS studies in schizophrenia that reported adverse effects. We extracted the number of participants who experienced an adverse effect and calculated the prevalence of each adverse effect for active or sham rTMS. We tested the difference between the prevalence of events in the active and sham conditions. We assessed risk of bias using the Cochrane Handbook. STUDY RESULTS The initial search identified 1472 studies. After screening, 261 full-text studies were assessed, and 126 met inclusion criteria (N = 4122 total subjects). The prevalence of headache or scalp pain, dizziness or syncope, facial twitching, and nausea was higher for active rTMS compared to sham (P < .05). The prevalence of all other adverse effects, including seizure, was not different between active and sham rTMS. CONCLUSIONS rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure, compared to the general population.
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Affiliation(s)
- Sophia H Blyth
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Claudia Cruz Bosch
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Julian J Raffoul
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jordyn Chesley
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Benjamin Johnson
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Darara Borodge
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Raza Sagarwala
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Ross Masters
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Roscoe O Brady
- Department of Psychiatry, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
- McLean Hospital, Belmont, MA, USA
| | - Simon Vandekar
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Heather Burrell Ward
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA
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3
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Lian X, Song W, Si TM, Lian NZ. Classification of musical hallucinations and the characters along with neural-molecular mechanisms of musical hallucinations associated with psychiatric disorders. World J Psychiatry 2024; 14:1386-1396. [PMID: 39319238 PMCID: PMC11417650 DOI: 10.5498/wjp.v14.i9.1386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 08/15/2024] [Accepted: 08/22/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Musical hallucinations (MH) involve the false perception of music in the absence of external stimuli which links with different etiologies. The pathomechanisms of MH encompass various conditions. The etiological classification of MH is of particular importance and offers valuable insights to understand MH, and further to develop the effective treatment of MH. Over the recent decades, more MH cases have been reported, revealing newly identified medical and psychiatric causes of MH. Functional imaging studies reveal that MH activates a wide array of brain regions. An up-to-date analysis on MH, especially on MH comorbid psychiatric conditions is warranted. AIM To propose a new classification of MH; to study the age and gender differences of MH in mental disorders; and neuropathology of MH. METHODS Literatures searches were conducted using keywords such as "music hallucination," "music hallucination and mental illness," "music hallucination and gender difference," and "music hallucination and psychiatric disease" in the databases of PubMed, Google Scholar, and Web of Science. MH cases were collected and categorized based on their etiologies. The t-test and ANOVA were employed (P < 0.05) to compare the age differences of MH different etiological groups. Function neuroimaging studies of neural networks regulating MH and their possible molecular mechanisms were discussed. RESULTS Among the 357 yielded publications, 294 MH cases were collected. The average age of MH cases was 67.9 years, with a predominance of females (66.8% females vs 33.2% males). MH was classified into eight groups based on their etiological mechanisms. Statistical analysis of MH cases indicates varying associations with psychiatric diagnoses. CONCLUSION We carried out a more comprehensive review of MH studies. For the first time according to our knowledge, we demonstrated the psychiatric conditions linked and/or associated with MH from statistical, biological and molecular point of view.
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Affiliation(s)
- Xin Lian
- Department of Radiology and Biomedical Imaging, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan 030032, Shanxi Province, China
| | - Wei Song
- Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton L8S 4L8, ON, Canada
| | - Tian-Mei Si
- Department of Psychopharmacology, Peking University Sixth Hospital, Beijing 100191, China
| | - Naomi Zheng Lian
- Department of Psychiatry, Hartford HealthCare, St Vincent’s Medical Center, Westport, CT 06088, United States
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Fitzsimmons SMDD, Oostra E, Postma TS, van der Werf YD, van den Heuvel OA. Repetitive Transcranial Magnetic Stimulation-Induced Neuroplasticity and the Treatment of Psychiatric Disorders: State of the Evidence and Future Opportunities. Biol Psychiatry 2024; 95:592-600. [PMID: 38040046 DOI: 10.1016/j.biopsych.2023.11.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 11/16/2023] [Accepted: 11/18/2023] [Indexed: 12/03/2023]
Abstract
Neuroplasticity, or activity-dependent neuronal change, is a crucial mechanism underlying the mechanisms of effect of many therapies for neuropsychiatric disorders, one of which is repetitive transcranial magnetic stimulation (rTMS). Understanding the neuroplastic effects of rTMS at different biological scales and on different timescales and how the effects at different scales interact with each other can help us understand the effects of rTMS in clinical populations and offers the potential to improve treatment outcomes. Several decades of research in the fields of neuroimaging and blood biomarkers is increasingly showing its clinical relevance, allowing measurement of the synaptic, functional, and structural changes involved in neuroplasticity in humans. In this narrative review, we describe the evidence for rTMS-induced neuroplasticity at multiple levels of the nervous system, with a focus on the treatment of psychiatric disorders. We also describe the relationship between neuroplasticity and clinical effects, discuss methods to optimize neuroplasticity, and identify future research opportunities in this area.
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Affiliation(s)
- Sophie M D D Fitzsimmons
- Department of Psychiatry, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention Program, Amsterdam, the Netherlands.
| | - Eva Oostra
- Department of Psychiatry, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, the Netherlands; GGZ inGeest Mental Health Care, Amsterdam, the Netherlands
| | - Tjardo S Postma
- Department of Psychiatry, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention Program, Amsterdam, the Netherlands; GGZ inGeest Mental Health Care, Amsterdam, the Netherlands
| | - Ysbrand D van der Werf
- Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention Program, Amsterdam, the Netherlands
| | - Odile A van den Heuvel
- Department of Psychiatry, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Anatomy and Neurosciences, Amsterdam University Medical Centers, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention Program, Amsterdam, the Netherlands
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Roalf DR, Figee M, Oathes DJ. Elevating the field for applying neuroimaging to individual patients in psychiatry. Transl Psychiatry 2024; 14:87. [PMID: 38341414 PMCID: PMC10858949 DOI: 10.1038/s41398-024-02781-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 12/06/2023] [Accepted: 01/15/2024] [Indexed: 02/12/2024] Open
Abstract
Although neuroimaging has been widely applied in psychiatry, much of the exuberance in decades past has been tempered by failed replications and a lack of definitive evidence to support the utility of imaging to inform clinical decisions. There are multiple promising ways forward to demonstrate the relevance of neuroimaging for psychiatry at the individual patient level. Ultra-high field magnetic resonance imaging is developing as a sensitive measure of neurometabolic processes of particular relevance that holds promise as a new way to characterize patient abnormalities as well as variability in response to treatment. Neuroimaging may also be particularly suited to the science of brain stimulation interventions in psychiatry given that imaging can both inform brain targeting as well as measure changes in brain circuit communication as a function of how effectively interventions improve symptoms. We argue that a greater focus on individual patient imaging data will pave the way to stronger relevance to clinical care in psychiatry. We also stress the importance of using imaging in symptom-relevant experimental manipulations and how relevance will be best demonstrated by pairing imaging with differential treatment prediction and outcome measurement. The priorities for using brain imaging to inform psychiatry may be shifting, which compels the field to solidify clinical relevance for individual patients over exploratory associations and biomarkers that ultimately fail to replicate.
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Affiliation(s)
- David R Roalf
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Neurodevelopment & Psychosis Section, University of Pennsylvania, Philadelphia, PA, USA
| | - Martijn Figee
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Desmond J Oathes
- Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Center for Brain Imaging and Stimulation, University of Pennsylvania, Philadelphia, PA, USA.
- Center for Neuromodulation in Depression and Stress, University of Pennsylvania, Philadelphia, PA, USA.
- Penn Brain Science Translation, Innovation, and Modulation Center, University of Pennsylvania, Philadelphia, PA, USA.
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Brunelin J, Galvao F, Mondino M. Twice daily low frequency rTMS for treatment-resistant auditory hallucinations. Int J Clin Health Psychol 2023; 23:100344. [PMID: 36299491 PMCID: PMC9577245 DOI: 10.1016/j.ijchp.2022.100344] [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: 07/21/2022] [Accepted: 09/29/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) has emerged as a therapeutic solution in patients with treatment-resistant auditory verbal hallucinations. However, the optimal stimulation parameters remain unclear, especially for patients with clozapine-resistant symptoms. METHOD In an open label retrospective study, we investigated whether parameters of stimulation that were useful in patients with major depressive disorder would help schizophrenia patients with treatment-resistant auditory verbal hallucinations. Fourteen participants, including 9 under clozapine, received 30 sessions of 1 Hz rTMS over 3 weeks (360 pulses per sessions delivered with 60 s 'on' and 30 s 'off' at 110% of the resting motor threshold, 2 sessions per day). Stimulations were applied over the left temporoparietal junction (T3-P3 according to 10/20 system). RESULTS After rTMS, a significant decrease of auditory verbal hallucinations was observed (-38.7% ± 31.8, p = 0.003) on the Auditory Hallucination Rating Scale. The beneficial effects were also significant in the 9 patients who were also receiving clozapine (-34.9% ± 28.4, p = 0.01). CONCLUSIONS Low frequency rTMS, 30 sessions over 3 weeks, appears to be a suitable approach to decrease treatment-resistant auditory verbal hallucinations, including in patients with clozapine-resistant symptoms. Results from the current retrospective study in the clinical settings need to be confirmed by large-scale randomized sham-controlled trials.
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Affiliation(s)
- Jérôme Brunelin
- Pôle Est, Centre Hospitalier Le Vinatier, F69500 Bron, France,PSYR2 Team, Lyon Neuroscience Research Center, INSERM, U1028, CNRS, UMR5292, F-69000 Lyon, France,Université Lyon 1, Lyon University, F-69100 Villeurbanne, France,Corresponding author at: CH le Vinatier, PSYR2 team, bat 416 – 1st floor, 95 boulevard Pinel, 69678, BRON Cedex BP 30039, France.
| | - Filipe Galvao
- Pôle Est, Centre Hospitalier Le Vinatier, F69500 Bron, France,PSYR2 Team, Lyon Neuroscience Research Center, INSERM, U1028, CNRS, UMR5292, F-69000 Lyon, France,Université Lyon 1, Lyon University, F-69100 Villeurbanne, France
| | - Marine Mondino
- Pôle Est, Centre Hospitalier Le Vinatier, F69500 Bron, France,PSYR2 Team, Lyon Neuroscience Research Center, INSERM, U1028, CNRS, UMR5292, F-69000 Lyon, France,Université Lyon 1, Lyon University, F-69100 Villeurbanne, France
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7
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Shao Y, Yang Y, Sun YX, Xu AH. Different frequencies of repetitive transcranial magnetic stimulation combined with local injection of botulinum toxin type A for post-stroke lower limb spasticity: study protocol for a prospective, single-center, non-randomized, controlled clinical trial. Neural Regen Res 2022; 17:2491-2496. [PMID: 35535901 PMCID: PMC9120707 DOI: 10.4103/1673-5374.339011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
No definite consensus has currently been reached regarding the safety and efficacy of low- or high-frequency repetitive transcranial magnetic stimulation in the treatment of post-stroke muscle spasticity. The latest research indicates that when combined with local injections of botulinum toxin type A, it is more effective on post-stroke muscle spasticity than local injections of botulinum toxin type A alone. We designed a prospective, single-center, non-randomized, controlled clinical trial to investigate the safety and efficacy of different frequencies of repetitive transcranial magnetic stimulation combined with local injections of botulinum toxin type A in treating post-stroke lower limb muscle spasticity to determine an optimal therapeutic regimen. This trial will enroll 150 patients with post-stroke muscle spasticity admitted to the Department of Rehabilitation Medicine at the First Affiliated Hospital of China Medical University. All enrolled patients will undergo routine rehabilitation training and will be divided into five groups (n = 30 per group) according to the particular area of cerebral infarction and treatment methods. Group A: Patients with massive cerebral infarction will be given local injections of botulinum toxin type A and low-frequency (1 Hz) repetitive transcranial magnetic stimulation on the contralateral side; Group B: Patients with non-massive cerebral infarction will be given local injections of botulinum toxin type A and high-frequency (10–20 Hz) repetitive transcranial magnetic stimulation on the affected side; Group C: Patients with massive/non-massive cerebral infarction will be given local injections of botulinum toxin type A; Group D: Patients with massive cerebral infarction will be given low-frequency (1 Hz) repetitive transcranial magnetic stimulation on the contralateral side; and Group E: Patients with non-massive cerebral infarction will be given high-frequency (10–20 Hz) repetitive transcranial magnetic stimulation on the affected side. The primary outcome measure of this trial is a modified Ashworth scale score from 1 day before treatment to 12 months after treatment. Secondary outcome measures include Fugl-Meyer Assessment of Lower Extremity, Visual Analogue Scale, modified Barthel index, and Berg Balance Scale scores for the same time as specified for primary outcome measures. The safety indicator is the incidence of adverse events at 3–12 months after treatment. We hope to draw a definite conclusion on whether there are differences in the safety and efficacy of low- or high-frequency repetitive transcranial magnetic stimulation combined with botulinum toxin type A injections in the treatment of patients with post-stroke lower limb spasticity under strict grouping and standardized operation, thereby screening out the optimal therapeutic regimen. The study protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of China Medical University (approval No. [2021] 2021-333-3) on August 19, 2021. The trial was registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2100052180) on October 21, 2021. The protocol version is 1.1.
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Affiliation(s)
- Yang Shao
- Department of Rehabilitation Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yang Yang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yong-Xin Sun
- Department of Rehabilitation Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Ai-Hua Xu
- Department of Rehabilitation Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
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Hyde J, Carr H, Kelley N, Seneviratne R, Reed C, Parlatini V, Garner M, Solmi M, Rosson S, Cortese S, Brandt V. Efficacy of neurostimulation across mental disorders: systematic review and meta-analysis of 208 randomized controlled trials. Mol Psychiatry 2022; 27:2709-2719. [PMID: 35365806 PMCID: PMC8973679 DOI: 10.1038/s41380-022-01524-8] [Citation(s) in RCA: 119] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 02/28/2022] [Accepted: 03/10/2022] [Indexed: 01/29/2023]
Abstract
Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = -1.8 (95% CI: -2.6 to -1), and tDCS for symptoms of substance use disorder (-0.73, -1.00 to -0.46). There was also significant effects for TMS in obsessive-compulsive disorder (-0.66, -0.91 to -0.41) and unipolar depression symptoms (-0.60, -0.78 to -0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (-0.3, -0.55 to -0.05) and working memory (-0.38, -0.74 to -0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.
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Affiliation(s)
- Joshua Hyde
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK.
| | - Hannah Carr
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
| | - Nicholas Kelley
- Centre for Research on Self and Identity, School of Psychology, University of Southampton, Southampton, UK
| | - Rose Seneviratne
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
| | - Claire Reed
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
| | - Valeria Parlatini
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Matthew Garner
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
- Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK
| | - Marco Solmi
- Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada
- Department of Mental Health, The Ottawa Hospital, Ottawa, ON, Canada
| | - Stella Rosson
- Department of Mental Health, Azienda AULSS 3 Serenissima, Venice, Italy
| | - Samuele Cortese
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
- Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK
- Solent NHS Trust, Southampton, UK
- Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK
- Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA
| | - Valerie Brandt
- Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK
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Kronick J, Sabesan P, Burhan AM, Palaniyappan L. Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia. Schizophr Res 2022; 243:349-360. [PMID: 34183208 DOI: 10.1016/j.schres.2021.06.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 06/13/2021] [Accepted: 06/18/2021] [Indexed: 01/17/2023]
Abstract
Novel treatment modalities, such as non-invasive brain stimulation (NIBS), typically focus on patient groups that have failed multiple treatment interventions. Despite its promise, the clinical translation of NIBS in schizophrenia has been limited. One important obstacle to implementation is the inconsistent reporting of treatment resistance in the clinical trial literature contributing to heterogeneity in reported effects. In response, we develop a numerical approach to synthesize quality of assessment of Treatment-Resistant Schizophrenia (TRS) and apply this to studies investigating therapeutic response to NIBS in patients with schizophrenia. Literature search conducted through PubMed database identified 119 studies investigating Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in treating resistant schizophrenia symptoms. A quality score out of 11 was assigned to each study based on adherence to the international consensus guidelines for TRS developed by the Treatment Response and Resistance in Psychosis (TRRIP) group. Results revealed an overall paucity of studies with thorough assessment and/or reporting of TRS phenomenon, as evidenced by a mean quality score of 3.38/11 (SD: 1.01) for trials and 5.16/11 (SD: 1.57) for case reports, though this improved minimally since the publication of consensus criteria. Most studies considered treatment-resistance as a single dimensional construct by reporting resistance of a single symptom, and failed to establish treatment adherence, resistance time course and functional impairment. We conclude that the current NIBS literature in schizophrenia do not reflect its true effects on treatment-resistance. There is an urgent need to improve assessment and reporting standards of clinical trials that target TRS.
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Affiliation(s)
- Jami Kronick
- Schulich School of Medicine & Dentistry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5C1, Canada.
| | - Priyadharshini Sabesan
- Department of Psychiatry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7, Canada.
| | - Amer M Burhan
- Department of Psychiatry, University of Toronto, 250 College Street 8th floor, Toronto, Ontario M5T 1R8, Canada; Ontario Shores Centre for Mental Health Sciences, 700 Gordon Street, Whitby, Ontario L1N 5S9, Canada; Department of Psychiatry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7, Canada.
| | - Lena Palaniyappan
- Department of Psychiatry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7, Canada; Robarts Research Institute, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada; Lawson Health Research Institute, 750 Base Line Road East Suite 300, London, Ontario N6C 2R5, Canada.
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10
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Lorentzen R, Nguyen TD, McGirr A, Hieronymus F, Østergaard SD. The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: a systematic review and meta-analysis. SCHIZOPHRENIA (HEIDELBERG, GERMANY) 2022; 8:35. [PMID: 35853882 PMCID: PMC9261093 DOI: 10.1038/s41537-022-00248-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 03/21/2022] [Indexed: 04/20/2023]
Abstract
Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen's d) with 95% confidence intervals (95%CI) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.
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Affiliation(s)
- Rasmus Lorentzen
- Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Tuan D Nguyen
- Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Alexander McGirr
- Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Canada
- Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, Canada
| | - Fredrik Hieronymus
- Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Søren D Østergaard
- Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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11
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Ning Y, Zheng S, Feng S, Zhang B, Jia H. Potential Locations for Non-Invasive Brain Stimulation in Treating Schizophrenia: A Resting-State Functional Connectivity Analysis. Front Neurol 2022; 12:766736. [PMID: 34975725 PMCID: PMC8715096 DOI: 10.3389/fneur.2021.766736] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 11/09/2021] [Indexed: 11/25/2022] Open
Abstract
Introduction: Non-invasive brain stimulation (NIBS) techniques have been widely used for the purpose of improving clinical symptoms of schizophrenia. However, the ambiguous stimulation targets may limit the efficacy of NIBS for schizophrenia. Exploring effective stimulation targets may improve the clinical efficacy of NIBS in schizophrenia. Methods: We first conducted a neurosynth-based meta-analysis of 715 functional magnetic resonance imaging studies to identify schizophrenia-related brain regions as regions of interest. Then, we performed the resting-state functional connectivity analysis in 32 patients with first-episode schizophrenia to find brain surface regions correlated with the regions of interest in three pipelines. Finally, the 10–20 system coordinates corresponding to the brain surface regions were considered as potential targets for NIBS. Results: We identified several potential targets of NIBS, including the bilateral dorsal lateral prefrontal cortex, supplementary motor area, bilateral inferior parietal lobule, temporal pole, medial prefrontal cortex, precuneus, superior and middle temporal gyrus, and superior and middle occipital gyrus. Notably, the 10-20 system location of the bilateral dorsal lateral prefrontal cortex was posterior to F3 (F4), not F3 (F4). Conclusion: Conclusively, our findings suggested that the stimulation locations corresponding to these potential targets might help clinicians optimize the application of NIBS therapy in individuals with schizophrenia.
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Affiliation(s)
- Yanzhe Ning
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Sisi Zheng
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Sitong Feng
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Binlong Zhang
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongxiao Jia
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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12
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Guttesen LL, Albert N, Nordentoft M, Hjorthøj C. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation for auditory hallucinations in schizophrenia: Systematic review and meta-analysis. J Psychiatr Res 2021; 143:163-175. [PMID: 34500345 DOI: 10.1016/j.jpsychires.2021.09.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/25/2021] [Accepted: 09/01/2021] [Indexed: 11/16/2022]
Abstract
Through imaging studies, a significant increase in cerebral activity has been detected in fronto-temporal areas in patients experiencing auditory verbal hallucinations. Therefore, non-invasive neuromodulation, in particular transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), has been considered as a therapeutic intervention for medication-resistant auditory verbal hallucinations in schizophrenia. We aimed to synthesize results from randomized trials on either rTMS or tDCS versus placebo in patients with schizophrenia by including five recently published trials in the field. A systematic review and meta-analysis of relevant literature was conducted. Studies were included on the basis of pre-defined selection criteria. The quality of the studies was assessed by the Cochrane Risk of Bias Tool for Randomized Controlled Trials. RevMan 5.3 was used to conduct the statistical analysis. Including 465 and 960 patients, respectively, 12 tDCS and 27 rTMS studies were included. Regarding treatment of medication refractory auditory verbal hallucinations, no significant effect of tDCS (-0.23 [-0.49, 0.02], p = 0.08) or rTMS (-0.19 [-0.50, 0,11], p = 0.21) was found compared to sham in this meta-analysis. The current study found that it cannot be concluded that rTMS and tDCS are efficacious in treating medication-resistant auditory verbal hallucinations. Larger randomized controlled tDCS trials of a higher quality should be conducted in the future to establish substantial evidence of tDCS. The interventions appear safe and may have beneficial effects on other outcomes.
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Affiliation(s)
- Liv Liebach Guttesen
- Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Denmark; Psychiatric Center of Ballerup, Copenhagen University Hospital, Denmark
| | - Nikolai Albert
- Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Denmark; Psychiatry Region Zealand East, Roskilde, Denmark
| | - Merete Nordentoft
- Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Denmark
| | - Carsten Hjorthøj
- Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Denmark; University of Copenhagen, Department of Public Health, Section of Epidemiology, Denmark.
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13
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Marzouk T, Winkelbeiner S, Azizi H, Malhotra AK, Homan P. Transcranial Magnetic Stimulation for Positive Symptoms in Schizophrenia: A Systematic Review. Neuropsychobiology 2021; 79:384-396. [PMID: 31505508 DOI: 10.1159/000502148] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 07/16/2019] [Indexed: 11/19/2022]
Abstract
Transcranial magnetic stimulation (TMS) has been proposed as a potential treatment add-on for positive symptoms in schizophrenia. To summarize the current evidence for its efficacy, we reviewed clinical trials from the last 20 years that investigated TMS for positive symptoms. We performed a search on the PubMed database for clinical trials that used TMS for the treatment of positive symptoms published in peer-reviewed journals. We excluded reviews, case reports, and opinion papers. Of the 30 studies included, the majority (n = 25) investigated auditory verbal hallucinations. Twelve studies found evidence for a positive treatment effect of TMS on positive symptoms, while 18 did not find enough evidence to conclude that TMS is effective for positive symptoms. However, the small sample size of the majority of studies is a limiting factor for the reliability of previous findings. In conclusion, evidence for an effect of TMS on positive symptoms was mixed. Since most of the studies were performed in patients with auditory verbal hallucinations, further research of TMS for other positive symptoms including thought disorder and delusions is warranted.
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Affiliation(s)
- Taylor Marzouk
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA.,Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, New York, USA.,Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, New York, USA
| | - Stephanie Winkelbeiner
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA, .,Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, New York, USA, .,Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, New York, USA, .,Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland,
| | - Heela Azizi
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA.,Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, New York, USA.,Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, New York, USA
| | - Anil K Malhotra
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA.,Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, New York, USA.,Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, New York, USA
| | - Philipp Homan
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA.,Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, New York, USA.,Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, New York, USA
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14
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Brandt SJ, Oral HY, Arellano-Bravo C, Plawecki MH, Hummer TA, Francis MM. Repetitive Transcranial Magnetic Stimulation as a Therapeutic and Probe in Schizophrenia: Examining the Role of Neuroimaging and Future Directions. Neurotherapeutics 2021; 18:827-844. [PMID: 33844154 PMCID: PMC8423934 DOI: 10.1007/s13311-021-01046-1] [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] [Accepted: 03/23/2021] [Indexed: 12/31/2022] Open
Abstract
Schizophrenia is a complex condition associated with perceptual disturbances, decreased motivation and affect, and disrupted cognition. Individuals living with schizophrenia may experience myriad poor outcomes, including impairment in independent living and function as well as decreased life expectancy. Though existing treatments may offer benefit, many individuals still experience treatment resistant and disabling symptoms. In light of the negative outcomes associated with schizophrenia and the limitations in currently available treatments, there is a significant need for novel therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate the activity of discrete cortical regions, allowing direct manipulation of local brain activation and indirect manipulation of the target's associated neural networks. rTMS has been studied in schizophrenia for the treatment of auditory hallucinations, negative symptoms, and cognitive deficits, with mixed results. The field's inability to arrive at a consensus on the use rTMS in schizophrenia has stemmed from a variety of issues, perhaps most notably the significant heterogeneity amongst existing trials. In addition, it is likely that factors specific to schizophrenia, rather than the rTMS itself, have presented barriers to the interpretation of existing results. However, advances in approaches to rTMS as a biologic probe and therapeutic, many of which include the integration of neuroimaging with rTMS, offer hope that this technology may still play a role in improving the understanding and treatment of schizophrenia.
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Affiliation(s)
- Stephen J Brandt
- Indiana University School of Medicine, Department of Psychiatry, 355W 16 St., Indianapolis, IN, USA
| | - Halimah Y Oral
- Indiana University School of Medicine, Department of Psychiatry, 355W 16 St., Indianapolis, IN, USA
| | - Carla Arellano-Bravo
- Indiana University School of Medicine, Department of Psychiatry, 355W 16 St., Indianapolis, IN, USA
| | - Martin H Plawecki
- Indiana University School of Medicine, Department of Psychiatry, 355W 16 St., Indianapolis, IN, USA
| | - Tom A Hummer
- Indiana University School of Medicine, Department of Psychiatry, 355W 16 St., Indianapolis, IN, USA
| | - Michael M Francis
- Indiana University School of Medicine, Department of Psychiatry, 355W 16 St., Indianapolis, IN, USA.
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15
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Homan S, Muscat W, Joanlanne A, Marousis N, Cecere G, Hofmann L, Ji E, Neumeier M, Vetter S, Seifritz E, Dierks T, Homan P. Treatment effect variability in brain stimulation across psychiatric disorders: A meta-analysis of variance. Neurosci Biobehav Rev 2021; 124:54-62. [PMID: 33482243 DOI: 10.1016/j.neubiorev.2020.11.033] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 10/26/2020] [Accepted: 11/29/2020] [Indexed: 02/07/2023]
Abstract
Noninvasive brain stimulation methods such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are promising add-on treatments for a number of psychiatric conditions. Yet, some of the initial excitement is wearing off. Randomized controlled trials (RCT) have found inconsistent results. This inconsistency is suspected to be the consequence of variation in treatment effects and solvable by identifying responders in RCTs and individualizing treatment. However, is there enough evidence from RCTs that patients respond differently to treatment? This question can be addressed by comparing the variability in the active stimulation group with the variability in the sham group. We searched MEDLINE/PubMed and included all double-blinded, sham-controlled RCTs and crossover trials that used TMS or tDCS in adults with a unipolar or bipolar depression, bipolar disorder, schizophrenia spectrum disorder, or obsessive compulsive disorder. In accordance with the PRISMA guidelines to ensure data quality and validity, we extracted a measure of variability of the primary outcome. A total of 130 studies with 5748 patients were considered in the analysis. We calculated variance-weighted variability ratios for each comparison of active stimulation vs sham and entered them into a random-effects model. We hypothesized that treatment effect variability in TMS or tDCS would be reflected by increased variability after active compared with sham stimulation, or in other words, a variability ratio greater than one. Across diagnoses, we found only a minimal increase in variability after active stimulation compared with sham that did not reach statistical significance (variability ratio = 1.03; 95% CI, 0.97, 1.08, P = 0.358). In conclusion, this study found little evidence for treatment effect variability in brain stimulation, suggesting that the need for personalized or stratified medicine is still an open question.
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Affiliation(s)
- Stephanie Homan
- University Hospital of Psychiatry Zurich, Zurich, Switzerland; University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
| | - Whitney Muscat
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA
| | - Andrea Joanlanne
- Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA
| | | | - Giacomo Cecere
- University Hospital of Psychiatry Zurich, Zurich, Switzerland
| | - Lena Hofmann
- University Hospital of Psychiatry Zurich, Zurich, Switzerland
| | - Ellen Ji
- University Hospital of Psychiatry Zurich, Zurich, Switzerland
| | - Maria Neumeier
- University Hospital of Psychiatry Zurich, Zurich, Switzerland
| | - Stefan Vetter
- University Hospital of Psychiatry Zurich, Zurich, Switzerland
| | - Erich Seifritz
- University Hospital of Psychiatry Zurich, Zurich, Switzerland
| | - Thomas Dierks
- University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
| | - Philipp Homan
- University Hospital of Psychiatry Zurich, Zurich, Switzerland; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, New York, NY, USA; Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA.
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16
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Wagner E, Honer WG, Sommer IE, Koops S, Blumberger DM, Daskalakis ZJ, Dlabac-De Lange JJ, Bais L, Knegtering H, Aleman A, Novak T, Klirova M, Slotema C, Brunelin J, Poulet E, Kujovic M, Cordes J, Wobrock T, Siskind D, Falkai P, Schneider-Axmann T, Hasan A. Repetitive transcranial magnetic stimulation (rTMS) for schizophrenia patients treated with clozapine. World J Biol Psychiatry 2021; 22:14-26. [PMID: 32081071 DOI: 10.1080/15622975.2020.1733080] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVES Biological strategies to improve treatment efficacy in clozapine-treated patients are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) merits consideration as intervention for patients with persistent auditory hallucinations (AH) or negative symptoms (NS) not responding sufficiently to clozapine treatment. METHODS Data from 10 international RCTs of rTMS for patients being treated with clozapine were pooled. Two levels of symptomatic response were defined: improvement of ≥20% and ≥50% on study-specific primary endpoint scales. Changes in the positive and negative syndrome scale (PANSS) from baseline to endpoint assessment were also analysed. RESULTS Analyses of 131 patients did not reveal a significant difference for ≥20% and ≥50% response thresholds for improvement of AH, negative or total symptoms between active and sham rTMS groups. The number needed to treat (NNT) for an improvement in persistent AH was nine following active rTMS. PANSS scores did not improve significantly from baseline to endpoint between active and sham groups in studies investigating NS and AH. CONCLUSIONS rTMS as a treatment for persistent symptoms in clozapine-treated patients did not show a beneficial effect of active compared to sham treatment. For AH, the size of the NNTs indicates a possible beneficial effect of rTMS.
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Affiliation(s)
- Elias Wagner
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - William G Honer
- Department of Psychiatry, The University of British Columbia, Vancouver, Canada
| | - Iris E Sommer
- Department of Biomedical Sciences of Cells and Systems, Section Cognitive Neuropsychology, University Medical Center Groningen, Groningen, the Netherlands
| | - Sanne Koops
- Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Daniel M Blumberger
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada.,Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.,Department of Psychiatry, University of Toronto, Toronto, Canada
| | - Zafiris J Daskalakis
- Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada.,Campbell Family Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.,Department of Psychiatry, University of Toronto, Toronto, Canada
| | - Jozarni J Dlabac-De Lange
- Lentis Psychiatric Institute, Groningen, the Netherlands.,University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Leonie Bais
- Lentis Psychiatric Institute, Groningen, the Netherlands
| | - Henderikus Knegtering
- Lentis Psychiatric Institute, Groningen, the Netherlands.,University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - André Aleman
- Lentis Psychiatric Institute, Groningen, the Netherlands.,University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Tomas Novak
- Klecany and Third Faculty of Medicine, Charles University, National Institute of Mental Health, Prague, Czech Republic
| | - Monika Klirova
- Klecany and Third Faculty of Medicine, Charles University, National Institute of Mental Health, Prague, Czech Republic
| | - Christina Slotema
- Department of Personality Disorders, Parnassia Psychiatric Institute, the Hague, Netherlands
| | - Jerome Brunelin
- INSERM U1028, CNRS UMR 5292, CRNL, Centre Hospitalier Le Vinatier, Bron, France
| | - Emmanuel Poulet
- INSERM U1028, CNRS UMR 5292, CRNL, Centre Hospitalier Le Vinatier, Bron, France
| | - Milenko Kujovic
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University Hospital, Düsseldorf, Germany
| | - Joachim Cordes
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University Hospital, Düsseldorf, Germany
| | - Thomas Wobrock
- Department of Psychiatry and Psychotherapy, Georg-August-University, Goettingen, Germany.,Centre of Mental Health, County Hospitals Darmstadt-Dieburg, Groß-Umstadt, Germany
| | - Dan Siskind
- School of Medicine, University of Queensland, Brisbane, Australia.,Metro South Addiction and Mental Health Service, Brisbane, Australia
| | - Peter Falkai
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Thomas Schneider-Axmann
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Alkomiet Hasan
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
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17
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Briend F, Nathou C, Delcroix N, Dollfus S, Etard O. A new toolbox to compare target localizations for non-invasive brain stimulation: An application of rTMS treatment for auditory hallucinations in schizophrenia. Schizophr Res 2020; 223:305-310. [PMID: 32933813 DOI: 10.1016/j.schres.2020.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 06/24/2020] [Accepted: 09/07/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Most repetitive transcranial magnetic stimulation (rTMS) studies aiming to reduce auditory verbal hallucinations (AVH) in schizophrenia target the left temporo-parietal junction (TPJ), but the efficacy of this approach remains controversial. The observed differences in efficacy could be attributed to inaccurate target localization. Here, to precisely quantify anatomical bias induced by localization method, we developed a free open-source software (GeodesicSlicer) that computes shortest curved path (i.e. geodesic) between rTMS targets. Here we compare a personalized target with accurate anatomical criteria with a standardized target based on the 10-20 EEG system (the middle between T3 and P3 electrodes: T3P3). METHODS We compare in 69 patients with schizophrenia the geodesic distances of two approaches for rTMS target localization within the left TPJ. In addition, we characterize the personalized target according to the 10-20 EEG system. RESULTS A differential of 3 cm in term of geodesic distance between rTMS localization approaches was observed. Moreover, this personalized target to treat AVH is located at 25% in the T3-P3 axis. CONCLUSIONS This software for rTMS localization comparison demonstrates the difference between standardized and personalized rTMS target. This difference has the potential to explain a part of the dissonant clinical results found in previous rTMS studies.
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Affiliation(s)
- F Briend
- Normandie Univ, UNICAEN, ISTS, EA 7466, GIP Cyceron, 14000 Caen, France.
| | - C Nathou
- Normandie Univ, UNICAEN, ISTS, EA 7466, GIP Cyceron, 14000 Caen, France; CHU de Caen, Service de Psychiatrie adulte, Centre Esquirol, 14000 Caen, France
| | - N Delcroix
- Normandie Univ, UNICAEN, CNRS, CHU de Caen, UMS 3408, GIP Cyceron, 14000 Caen, France
| | - S Dollfus
- Normandie Univ, UNICAEN, ISTS, EA 7466, GIP Cyceron, 14000 Caen, France; CHU de Caen, Service de Psychiatrie adulte, Centre Esquirol, 14000 Caen, France
| | - O Etard
- Normandie Univ, UNICAEN, ISTS, EA 7466, GIP Cyceron, 14000 Caen, France; CHU de Caen, Service d'Explorations Fonctionnelles du Système Nerveux, 14000 Caen, France
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18
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Li J, Cao X, Liu S, Li X, Xu Y. Efficacy of repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: A meta-analysis. Psychiatry Res 2020; 290:113141. [PMID: 32521380 DOI: 10.1016/j.psychres.2020.113141] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 05/24/2020] [Indexed: 10/24/2022]
Abstract
To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) on auditory hallucinations (AH) in schizophrenia, we conducted a meta-analysis of currently available randomized control studies (RCTs). Electronic databases were searched to identify relevant literatures. Only RCTs that met the inclusion criteria were enrolled for further analysis. Standard mean difference (SMD) and 95% confidence interval (CI) values were used to evaluate the effects of rTMS. The overall robustness of the results was assessed by analyzing the influence of single studies. Publication bias was analyzed using funnel plots. Eleven eligible studies were included in this meta-analysis. Auditory hallucinations improved more in the rTMS group than in the sham group (SMD = -0.27, 95%CI = -0.51 to -0.03). However, this result was not stable after sensitivity analysis. Despite a moderate effect for rTMS on AH, future definitive trials of rTMS with rigorous processes and high-quality reporting are needed.
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Affiliation(s)
- Jingya Li
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Xiaohua Cao
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Sha Liu
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Xinrong Li
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Yong Xu
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Department of Mental Health, Shanxi Medical University, Taiyuan, China.
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19
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López-Caballero F, Martin-Trias P, Ribas-Prats T, Gorina-Careta N, Bartrés-Faz D, Escera C. Effects of cTBS on the Frequency-Following Response and Other Auditory Evoked Potentials. Front Hum Neurosci 2020; 14:250. [PMID: 32733220 PMCID: PMC7360924 DOI: 10.3389/fnhum.2020.00250] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 06/04/2020] [Indexed: 01/22/2023] Open
Abstract
The frequency-following response (FFR) is an auditory evoked potential (AEP) that follows the periodic characteristics of a sound. Despite being a widely studied biosignal in auditory neuroscience, the neural underpinnings of the FFR are still unclear. Traditionally, FFR was associated with subcortical activity, but recent evidence suggested cortical contributions which may be dependent on the stimulus frequency. We combined electroencephalography (EEG) with an inhibitory transcranial magnetic stimulation protocol, the continuous theta burst stimulation (cTBS), to disentangle the cortical contribution to the FFR elicited to stimuli of high and low frequency. We recorded FFR to the syllable /ba/ at two fundamental frequencies (Low: 113 Hz; High: 317 Hz) in healthy participants. FFR, cortical potentials, and auditory brainstem response (ABR) were recorded before and after real and sham cTBS in the right primary auditory cortex. Results showed that cTBS did not produce a significant change in the FFR recorded, in any of the frequencies. No effect was observed in the ABR and cortical potentials, despite the latter known contributions from the auditory cortex. Possible reasons behind the negative results include compensatory mechanisms from the non-targeted areas, intraindividual variability of the cTBS effectiveness, and the particular location of our target area, the primary auditory cortex.
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Affiliation(s)
- Fran López-Caballero
- Institute of Neurosciences, University of Barcelona, Barcelona, Spain.,Cognitive Neuroscience Research Group, Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain
| | - Pablo Martin-Trias
- Medical Psychology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Teresa Ribas-Prats
- Institute of Neurosciences, University of Barcelona, Barcelona, Spain.,Cognitive Neuroscience Research Group, Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain.,Institut de Recerca Sant Joan de Déu (IRSJD), Barcelona, Spain
| | - Natàlia Gorina-Careta
- Institute of Neurosciences, University of Barcelona, Barcelona, Spain.,Cognitive Neuroscience Research Group, Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain.,Institut de Recerca Sant Joan de Déu (IRSJD), Barcelona, Spain
| | - David Bartrés-Faz
- Institute of Neurosciences, University of Barcelona, Barcelona, Spain.,Medical Psychology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Carles Escera
- Institute of Neurosciences, University of Barcelona, Barcelona, Spain.,Cognitive Neuroscience Research Group, Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain.,Institut de Recerca Sant Joan de Déu (IRSJD), Barcelona, Spain
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Kennedy NI, Lee WH, Frangou S. Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: A meta-analysis of randomized controlled trials. Eur Psychiatry 2020; 49:69-77. [DOI: 10.1016/j.eurpsy.2017.12.025] [Citation(s) in RCA: 90] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/20/2017] [Accepted: 12/22/2017] [Indexed: 11/16/2022] Open
Abstract
AbstractBackgroundTranscranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have shown promise in the treatment of schizophrenia.ObjectiveTo quantify the efficacy of double-blind randomized controlled trials (RCT) of tDCS and rTMS for the positive and negative symptoms of schizophrenia and identify significant moderators relating to patient-related features and stimulation parameters.MethodsSystemic review and meta-analyses of the relevant literature published until February 1st, 2017 to assess treatment efficacy and quantify the contribution of potential moderator variables.ResultsWe identified 7 RCTs on tDCS (involving 105 participants) and 30 RCTs on rTMS (involving 768 participants). Compared to sham, tDCS improved all symptom dimensions but the effect reached significance for negative symptoms (Hedge’s g = −0.63, p = 0.02). Efficacy for positive but not negative symptoms was linearly associated with cumulative tDCS stimulation. Compared to sham, rTMS improved hallucinations (Hedge’s g = −0.51, p < 0.001) and negative symptoms (Hedge’s g = −0.49, p = 0.01) but was associated with modest, non-significant worsening of positive symptoms (Hedge’s g = 0.28, p = 0.13). Higher pulse frequency (>10 Hz), motor threshold intensity of 110%, left prefrontal cortical treatment site and trial duration over 3 weeks were associated with improvement in negative symptoms and worsening in positive symptoms (all p < 0.03).ConclusionsThe symptom dimensions in schizophrenia may respond differently to brain stimulation interventions in a way that may reflect the interaction between disease- and treatment-related mechanisms. Our findings underscore the need for further research into patient selection prior to treatment assignment and greater refinement of stimulation protocols.
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Abstract
PURPOSE OF REVIEW This current review summarizes the investigational and therapeutic applications of transcranial magnetic stimulation (TMS) in schizophrenia. RECENT FINDINGS Fairly consistent findings of an impaired cortical excitation-inhibition balance, cortical plasticity, and motor resonance have been reported in schizophrenia. Cortical connectivity impairments have also been demonstrated in motor and prefrontal brain regions. In terms of treatment, the best support is for 1-Hz TMS to the left temporoparietal cortex for the short-term treatment of persistent auditory hallucinations. High-frequency TMS to the left prefrontal cortex improves negative and cognitive symptoms, but with inconsistent and small effects. TMS combined with diverse brain mapping techniques and clinical evaluation can unravel critical brain-behavior relationships relevant to schizophrenia. These provide critical support to the conceptualization of schizophrenia as a connectopathy with anomalous cortical plasticity. Adaptive modulation of these aberrant brain networks in a neuroscience-informed manner drives short-term therapeutic gains in difficult-to-treat symptoms of schizophrenia.
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Thomas F, Bouaziz N, Gallea C, Schenin-King Andrianisaina P, Durand F, Bolloré O, Benadhira R, Isaac C, Braha-Zeitoun S, Moulier V, Valero-Cabré A, Januel D. Structural and functional brain biomarkers of clinical response to rTMS of medication-resistant auditory hallucinations in schizophrenia patients: study protocol for a randomized sham-controlled double-blind clinical trial. Trials 2019; 20:229. [PMID: 31014369 PMCID: PMC6480831 DOI: 10.1186/s13063-019-3311-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 03/21/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia. METHODS Forty-five schizophrenia patients with medication-resistant AVH will be enrolled in a double-blind randomized sham-controlled monocentric clinical trial. Patients will be assigned to a regime of 20 sessions of active or sham 1 Hz rTMS delivered twice a day, 5 days a week for 2 weeks over the left temporo-parietal junction. Response will be assessed after rTMS and patients will be classified in responders or non-responders to treatment. Magnetic resonance imaging (MRI) sessions including diffusion weighted imaging and resting-state functional MRI sequences will be recorded before the onset of the rTMS treatment and 3 days following its discontinuation. The primary outcome measure is difference in fractional anisotropy between responder and non-responder patients at baseline. Differences in resting-state functional MRI data at baseline will be also investigated between responder and non-responder groups. Clinical, neuropsychological, neurophysiological, and blood serum BDNF assessments will be performed at baseline, 3 days, 1 month, and 3 months following rTMS. DISCUSSION The aim of this research project is to identify and assess the biomarker value of MRI-based structural and functional biomarkers predicting clinical response to rTMS for AVH in schizophrenia patients. The outcome of the trial should improve patient care by offering them a novel suitable therapy and deepen our understanding on how rTMS may impact AVH and develop more effective therapies adapted to individual patient needs. TRIAL REGISTRATION ClinicalTrials.gov, NCT02755623 . Registered on 22 April 2016.
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Affiliation(s)
- Fanny Thomas
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.,Cerebral Dynamics, Plasticity and Rehabilitation Group, Frontlab, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, CNRS UMR 7225, INSERM UMRS 1127 and Université Pierre et Marie Curie, 47 boulevard de l'Hôpital, 75013, Paris, France.,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France
| | - Noomane Bouaziz
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France
| | - Cécile Gallea
- Movement Investigations and Therapeutics, MOV'IT, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, CNRS UMR 7225, INSERM UMRS 1127 and Université Pierre et Marie Curie, 47 boulevard de l'Hôpital, 75013, Paris, France
| | - Palmyre Schenin-King Andrianisaina
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France
| | - Florence Durand
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France
| | - Ombline Bolloré
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France
| | - René Benadhira
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France
| | - Clémence Isaac
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France
| | - Sonia Braha-Zeitoun
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France
| | - Virginie Moulier
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France
| | - Antoni Valero-Cabré
- Cerebral Dynamics, Plasticity and Rehabilitation Group, Frontlab, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, CNRS UMR 7225, INSERM UMRS 1127 and Université Pierre et Marie Curie, 47 boulevard de l'Hôpital, 75013, Paris, France. .,Laboratory for Cerebral Dynamics Plasticity and Rehabilitation, Boston University School of Medicine, 700 Albany Street, Boston, MA, W-702A, USA.
| | - Dominique Januel
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France. .,Laboratoire de psychopathologie et de neuropsychologie, Université Paris 8, 2 rue de la Liberté, 93526, Saint-Denis, France.
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Nathou C, Etard O, Dollfus S. Auditory verbal hallucinations in schizophrenia: current perspectives in brain stimulation treatments. Neuropsychiatr Dis Treat 2019; 15:2105-2117. [PMID: 31413576 PMCID: PMC6662171 DOI: 10.2147/ndt.s168801] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 05/24/2019] [Indexed: 12/16/2022] Open
Abstract
PURPOSE This review reports the current perspectives of brain stimulation techniques in the treatment of auditory verbal hallucinations (AVH) in schizophrenia. METHODS A systematic search of the literature in the PubMed database revealed that the most studied techniques are noninvasive techniques (NIBS), including electroconvulsive therapy (ECT), transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). RESULTS The results showed that ECT could have great clinical efficacy but is currently underused in practice perhaps due to the costs associated with its limited implementation and potential associated risks. tDCS is still poorly studied and does not demonstrate sufficiently homogeneous or conclusive results yet to prove its efficacy in the treatment of AVH. However, its safe and simple implementation allows us to recommend it to patients who are refractory to other stimulation techniques. Finally, rTMS seems to be the most efficacious NIBS to offer patients with persistent AVH as an add-on therapeutic strategy. Its implementation has a non negligible cost but can be performed by a single practitioner. Great evolution in these techniques with technological progress, robotics and computer science are currently being tested and will undoubtedly improve the clinical efficacy of these procedures, particularly towards more personalized treatments such as individual rTMS targets and intensities. There are also new techniques for deep brain stimulation based on focused ultrasound that could provide much insight into the treatment of AVH in schizophrenia. CONCLUSION This review suggests that add-on brain stimulation treatments could play a key role among the therapeutic strategies for auditory hallucinations reduction in schizophrenia.
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Affiliation(s)
- Clément Nathou
- Normandie Univ, UNICAEN, CHU de Caen, Service de Psychiatrie Adulte , Caen, F-14000, France.,Normandie Univ, UNICAEN, ISTS, EA 7466 , GIP Cyceron, Caen 14000, France
| | - Olivier Etard
- Normandie Univ, UNICAEN, ISTS, EA 7466 , GIP Cyceron, Caen 14000, France.,Normandie Univ, UNICAEN, CHU de Caen, Service des Explorations Fonctionnelles du Système Nerveux, CHU de Caen, Caen, F-14000, France
| | - Sonia Dollfus
- Normandie Univ, UNICAEN, CHU de Caen, Service de Psychiatrie Adulte , Caen, F-14000, France.,Normandie Univ, UNICAEN, ISTS, EA 7466 , GIP Cyceron, Caen 14000, France
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24
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Gałaszkiewicz J, Rębisz K, Morylowska-Topolska J, Karakuła-Juchnowicz H, Kozak G. Clozapine-resistant schizophrenia – non pharmacological augmentation methods. CURRENT PROBLEMS OF PSYCHIATRY 2018. [DOI: 10.1515/cpp-2017-0021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Abstract
Clozapine is the drug of choice for drug-resistant schizophrenia, but despite its use, 30-40% patients fail to achieve satisfactory therapeutic effects. In such situations, augmentation attempts are made by both pharmacological and non-pharmacological methods. To date, most of the work has been devoted to pharmacological strategies, much less to augemantation of clozapine with electroconvulsive therapy (C+ECT), transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS).
Aim: The aim of the work is to present biological, non-pharmacological augmentation treatment methods with clozapine.
Material and methods: A review of the literature on non-pharmacological augmentation treatment methods with clozapine was made. PubMed database was searched using key words: drug-resistant schizophrenia, clozapine, ECT, transcranial magnetic stimulation, transcranial electrical stimulation and time descriptors: 1980-2017.
Results: Most studies on the possibility of increasing the efficacy of clozapine was devoted to combination therapy with clozapine + electric treatments. They have shown improved efficacy when using these two methods simultaneously from 37.5 to 100%. The only randomized trial so far has also confirmed the effectiveness of this procedure. Despite the described side effects of tachycardia or prolonged seizures, most studies indicate the safety and efficacy of combined use of clozapine and electroconvulsive therapy. Transcranial magnetic stimulation also appears to be a safe method in patients treated with clozapine. However, further research is needed before ECT can be included in standard TRS treatment algorithms. The data for combining transcranial electrical stimulation with clozapine, come only from descriptions of cases and need to be confirmed in controlled studies.
Conclusions: The results of studies on the possibility of increasing the effectiveness of clozapine using biological non-pharmacological treatment methods indicate a potentially beneficial effect of this type of methods in breaking the super-resistance in schizophrenia. Combination of clozapine and ECT can be considered as the most recommended strategy among these treatment methods.
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Affiliation(s)
- Joanna Gałaszkiewicz
- I Department of Psychiatry, Psychotherapy and Early Intervention , Medical University of Lublin
| | - Krzysztof Rębisz
- I Department of Psychiatry, Psychotherapy and Early Intervention , Medical University of Lublin
| | | | | | - Gustaw Kozak
- I Department of Psychiatry, Psychotherapy and Early Intervention , Medical University of Lublin
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Dollfus S, Jaafari N, Guillin O, Trojak B, Plaze M, Saba G, Nauczyciel C, Montagne Larmurier A, Chastan N, Meille V, Krebs MO, Ayache SS, Lefaucheur JP, Razafimandimby A, Leroux E, Morello R, Marie Batail J, Brazo P, Lafay N, Wassouf I, Harika-Germaneau G, Guillevin R, Guillevin C, Gerardin E, Rotharmel M, Crépon B, Gaillard R, Delmas C, Fouldrin G, Laurent G, Nathou C, Etard O. High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia. Schizophr Bull 2018; 44:505-514. [PMID: 29897597 PMCID: PMC5890503 DOI: 10.1093/schbul/sbx127] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. METHODS Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). RESULTS The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. DISCUSSION This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.
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Affiliation(s)
- Sonia Dollfus
- CHU de Caen, Service de Psychiatrie, Centre Esquirol, Caen, France,Normandie Univ, UNICAEN, Imagerie et Strategies Therapeutiques de la schizophrenie (ISTS), EA4766, Caen, France,To whom correspondence should be addressed; CHU de Caen, Service de Psychiatrie, Centre Esquirol, Caen F-14000, France, tel: +332 3106 5018; Fax: +332 3106 4789; e-mail: , http://www.ists.cyceron.fr/
| | - Nemat Jaafari
- Centre Hospitalier Henri Laborit, Poitiers, France,Laboratoire expérimental et clinique en Neurosciences, Univ Poitiers, Poitiers, France
| | - Olivier Guillin
- Department of Psychiatry, CH Le Rouvray, Sotteville les Rouen, France,INSERM U 1079, University of Medicine, Rouen, France,CHU Charles Nicolle, Rouen, France
| | - Benoit Trojak
- CHU de Dijon, Service de psychiatrie et d’addictologie, Dijon, France
| | - Marion Plaze
- Centre Hospitalier Sainte-Anne, Service Hospitalo-Universitaire, Paris, France
| | - Ghassen Saba
- Henri Mondor Hospital, Paris-Est Créteil University, Créteil, France
| | | | | | | | - Vincent Meille
- CHU de Dijon, Service de psychiatrie et d’addictologie, Dijon, France
| | - Marie-Odile Krebs
- Centre Hospitalier Sainte-Anne, Service Hospitalo-Universitaire, Paris, France
| | - Samar S Ayache
- Clinical Neurophysiology Unit, Department of Physiology, Henri Mondor Hospital, Paris-Est Créteil University, Créteil, France
| | - Jean Pascal Lefaucheur
- Clinical Neurophysiology Unit, Department of Physiology, Henri Mondor Hospital, Paris-Est Créteil University, Créteil, France
| | - Annick Razafimandimby
- Normandie Univ, UNICAEN, Imagerie et Strategies Therapeutiques de la schizophrenie (ISTS), EA4766, Caen, France
| | - Elise Leroux
- Normandie Univ, UNICAEN, Imagerie et Strategies Therapeutiques de la schizophrenie (ISTS), EA4766, Caen, France
| | - Rémy Morello
- CHU de Caen, Unité de biostatistiques et recherche clinique, Caen, France
| | | | - Perrine Brazo
- CHU de Caen, Service de Psychiatrie, Centre Esquirol, Caen, France,Normandie Univ, UNICAEN, Imagerie et Strategies Therapeutiques de la schizophrenie (ISTS), EA4766, Caen, France
| | | | - Issa Wassouf
- Centre Hospitalier Henri Laborit, Poitiers, France
| | | | | | | | | | - Maud Rotharmel
- Department of Psychiatry, CH Le Rouvray, Sotteville les Rouen, France
| | - Benoit Crépon
- Centre Hospitalier Sainte-Anne, Service de neurophysiologie clinique, Paris, France
| | - Raphael Gaillard
- Centre Hospitalier Sainte-Anne, Service Hospitalo-Universitaire, Paris, France
| | - Christophe Delmas
- Department of Psychiatry, CH Le Rouvray, Sotteville les Rouen, France
| | | | - Guillaume Laurent
- Department of Psychiatry, CH Le Rouvray, Sotteville les Rouen, France
| | - Clément Nathou
- CHU de Caen, Service de Psychiatrie, Centre Esquirol, Caen, France,Normandie Univ, UNICAEN, Imagerie et Strategies Therapeutiques de la schizophrenie (ISTS), EA4766, Caen, France,Department of Psychiatry, CH Le Rouvray, Sotteville les Rouen, France
| | - Olivier Etard
- Normandie Univ, UNICAEN, Imagerie et Strategies Therapeutiques de la schizophrenie (ISTS), EA4766, Caen, France,CHU de Caen, Service des explorations fonctionnelles du système nerveux, Caen, France
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26
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He H, Lu J, Yang L, Zheng J, Gao F, Zhai Y, Feng J, Fan Y, Ma X. Repetitive transcranial magnetic stimulation for treating the symptoms of schizophrenia: A PRISMA compliant meta-analysis. Clin Neurophysiol 2017; 128:716-724. [PMID: 28315614 DOI: 10.1016/j.clinph.2017.02.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 01/23/2017] [Accepted: 02/13/2017] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To explore the efficacies of 1-Hz (low frequency) and 10-Hz (high frequency) repetitive transcranial magnetic stimulation (rTMS) in treating auditory hallucinations and negative symptoms of schizophrenia, respectively. METHODS Electronic databases were searched to identify relevant literature. Standard mean difference (SMD) and 95% confidence interval (CI) values were used to evaluate the effects of rTMS. The stability and sensitivity of the results, the source of heterogeneity, and the recommended grade of the evidence were also analyzed. RESULTS Thirteen studies of 1-Hz rTMS were included. The auditory hallucinations improved more in the rTMS group than in the sham group (SMD=-0.29, 95%CI=-0.57 to -0.01). However, this result was not stable after sensitivity analysis, and publication bias had a substantial impact on the results. Meta-analysis performed for seven studies of 10-Hz rTMS found that improvement of negative symptoms did not differ significantly between the real rTMS and sham groups. Finally, the grade of evidence for this meta-analysis was found to be low. CONCLUSION Although there may appear to be a therapeutic effect for 1-Hz rTMS on auditory hallucinations of schizophrenia, this needs to be confirmed by large-scale randomized controlled trials before this finding can be recommended in clinical practice. SIGNIFICANCE 1-Hz rTMS might have an effect on auditory hallucinations of schizophrenia.
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Affiliation(s)
- Hairong He
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Jun Lu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Lihong Yang
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Jie Zheng
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Fan Gao
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yajing Zhai
- Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Junqin Feng
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yajuan Fan
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Xiancang Ma
- Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
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27
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Paillère-Martinot ML, Galinowski A, Plaze M, Andoh J, Bartrés-Faz D, Bellivier F, Lefaucheur JP, Rivière D, Gallarda T, Martinot JL, Artiges E. Active and placebo transcranial magnetic stimulation effects on external and internal auditory hallucinations of schizophrenia. Acta Psychiatr Scand 2017; 135:228-238. [PMID: 27987221 DOI: 10.1111/acps.12680] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/14/2016] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. METHOD Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. RESULTS A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. CONCLUSIONS A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested.
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Affiliation(s)
- M-L Paillère-Martinot
- AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France.,INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Université Paris Descartes, Paris, France.,University Paris-Sud, and University Paris-Saclay, Orsay, France
| | - A Galinowski
- INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Université Paris Descartes, Paris, France.,University Paris-Sud, and University Paris-Saclay, Orsay, France.,SHU Department of Psychiatry, Sainte-Anne Hospital, Paris, France
| | - M Plaze
- INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Université Paris Descartes, Paris, France.,SHU Department of Psychiatry, Sainte-Anne Hospital, Paris, France
| | - J Andoh
- INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - D Bartrés-Faz
- INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Department of Psychiatry and Clinical Psychobiology, Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - F Bellivier
- AP-HP, Department of Psychiatry, Henri Mondor-Albert Chenevier Hospital, Créteil, France.,INSERM, U1144, Université Paris Diderot, Paris, France
| | - J-P Lefaucheur
- AP-HP, Physiology Department, Henri Mondor - Albert Chenevier Hospital, Créteil, France.,Université Paris 12, Créteil, France
| | - D Rivière
- CEA, LNAO, NeuroSpin, Gif-sur-Yvette, France
| | - T Gallarda
- Université Paris Descartes, Paris, France.,SHU Department of Psychiatry, Sainte-Anne Hospital, Paris, France
| | - J-L Martinot
- INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Université Paris Descartes, Paris, France.,University Paris-Sud, and University Paris-Saclay, Orsay, France
| | - E Artiges
- INSERM, U 1000, Research unit 'Imaging & Psychiatry', Service Hospitalier Frédéric Joliot, Orsay, France.,Université Paris Descartes, Paris, France.,University Paris-Sud, and University Paris-Saclay, Orsay, France.,Psychiatry Department 91G16, GH Nord Essonne, Orsay, France
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Thomas F, Moulier V, Valéro-Cabré A, Januel D. Brain connectivity and auditory hallucinations: In search of novel noninvasive brain stimulation therapeutic approaches for schizophrenia. Rev Neurol (Paris) 2016; 172:653-679. [PMID: 27742234 DOI: 10.1016/j.neurol.2016.09.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Revised: 06/10/2016] [Accepted: 09/19/2016] [Indexed: 12/14/2022]
Abstract
Auditory verbal hallucinations (AVH) are among the most characteristic symptoms of schizophrenia and have been linked to likely disturbances of structural and functional connectivity within frontal, temporal, parietal and subcortical networks involved in language and auditory functions. Resting-state functional magnetic resonance imaging (fMRI) has shown that alterations in the functional connectivity activity of the default-mode network (DMN) may also subtend hallucinations. Noninvasive neurostimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) have the ability to modulate activity of targeted cortical sites and their associated networks, showing a high potential for modulating altered connectivity subtending schizophrenia. Notwithstanding, the clinical benefit of these approaches remains weak and variable. Further studies in the field should foster a better understanding concerning the status of networks subtending AVH and the neural impact of rTMS in relation with symptom improvement. Additionally, the identification and characterization of clinical biomarkers able to predict response to treatment would be a critical asset allowing better care for patients with schizophrenia.
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Affiliation(s)
- F Thomas
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202, avenue Jean-Jaurès, 93332 Neuilly-sur-Marne cedex, France.
| | - V Moulier
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202, avenue Jean-Jaurès, 93332 Neuilly-sur-Marne cedex, France
| | - A Valéro-Cabré
- UMR 7225 CRICM CNRS, Université Pierre-et-Marie-Curie, Groupe Hospitalier Pitié-Salpêtrière, 47, boulevard de l'Hôpital, 75013 Paris, France; Université Pierre-et-Marie-Curie, CNRS UMR 7225-Inserm UMRS S975, Centre de Recherche de l'Institut du Cerveau et la Moelle (ICM), 75013 Paris, France; Laboratory for Cerebral Dynamics Plasticity & Rehabilitation, Boston University School of Medicine, Boston, MA, USA; Cognitive Neuroscience and Information Technology Research Program, Open University of Catalonia (UOC), Barcelona, Spain
| | - D Januel
- Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202, avenue Jean-Jaurès, 93332 Neuilly-sur-Marne cedex, France
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Hasan A, Strube W, Palm U, Wobrock T. Repetitive Noninvasive Brain Stimulation to Modulate Cognitive Functions in Schizophrenia: A Systematic Review of Primary and Secondary Outcomes. Schizophr Bull 2016; 42 Suppl 1:S95-S109. [PMID: 27460623 PMCID: PMC4960427 DOI: 10.1093/schbul/sbv158] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Despite many years of research, there is still an urgent need for new therapeutic options for the treatment of cognitive deficits in schizophrenia. Noninvasive brain stimulation (NIBS) has been proposed to be such a novel add-on treatment option. The main objective of this review was to systematically evaluate the cognitive effects of repetitive NIBS in schizophrenia. As most studies have not been specifically designed to investigate cognition as primary outcome, we have focused on both, primary and secondary outcomes. The PubMed/MEDLINE database (1985-2015) was systematically searched for interventional studies investigating the effects of repetitive NIBS on schizophrenia symptoms. All interventional clinical trials using repetitive transcranial stimulation, transcranial theta burst stimulation, and transcranial direct current stimulation for the treatment of schizophrenia were extracted and analyzed with regard to cognitive measures as primary or secondary outcomes. Seventy-six full-text articles were assessed for eligibility of which 33 studies were included in the qualitative synthesis. Of these 33 studies, only 4 studies included cognition as primary outcome, whereas 29 studies included cognitive measures as secondary outcomes. A beneficial effect of frontal NIBS could not be clearly established. No evidence for a cognitive disruptive effect of NIBS (temporal lobe) in schizophrenia could be detected. Finally, a large heterogeneity between studies in terms of inclusion criteria, stimulation parameters, applied cognitive measures, and follow-up intervals was observed. This review provides the first systematic overview regarding cognitive effects of repetitive NIBS in schizophrenia.
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Affiliation(s)
- Alkomiet Hasan
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany;
| | - Wolfgang Strube
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
| | - Ulrich Palm
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany
| | - Thomas Wobrock
- County Hospitals Darmstadt-Dieburg, Groß-Umstadt, Germany; Department of Psychiatry and Psychotherapy, Georg-August-University, Göttingen, Germany
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Arumugham SS, Thirthalli J, Andrade C. Efficacy and safety of combining clozapine with electrical or magnetic brain stimulation in treatment-refractory schizophrenia. Expert Rev Clin Pharmacol 2016; 9:1245-52. [PMID: 27322602 DOI: 10.1080/17512433.2016.1200971] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Shyam Sundar Arumugham
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India
| | - Jagadisha Thirthalli
- Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India
| | - Chittaranjan Andrade
- Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India
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31
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Dollfus S, Lecardeur L, Morello R, Etard O. Placebo Response in Repetitive Transcranial Magnetic Stimulation Trials of Treatment of Auditory Hallucinations in Schizophrenia: A Meta-Analysis. Schizophr Bull 2016; 42:301-8. [PMID: 26089351 PMCID: PMC4753589 DOI: 10.1093/schbul/sbv076] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Several meta-analyses have assessed the response of patients with schizophrenia with auditory verbal hallucinations (AVH) to treatment with repetitive transcranial magnetic stimulation (rTMS); however, the placebo response has never been explored. Typically observed in a therapeutic trial, the placebo effect may have a major influence on the effectiveness of rTMS. The purpose of this meta-analysis is to evaluate the magnitude of the placebo effect observed in controlled studies of rTMS treatment of AVH, and to determine factors that can impact the magnitude of this placebo effect, such as study design considerations and the type of sham used.The study included twenty-one articles concerning 303 patients treated by sham rTMS. A meta-analytic method was applied to obtain a combined, weighted effect size, Hedges's g. The mean weighted effect size of the placebo effect across these 21 studies was 0.29 (P < .001). Comparison of the parallel and crossover studies revealed distinct results for each study design; placebo has a significant effect size in the 13 parallel studies (g = 0.44, P < 10(-4)), but not in the 8 crossover studies (g = 0.06, P = .52). In meta-analysis of the 13 parallel studies, the 45° position coil showed the highest effect size. Our results demonstrate that placebo effect should be considered a major source of bias in the assessment of rTMS efficacy. These results fundamentally inform the design of further controlled studies, particularly with respect to studies of rTMS treatment in psychiatry.
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Affiliation(s)
| | - Laurent Lecardeur
- CHU de Caen, Service de Psychiatrie, Centre Esquirol, Caen, F-14000, France;,CNRS, UMR 6301, ISTCT, ISTS Group, GIP Cyceron, Caen, F-14074, France
| | - Rémy Morello
- CHU de Caen, Unité de Biostatistique et de Recherche Clinique, F-14000, France
| | - Olivier Etard
- UCBN, UFR de Médecine, Caen, F-14000, France;,CHU de Caen, Laboratoire d’Explorations Fonctionnelles Neurologiques, Caen, F-14000, France
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Koops S, van Dellen E, Schutte MJL, Nieuwdorp W, Neggers SFW, Sommer IEC. Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial. Schizophr Bull 2016; 42. [PMID: 26221051 PMCID: PMC4681555 DOI: 10.1093/schbul/sbv100] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Auditory verbal hallucinations (AVH) in schizophrenia are resistant to antipsychotic medication in approximately 25% of patients. Treatment with repetitive transcranial magnetic stimulation (rTMS) for refractory AVH has shown varying results. A stimulation protocol using continuous theta burst rTMS (TB-rTMS) showed high efficacy in open label studies. We tested TB-rTMS as a treatment strategy for refractory AVH in a double-blind, placebo-controlled trial. METHODS Seventy-one patients with AVH were randomly allocated to TB-rTMS or placebo treatment. They received 10 TB-rTMS or sham treatments over the left temporoparietal cortex in consecutive days. AVH severity was assessed at baseline, end of treatment and follow-up using the Psychotic Symptom Rating Scale (PSYRATS) and the Auditory Hallucinations Rating Scale (AHRS). Other schizophrenia-related symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS Seven patients dropped out before completing the study. In the remaining 64, AVH improved significantly after treatment in both groups as measured with both PSYRATS and AHRS. PANSS positive and general subscores also decreased, but the negative subscores did not. However, improvement did not differ significantly between the TB-rTMS and the placebo group on any outcome measure. CONCLUSIONS Symptom reduction could be achieved in patients with medication-resistant hallucinations, even within 1 week time. However, as both groups showed similar improvement, effects were general (ie, placebo-effects) rather than specific to treatment with continuous TB-rTMS. Our findings highlight the importance of double-blind trials including a sham-control condition to assess efficacy of new treatments such as TMS.
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Affiliation(s)
- Sanne Koops
- Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Utrecht, The Netherlands
| | - Edwin van Dellen
- Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands;,Brain Center Rudolf Magnus, Utrecht, The Netherlands
| | - Maya J. L. Schutte
- Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands;,Brain Center Rudolf Magnus, Utrecht, The Netherlands
| | - Wendy Nieuwdorp
- Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands;,Brain Center Rudolf Magnus, Utrecht, The Netherlands
| | - Sebastiaan F. W. Neggers
- Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands;,Brain Center Rudolf Magnus, Utrecht, The Netherlands
| | - Iris E. C. Sommer
- Psychiatry Department, University Medical Center Utrecht, Utrecht, The Netherlands;,Brain Center Rudolf Magnus, Utrecht, The Netherlands
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33
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Cortical Anatomical Variations and Efficacy of rTMS in the Treatment of Auditory Hallucinations. Brain Stimul 2015; 8:1162-7. [DOI: 10.1016/j.brs.2015.06.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2014] [Revised: 04/23/2015] [Accepted: 06/07/2015] [Indexed: 11/20/2022] Open
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Kubera KM, Barth A, Hirjak D, Thomann PA, Wolf RC. Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges. Front Syst Neurosci 2015; 9:131. [PMID: 26528145 PMCID: PMC4601083 DOI: 10.3389/fnsys.2015.00131] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 09/07/2015] [Indexed: 12/12/2022] Open
Abstract
This mini-review focuses on noninvasive brain stimulation techniques as an augmentation method for the treatment of persistent auditory verbal hallucinations (AVH) in patients with schizophrenia. Paradigmatically, we place emphasis on transcranial magnetic stimulation (TMS). We specifically discuss rationales of stimulation and consider methodological questions together with issues of phenotypic diversity in individuals with drug-refractory and persistent AVH. Eventually, we provide a brief outlook for future investigations and treatment directions. Taken together, current evidence suggests TMS as a promising method in the treatment of AVH. Low-frequency stimulation of the superior temporal cortex (STC) may reduce symptom severity and frequency. Yet clinical effects are of relatively short duration and effect sizes appear to decrease over time along with publication of larger trials. Apart from considering other innovative stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), and optimizing stimulation protocols, treatment of AVH using noninvasive brain stimulation will essentially rely on accurate identification of potential responders and non-responders for these treatment modalities. In this regard, future studies will need to consider distinct phenotypic presentations of AVH in patients with schizophrenia, together with the putative functional neurocircuitry underlying these phenotypes.
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Affiliation(s)
- Katharina M Kubera
- Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg Heidelberg, Germany
| | - Anja Barth
- Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg Heidelberg, Germany
| | - Dusan Hirjak
- Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg Heidelberg, Germany
| | - Philipp A Thomann
- Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg Heidelberg, Germany
| | - Robert C Wolf
- Center for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg Heidelberg, Germany ; Department of Psychiatry, Psychotherapy and Psychosomatics, Saarland University Homburg, Germany
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35
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Dougall N, Maayan N, Soares‐Weiser K, McDermott LM, McIntosh A, Cochrane Schizophrenia Group. Transcranial magnetic stimulation (TMS) for schizophrenia. Cochrane Database Syst Rev 2015; 2015:CD006081. [PMID: 26289586 PMCID: PMC9395125 DOI: 10.1002/14651858.cd006081.pub2] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND People with schizophrenia often experience symptoms which fail to fully respond to antipsychotic medication. Transcranial magnetic stimulation (TMS) has been proposed as a new treatment for people with schizophrenia, especially those who experience persistent auditory hallucinations. OBJECTIVES To estimate the effects of TMS alone, compared with sham TMS or with 'standard management' and any other comparison interventions in reducing psychotic symptoms associated with schizophrenia. SEARCH METHODS We searched the Cochrane Schizophrenia Group Trials Register (June 2006, June 2008, April 2013). This register is compiled by methodical searches of MEDLINE, EMBASE, BIOSIS, CINAHL, Dissertation abstracts, LILACS, PSYNDEX, PsycINFO, RUSSMED, and Sociofile, and is supplemented with handsearching of relevant journals and numerous conference proceedings. SELECTION CRITERIA We included all randomised controlled trials recruiting at least five participants and comparing TMS with sham TMS or any other treatment for people with schizophrenia. DATA COLLECTION AND ANALYSIS We extracted data independently. For dichotomous data we calculated relative risks (RRs) and their 95% confidence intervals (CIs). For continuous data, we calculated mean differences (MD) and 95% CI. We used a fixed-effect model. We assessed overall quality of the evidence using the GRADE approach. MAIN RESULTS We included 41 studies with 1473 participants in the review. We found significant differences in favour of temporoparietal TMS compared to sham TMS for global state measured on the CGI scale (7 RCTs, n = 224, MD -0.5, 95% CI -0.76 to -0.23, very low-quality evidence) and positive symptoms measured on the PANSS scale (5 RCTs, n = 127, MD -6.09, 95% CI -10.95 to -1.22, very low-quality evidence). Participants experienced significantly more headaches in the temporoparietal TMS group (10 RCTs, n = 392, RR 2.65, 95% CI 1.56 to 4.50, very low-quality evidence). However, no more participants left the study early from the TMS group than from the sham group (very low-quality evidence). Cognitive state was assessed using 39 different measures, and all were equivocal (very low-quality evidence).We included only two trials which compared temporoparietal TMS with standard treatment. In both trials the participants received first- and second-generation antipsychotic medication in both treatment groups, therefore TMS was used an adjunctive therapy to medication. We found no significant differences in the number of participants that showed clinical improvement in global state (1 RCT, n = 100, RR 1.19, 95% CI 0.91 to 1.57) or left the study early (2 RCTs, n = 140, RR 0.33, 95% CI 0.08 to 1.46) (both very low-quality evidence). No studies reported on global state score, mental state, cognitive state and adverse effects.For prefrontal TMS compared to sham TMS, global state was measured on three different scales, all of which presented equivocal results (very low quality evidence). We could not pool data for mental state on the PANSS scale due to high heterogeneity. Cognitive state was assessed using 19 different measures, with 15/19 being equivocal (very low-quality evidence). Prefrontal TMS caused more headaches (6 RCTs, n = 164, RR 2.77, 95% CI 1.22 to 6.26, very low-quality evidence) but there was no difference in the number of participants leaving the study early (very low-quality evidence). No studies reported data for clinical improvement.We found a significant difference in favour of prefrontal theta burst stimulation TMS compared to sham TMS for mental state on the PANNS scale (3 RCTs, n = 108, MD -5.71, 95% CI -9.32 to -2.10, very low evidence). We found no difference for clinical improvement, cognitive state, number of headaches, and leaving the study early (very low-quality evidence).None of the included studies reported satisfaction with care. AUTHORS' CONCLUSIONS Based on this review, there is insufficient evidence to support or refute the use of TMS to treat symptoms of schizophrenia. Although some evidence suggests that TMS, and in particular temporoparietal TMS, may improve certain symptoms (such as auditory hallucinations and positive symptoms of schizophrenia) compared to sham TMS, the results were not robust enough to be unequivocal across the assessment measures used. There was insufficient evidence to suggest any added benefit with TMS used as an adjunctive therapy to antipsychotic medication.The overall quality of evidence was graded as very low due to risk of bias, and this was accompanied by an imprecision in estimates due to the relatively small number of participants in the studies. Thus, consideration is required in improving the quality of trial processes, as well as the quality of reporting of ongoing and future TMS trials, so as to facilitate accurate future judgements in assessing risk of bias. Differences in TMS techniques in relation to stimulation intensity, stimulation length, brain areas stimulated and variations in the design of sham TMS all contributed to the heterogeneity of study findings and limited the interpretation and applicability of the results. In addition, the trials assessed their outcomes with a variety of scales, and usable data were limited. Therefore, to better evaluate the treatment effects of TMS in people with schizophrenia, we favour the use of standardised treatment protocols and outcome measures.
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Affiliation(s)
- Nadine Dougall
- University of StirlingNMAHP Research UnitUnit 13 Scion HouseStirling University Innovation ParkStirlingUKFK9 4NF
| | - Nicola Maayan
- Enhance Reviews LtdCentral Office, Cobweb BuildingsThe Lane, LyfordWantageUKOX12 0EE
| | - Karla Soares‐Weiser
- Enhance Reviews LtdCentral Office, Cobweb BuildingsThe Lane, LyfordWantageUKOX12 0EE
| | - Lisa M McDermott
- King's College LondonPrimary Care and Public Health Sciences42 Weston StreetLondonUKSE1 3QD
| | - Andrew McIntosh
- University of Edinburgh, Royal Edinburgh HospitalEdinburghUKEH10 5HF
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Ray P, Sinha VK, Tikka SK. Adjuvant low-frequency rTMS in treating auditory hallucinations in recent-onset schizophrenia: a randomized controlled study investigating the effect of high-frequency priming stimulation. Ann Gen Psychiatry 2015; 14:8. [PMID: 25699086 PMCID: PMC4333242 DOI: 10.1186/s12991-015-0046-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 01/27/2015] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) has been found to be effective in reducing frequency and duration of auditory verbal hallucinations (AVH). Priming stimulation, which involves high-frequency rTMS stimulation followed by low-frequency rTMS, has been shown to markedly enhance the neural response to the low-frequency stimulation train. However, this technique has not been investigated in recent onset schizophrenia patients. The aim of this randomized controlled study was to investigate whether the effects of rTMS on AVH can be enhanced with priming rTMS in recent onset schizophrenia patients. METHODS Forty recent onset schizophrenia patients completed the study. Patients were randomized over two groups: one receiving low-frequency rTMS preceded by priming and another receiving low-frequency rTMS without priming. Both treatments were directed at the left temporo-parietal region. The severity of AVH and other psychotic symptoms were assessed with the auditory hallucination subscale (AHRS) of the Psychotic Symptom Rating Scales (PSYRATS), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI). RESULTS We found that all the scores of these ratings significantly reduced over time (i.e. baseline through 1, 2, 4 and 6 weeks) in both the treatment groups. We found no difference between the two groups on all measures, except for significantly greater improvement on loudness of AVH in the group with priming stimulation during the follow-ups (F = 2.72; p < .05). CONCLUSIONS We conclude that low-frequency rTMS alone and high-frequency priming of low-frequency rTMS do not elicit significant differences in treatment of overall psychopathology, particularly AVH when given in recent onset schizophrenia patients. Add on priming however, seems to be particularly better in faster reduction in loudness of AVH.
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Affiliation(s)
- Prasenjit Ray
- Department of Psychiatry, Burdwan Medical College, Burdwan, 713101 West Bengal India
| | - Vinod Kumar Sinha
- KS Mani Center for Cognitive Neurosciences and Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi, 834006 Jharkhand India
| | - Sai Krishna Tikka
- KS Mani Center for Cognitive Neurosciences and Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi, 834006 Jharkhand India
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Bais L, Vercammen A, Stewart R, van Es F, Visser B, Aleman A, Knegtering H. Short and long term effects of left and bilateral repetitive transcranial magnetic stimulation in schizophrenia patients with auditory verbal hallucinations: a randomized controlled trial. PLoS One 2014; 9:e108828. [PMID: 25329799 PMCID: PMC4203691 DOI: 10.1371/journal.pone.0108828] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 07/15/2014] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation. METHODS In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months. RESULTS The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups. CONCLUSION We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors predicting individual response. TRIAL REGISTRATION Dutch Trial Register NTR1813.
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Affiliation(s)
- Leonie Bais
- University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN NeuroImaging Center, Groningen, The Netherlands
- Lentis Psychiatric Institute, Groningen, The Netherlands
- * E-mail:
| | - Ans Vercammen
- Australian Catholic University, Strathfield, Australia
| | - Roy Stewart
- University of Groningen, University Medical Center Groningen, Department of Health Sciences, Community and Occupational Medicine, Groningen, The Netherlands
| | - Frank van Es
- University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands
- University of Groningen, University Medical Center Groningen, Rob Giel Research Center, Groningen, The Netherlands
| | - Bert Visser
- University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands
| | - André Aleman
- University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN NeuroImaging Center, Groningen, The Netherlands
- University of Groningen, Department of Psychology, Groningen, The Netherlands
| | - Henderikus Knegtering
- University of Groningen, University Medical Center Groningen, Department of Neuroscience and BCN NeuroImaging Center, Groningen, The Netherlands
- Lentis Psychiatric Institute, Groningen, The Netherlands
- University of Groningen, University Medical Center Groningen, Rob Giel Research Center, Groningen, The Netherlands
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Zhang Y, Liang W, Yang S, Dai P, Shen L, Wang C. Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders: A meta-analysis. Neural Regen Res 2014; 8:2666-76. [PMID: 25206578 PMCID: PMC4146020 DOI: 10.3969/j.issn.1673-5374.2013.28.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 07/24/2013] [Indexed: 01/27/2023] Open
Abstract
OBJECTIVE This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hallucination of patients with schizophrenia spectrum disorders. DATA SOURCES Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Controlled Trials databases from January 1985 to May 2012. Key words were "transcranial magnetic stimulation", "TMS", "repetitive transcranial magnetic stimulation", and "hallucination". STUDY SELECTION Selected studies were randomized controlled trials assessing therapeutic efficacy of repetitive transcranial magnetic stimulation for hallucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hallucination in schizophrenia spectrum disorders. Control groups received sham stimulation. MAIN OUTCOME MEASURES The primary outcome was total scores of Auditory Hallucinations Rating Scale, Auditory Hallucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hallucination item, and Hallucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. RESULTS Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. All data were completely effective, involving 398 patients. Overall mean weighted effect size for repetitive transcranial magnetic stimulation versus sham stimulation was statistically significant (MD = -0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P = 0.005). No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for positive or negative symptoms. Compared with sham stimulation, active repetitive transcranial magnetic stimulation had equivocal outcome in cognitive function and commonly caused headache and facial muscle twitching. CONCLUSION Repetitive transcranial magnetic stimulation is a safe and effective treatment for auditory hallucination in schizophrenia spectrum disorders.
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Affiliation(s)
- Yingli Zhang
- Psychological Counseling Center, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan Province, China
| | - Wei Liang
- Department of Clinical Psychology, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan Province, China
| | - Shichang Yang
- Department of Psychology, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
| | - Ping Dai
- Library of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lijuan Shen
- Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Changhong Wang
- Department of Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, Henan Province, China
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Review of the efficacy of transcranial magnetic stimulation for auditory verbal hallucinations. Biol Psychiatry 2014; 76:101-10. [PMID: 24315551 DOI: 10.1016/j.biopsych.2013.09.038] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 09/05/2013] [Accepted: 09/26/2013] [Indexed: 12/19/2022]
Abstract
With an increase of the number of studies exploring repetitive transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations (AVH), an update is provided on the efficacy of different paradigms. A literature search was performed from 1966 through April 2013. Twenty-five randomized controlled trials using the severity of AVH or psychosis as outcome measures were included. Standardized mean weighted effect sizes were computed; a qualitative review of the literature was performed to assess the effects of various rTMS paradigms. rTMS versus sham treatment for AVH yielded a mean weighted effect size of .44. No significant mean weighted effect size was found for the severity of psychosis (i.e., .21). For patients with medication-resistant AVH, the mean weighted effect size was .45. rTMS applied at the left temporoparietal area with a frequency of 1 Hz yielded a moderate mean weighted effect size of .63, indicating superiority of this paradigm. Various other paradigms failed to show superior effects. rTMS applied at the right temporoparietal area was not superior to sham treatment. rTMS, especially when applied at the left temporoparietal area with a frequency of 1 Hz, is effective for the treatment of AVH, including in patients with medication-resistant AVH. The results for other rTMS paradigms are disappointing thus far. A next step should be to explore the effects of rTMS in medication-free individuals, for example, during the initial phases of psychosis, and in patients with diagnoses other than schizophrenia who do not have comorbid psychotic symptoms.
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Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipović SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 2014; 125:2150-2206. [PMID: 25034472 DOI: 10.1016/j.clinph.2014.05.021] [Citation(s) in RCA: 1356] [Impact Index Per Article: 123.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 05/09/2014] [Accepted: 05/13/2014] [Indexed: 12/11/2022]
Abstract
A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.
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Affiliation(s)
- Jean-Pascal Lefaucheur
- Department of Physiology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris, Créteil, France; EA 4391, Nerve Excitability and Therapeutic Team, Faculty of Medicine, Paris Est Créteil University, Créteil, France.
| | - Nathalie André-Obadia
- Neurophysiology and Epilepsy Unit, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Bron, France; Inserm U 1028, NeuroPain Team, Neuroscience Research Center of Lyon (CRNL), Lyon-1 University, Bron, France
| | - Andrea Antal
- Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany
| | - Samar S Ayache
- Department of Physiology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris, Créteil, France; EA 4391, Nerve Excitability and Therapeutic Team, Faculty of Medicine, Paris Est Créteil University, Créteil, France
| | - Chris Baeken
- Department of Psychiatry and Medical Psychology, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium; Department of Psychiatry, University Hospital (UZBrussel), Brussels, Belgium
| | - David H Benninger
- Neurology Service, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Roberto M Cantello
- Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale "A. Avogadro", Novara, Italy
| | | | - Mamede de Carvalho
- Institute of Physiology, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal
| | - Dirk De Ridder
- Brai(2)n, Tinnitus Research Initiative Clinic Antwerp, Belgium; Department of Neurosurgery, University Hospital Antwerp, Belgium
| | - Hervé Devanne
- Department of Clinical Neurophysiology, Lille University Hospital, Lille, France; ULCO, Lille-Nord de France University, Lille, France
| | - Vincenzo Di Lazzaro
- Department of Neurosciences, Institute of Neurology, Campus Bio-Medico University, Rome, Italy
| | - Saša R Filipović
- Department of Neurophysiology, Institute for Medical Research, University of Belgrade, Beograd, Serbia
| | - Friedhelm C Hummel
- Brain Imaging and Neurostimulation (BINS) Laboratory, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Satu K Jääskeläinen
- Department of Clinical Neurophysiology, Turku University Hospital, University of Turku, Turku, Finland
| | - Vasilios K Kimiskidis
- Laboratory of Clinical Neurophysiology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Giacomo Koch
- Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia IRCCS, Rome, Italy
| | - Berthold Langguth
- Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany
| | - Thomas Nyffeler
- Perception and Eye Movement Laboratory, Department of Neurology, University Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Antonio Oliviero
- FENNSI Group, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain
| | - Frank Padberg
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
| | - Emmanuel Poulet
- Department of Emergency Psychiatry, CHU Lyon, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France; EAM 4615, Lyon-1 University, Bron, France
| | - Simone Rossi
- Brain Investigation & Neuromodulation Lab, Unit of Neurology and Clinical Neurophysiology, Department of Neuroscience, University of Siena, Siena, Italy
| | - Paolo Maria Rossini
- Brain Connectivity Laboratory, IRCCS San Raffaele Pisana, Rome, Italy; Institute of Neurology, Catholic University, Rome, Italy
| | - John C Rothwell
- Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, United Kingdom
| | | | - Hartwig R Siebner
- Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | | | - Charlotte J Stagg
- Oxford Centre for Functional MRI of the Brain (FMRIB), Department of Clinical Neurosciences, University of Oxford, United Kingdom
| | - Josep Valls-Sole
- EMG Unit, Neurology Service, Hospital Clinic, Department of Medicine, University of Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
| | - Ulf Ziemann
- Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard Karls University, Tübingen, Germany
| | - Walter Paulus
- Department of Clinical Neurophysiology, Georg-August University, Göttingen, Germany
| | - Luis Garcia-Larrea
- Inserm U 1028, NeuroPain Team, Neuroscience Research Center of Lyon (CRNL), Lyon-1 University, Bron, France; Pain Unit, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Bron, France
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Voineskos D, Daskalakis ZJ. A primer on the treatment of schizophrenia through repetitive transcranial magnetic stimulation. Expert Rev Neurother 2014; 13:1079-82. [DOI: 10.1586/14737175.2013.840416] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Aleman A. Use of repetitive transcranial magnetic stimulation for treatment in psychiatry. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE 2013; 11:53-9. [PMID: 24023548 PMCID: PMC3766755 DOI: 10.9758/cpn.2013.11.2.53] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Revised: 04/15/2013] [Accepted: 05/17/2013] [Indexed: 12/24/2022]
Abstract
The potential of noninvasive neurostimulation by repetitive transcranial magnetic stimulation (rTMS) for improving psychiatric disorders has been studied increasingly over the past two decades. This is especially the case for major depression and for auditory-verbal hallucinations in schizophrenia. The present review briefly describes the background of this novel treatment modality and summarizes evidence from clinical trials into the efficacy of rTMS for depression and hallucinations. Evidence for efficacy in depression is stronger than for hallucinations, although a number of studies have reported clinically relevant improvements for hallucinations too. Different stimulation parameters (frequency, duration, location of stimulation) are discussed. There is a paucity of research into other psychiatric disorders, but initial evidence suggests that rTMS may also hold promise for the treatment of negative symptoms in schizophrenia, obsessive compulsive disorder and post-traumatic stress disorder. It can be concluded that rTMS induces alterations in neural networks relevant for psychiatric disorders and that more research is needed to elucidate efficacy and underlying mechanisms of action.
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Affiliation(s)
- André Aleman
- Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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Slotema CW, Aleman A, Daskalakis ZJ, Sommer IE. Meta-analysis of repetitive transcranial magnetic stimulation in the treatment of auditory verbal hallucinations: update and effects after one month. Schizophr Res 2012; 142:40-5. [PMID: 23031191 DOI: 10.1016/j.schres.2012.08.025] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Revised: 08/20/2012] [Accepted: 08/28/2012] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Several meta-analyses considering repetitive transcranial magnetic stimulation (rTMS) for auditory verbal hallucinations (AVH) have been performed with moderate to high mean weighted effect sizes. Since then several negative findings were reported in relatively large samples. The aim of this study was to provide an update of the literature on the efficacy of rTMS for AVH and to investigate the effect of rTMS one month after the end of treatment. DATA SOURCES A literature search was performed from 1966 through August 2012 using Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Embase Psychiatry, Ovid Medline, PsycINFO and PubMed. Randomized, double blind, sham-controlled studies with severity of AVH or severity of psychosis as an outcome measure were included. STUDY SELECTION Data were obtained from 17 randomized studies of rTMS for AVH. Five studies fulfilled the criteria for the meta-analysis on the effect of rTMS one month after the end of treatment. DATA EXTRACTION Standardized mean weighted effect sizes of rTMS versus sham were computed on pre- and posttreatment comparisons. DATA SYNTHESIS The mean weighted effect size of rTMS directed at the left temporoparietal area was 0.44 (95% CI 0.19-0.68). A separate meta-analysis including studies directing rTMS at other brain regions revealed a mean weighted effect size of 0.33 (95% CI 0.17-0.50) in favor of real TMS. The effect of rTMS was no longer significant at one month of follow-up (mean weighted effect size=0.40, 95% CI -0.23-0.102). Side effects were mild and the number of dropouts in the real TMS group was not significantly higher than in the sham group. CONCLUSIONS With the inclusion of studies with larger patient samples, the mean weighted effect size of rTMS directed at the left temporoparietal area for AVH has decreased, although the effect is still significant. The duration of the effect of rTMS may be less than one month. More research is needed in order to optimize parameters and further evaluate the clinical relevance of this intervention.
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Affiliation(s)
- C W Slotema
- Parnassia Bavo Psychiatric Institute, Lijnbaan 4, 2512 VA The Hague, The Netherlands.
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