Efficacy and tolerability of repetitive transcranial magnetic stimulation for late-life depression: A systematic review and meta-analysis.
Journal of affective disorders
BACKGROUND:Repetitive transcranial magnetic stimulation (rTMS) is a widely available treatment for major depression, but its efficacy and tolerability are uncertain for patients with late-life depression (LLD). To assess the existing evidence of rTMS for LLD treatment, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) according to PRISMA guidelines. METHODS:We retrieved RCTs from four databases published between 1 January 2000 and 10 September 2021 comparing the effects of active and sham stimulation in LLD patients. We performed subgroup analyses to examine the impact of different parameters. The primary outcomes were the response and discontinuation rates of rTMS for LLD patients, representing for efficacy and tolerability, respectively. Secondary outcomes were remission and dropout rates. Discontinuation referred to patients who withdrew for any reason, while dropout referred to participants who withdrew early because of adverse events. RESULTS:Nine articles describing 11 studies (two articles each contained two studies) met the eligibility criteria. All outcomes were analyzed using a random-effects model. The summary analysis of nine suitable RCTs revealed a cumulative response rate of 2.86 (95 % confidence interval (95 % CI), 1.87-4.37) and a remission rate of 4.02 (95 % CI, 1.83-8.81) in the active group compared to the sham group. The pooled odds ratios (ORs) for discontinuation and dropout rates were not significantly different between the two groups. In addition, some rTMS parameters were associated with better efficacy. CONCLUSIONS:The meta-analysis suggested that rTMS is an effective, well-tolerated treatment for patients with LLD. Future efforts should enhance study methodologies to improve their efficacy and increase the homogeneity of rTMS parameters to promote comparability between studies.
10.1016/j.jad.2022.11.027
Excess Significance Bias in Repetitive Transcranial Magnetic Stimulation Literature for Neuropsychiatric Disorders.
Amad Ali,Jardri Renaud,Rousseau Chloé,Larochelle Yann,Ioannidis John P A,Naudet Florian
Psychotherapy and psychosomatics
INTRODUCTION:Repetitive transcranial magnetic stimulation (rTMS) has been widely tested and promoted for use in multiple neuropsychiatric conditions, but as for many other medical devices, some gaps may exist in the literature and the evidence base for the clinical efficacy of rTMS remains under debate. OBJECTIVE:We aimed to test for an excess number of statistically significant results in the literature on the therapeutic efficacy of rTMS across a wide range of meta-analyses and to characterize the power of studies included in these meta-analyses. METHODS:Based on power calculations, we computed the expected number of "positive" datasets for a medium effect size (standardized mean difference, SMD = 0.30) and compared it with the number of observed "positive" datasets. Sensitivity analyses considered small (SMD = 0.20), modest (SMD = 0.50), and large (SMD = 0.80) effect sizes. RESULTS:A total of 14 meta-analyses with 228 datasets (110 for neurological disorders and 118 for psychiatric disorders) were assessed. For SMD = 0.3, the number of observed "positive" studies (n = 94) was larger than expected (n = 35). We found evidence for an excess of significant findings overall (p < 0.0001) and in 8/14 meta-analyses. Evidence for an excess of significant findings was also observed for SMD = 0.5 for neurological disorders. Of the 228 datasets, 0 (0%), 0 (0%), 3 (1%), and 53 (23%) had a power >0.80, respectively, for SMDs of 0.30, 0.20, 0.50, and 0.80. CONCLUSION:Most studies in the rTMS literature are underpowered. This results in fragmentation and waste of research efforts. The somewhat high frequency of "positive" results seems spurious and may reflect bias. Caution is warranted in accepting rTMS as an established treatment for neuropsychiatric conditions.
10.1159/000502805
Repetitive transcranial magnetic stimulation for treatment resistant depression: Re-establishing connections.
Anderson Rodney J,Hoy Kate E,Daskalakis Zafiris J,Fitzgerald Paul B
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
Repetitive transcranial magnetic stimulation (rTMS) is a relatively recent addition to the neurostimulation armamentarium for treating individuals suffering from treatment refractory depression and has demonstrated efficacy in clinical trials. One of the proposed mechanisms of action underlying the therapeutic effects of rTMS for depression involves the modulation of depression-associated dysfunctional activity in distributed brain networks involving frontal cortical and subcortical limbic regions, via changes to aberrant functional and structural connectivity. Although there is currently a paucity of published data, we review changes to functional and structural connectivity following rTMS for depression. Current evidence suggests an rTMS-induced normalisation of depression-associated dysfunction within and between large scale functional networks, including the default mode, central executive and salience networks, associated with an amelioration of depressive symptoms. Additionally, changes to measures of white matter microstructure, primarily in the dorsolateral prefrontal cortex, have also been reported following rTMS for depression, possibly reversing depression-associated abnormalities. We argue that measures of functional and structural connectivity can be used to optimise rTMS targeting within the dorsolateral prefrontal cortex and also to explore novel rTMS targets for depression. Finally, we discuss the utility of measures of brain connectivity as predictive biomarkers of rTMS treatment response in guiding therapeutic decisions.
10.1016/j.clinph.2016.08.015
Use of a Double-Cone Coil in Transcranial Magnetic Stimulation for Depression Treatment.
Monteiro Dennison Carreiro,Cantilino Amaury
Neuromodulation : journal of the International Neuromodulation Society
INTRODUCTION:Approximately 15% of all people will experience a depressive episode throughout their lives, and by 2020, depression will be the second largest cause of disability around the world. Transcranial magnetic stimulation (TMS) has been shown to be an effective option for treating this condition. Devices such as the double-cone coil may bring new insights regarding depression treatment. METHODS:A literature search was performed on PubMed, ScienceDirect, Cochrane, LILACS, and Google Scholar by applying the descriptors "depression" AND "transcranial magnetic stimulation" AND "double cone-coil." RESULTS:Six studies were considered eligible (three clinical trials, two case series, and one isolated case report). All of them described treatments with transcranial magnetic stimulation by double-cone coil (DC-TMS) at 10 Hz over the dorsomedial prefrontal cortex, achieving response and remission rates of 40-52.4% and 34.7-47.6%, respectively. Two clinical trials investigated both intermittent theta-burst stimulation and 10 Hz TMS, suggesting a slight advantage of the latter. They also found no additional gains by combining both techniques. CONCLUSION:Despite the small number of controlled clinical trials and the small sample sizes, which limit the generalization of the obtained results, the collected data provide an optimistic perspective on the effectiveness of using DC-TMS for depression treatment.
10.1111/ner.12896
Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief?
Wiley interdisciplinary reviews. Cognitive science
Transcranial magnetic stimulation (TMS) is a safe, tolerable, and evidence-based intervention for major depressive disorder (MDD). However, even after decades of research, nearly half of the patients with MDD fail to respond to conventional TMS, with responding slowly and requiring daily attendance at the treatment site for 4-6 weeks. To intensify antidepressant efficacy and shorten treatment duration, accelerated TMS protocols, which involve multiple sessions per day over a few days, have been proposed and evaluated for safety and viability. We reviewed and summarized the current knowledge in accelerated TMS, including stimulation parameters, antidepressant efficacy, anti-suicidal efficacy, safety, and adverse effects. Limitations and suggestions for future directions are also addressed, along with a brief discussion on the application of accelerated TMS during the COVID-19 pandemic. This article is categorized under: Neuroscience > Clinical Neuroscience.
10.1002/wcs.1666
Efficacy and safety of transcranial magnetic stimulation for treating major depressive disorder: An umbrella review and re-analysis of published meta-analyses of randomised controlled trials.
Clinical psychology review
OBJECTIVES:We re-analysed data from published meta-analyses testing the effects of Transcranial Magnetic Stimulation (TMS) on Major Depressive Disorder (MDD) in adults. We applied up-to-date meta-analytic techniques for handling heterogeneity including the random-effects Hartung-Knapp-Sidik-Jonkman method and estimated 95% prediction intervals. Heterogeneity practices in published meta-analyses were assessed as a secondary aim. STUDY DESIGN AND SETTING:We performed systematic searches of systematic reviews with meta-analyses that included randomised controlled trials assessing the efficacy, tolerability, and side effects of TMS on MDD. We performed risk of bias assessment using A MeaSurement Tool to Assess Reviews (AMSTAR) 2 and re-analysed meta-analyses involving 10 or more primary studies. RESULTS:We included 29 systematic reviews and re-analysed 15 meta-analyses. Authors of all meta-analyses interpreted findings to suggest TMS is safe and effective for MDD. Our re-analysis showed that in 14 out of 15 meta-analyses, the 95% prediction intervals included the null and captured values in the opposite effect direction. We also detected presence of small-study effects in some meta-analyses and 24 out of 25 systematic reviews received an AMSTAR 2 rating classed as critically low. CONCLUSION:Authors of all included meta-analyses interpreted findings to suggest TMS is safe and effective for MDD despite lack of comprehensive investigation of heterogeneity. Our re-analysis revealed the direction and magnitude of treatment effects vary widely across different settings. We also found high risk of bias in the majority of included systematic reviews and presence of small-study effects in some meta-analyses. Because of these reasons, we argue TMS for MDD may not be as effective and potentially less tolerated in some populations than current evidence suggests.
10.1016/j.cpr.2022.102236
Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions.
Baeken Chris,Brem Anna-Katharine,Arns Martijn,Brunoni Andre R,Filipčić Igor,Ganho-Ávila Ana,Langguth Berthold,Padberg Frank,Poulet Emmanuel,Rachid Fady,Sack Alexander T,Vanderhasselt Marie-Anne,Bennabi Djamila
Current opinion in psychiatry
PURPOSE OF REVIEW:After three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS), major depressive disorder (MDD) has proven to be the primary field of application. MDD poses a major challenge for health systems worldwide, emphasizing the need for improving clinical efficacy of existing rTMS applications and promoting the development of novel evidence-based rTMS treatment approaches. RECENT FINDINGS:Several promising new avenues have been proposed: novel stimulation patterns, targets, and coils; combinatory treatments and maintenance; and personalization and stratification of rTMS parameters, and treatment of subpopulations. SUMMARY:This opinion review summarizes current knowledge in the field and addresses the future direction of rTMS treatment in MDD, facilitating the establishment of this clinical intervention method as a standard treatment option and continuing to improve response and remission rates, and take the necessary steps to personalize rTMS-based treatment approaches.
10.1097/YCO.0000000000000533
Transcranial magnetic stimulation for post-operative neurorehabilitation in neuro-oncology: a review of the literature and future directions.
Journal of neuro-oncology
INTRODUCTION:Transcranial magnetic stimulation (TMS) is a neuromodulation technology capable of targeted stimulation and inhibition of cortical areas. Repetitive TMS (rTMS) has demonstrated efficacy in the treatment of several neuropsychiatric disorders, and novel uses of rTMS for neurorehabilitation in patients with acute and chronic neurologic deficits are being investigated. However, studies to date have primarily focused on neurorehabilitation in stroke patients, with little data supporting its use for neurorehabilitation in brain tumor patients. METHODS:We performed a review of the current available literature regarding uses of rTMS for neurorehabilitation in post-operative neuro-oncologic patients. RESULTS:Data have demonstrated that rTMS is safe in the post-operative neuro-oncologic patient population, with minimal adverse effects and no documented seizures. The current evidence also demonstrates potential effectiveness in terms of neurorehabilitation of motor and language deficits. CONCLUSIONS:Although data are overall limited, both safety and effectiveness have been demonstrated for the use of rTMS for neurorehabilitation in the neuro-oncologic population. More randomized controlled trials and specific comparisons of contralateral versus ipsilateral rTMS protocols should be explored. Further work may also focus on individualized, patient-specific TMS treatment protocols for optimal functional recovery.
10.1007/s11060-022-03987-9
Transcranial magnetic stimulation in the treatment of adolescent depression: a systematic review and meta-analysis of aggregated and individual-patient data from uncontrolled studies.
European child & adolescent psychiatry
Transcranial magnetic stimulation (TMS) is a non-invasive treatment for adolescent major depressive disorder (MDD). Existing evidence on the efficacy of TMS in adolescent MDD awaits quantitative synthesis. A systematic literature search was conducted, and data from eligible studies were synthesized using random-effects models. Treatment-covariate interactions were examined in exploratory analyses of individual-patient data (IPD). Systematic search of the literature yielded 1264 hits, of which 10 individual studies (2 randomized trials) were included for quantitative synthesis of mainly uncontrolled studies. Individual patient data (IPD) were available from five trials (all uncontrolled studies). Quantitative synthesis of aggregated data revealed a statistically significant negative overall standardized mean change (pooled SMCC = 2.04, 95% CI [1.46; 2.61], SE = 0.29, p < .001), as well as a significant overall treatment response rate (Transformed Proportion = 41.30%, 95% CI [31.03; 51.57], SE = 0.05; p < 0.001), considering data from baseline to post-treatment. Exploratory IPD analyses suggests TMS might be more effective in younger individuals and individuals with more severe depression, and efficacy might be enhanced with certain treatment modality settings, including higher number of TMS sessions, longer treatment durations, and unilateral and not bilateral stimulation. Existing studies exhibit methodological shortcomings, including small-study effects and lack of control group, blinding, and randomization-compromising the credibility of the present results. To date, two randomized controlled trials on TMS in adolescent depression have been published, and the only large-scale randomized trial suggests TMS is not more effective than sham stimulation. Future large-scale, randomized, and sham-controlled trials are warranted. Future trials should ensure appropriate selection of patients for TMS treatment and guide precision medicine approaches for stimulation protocols.
10.1007/s00787-022-02021-7
Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.
Neuropsychology review
To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges' g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges' g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.
10.1007/s11065-022-09564-1
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.
O'Reardon John P,Solvason H Brent,Janicak Philip G,Sampson Shirlene,Isenberg Keith E,Nahas Ziad,McDonald William M,Avery David,Fitzgerald Paul B,Loo Colleen,Demitrack Mark A,George Mark S,Sackeim Harold A
Biological psychiatry
BACKGROUND:We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS:In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS:Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS:Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.
10.1016/j.biopsych.2007.01.018
A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee.
Groppa S,Oliviero A,Eisen A,Quartarone A,Cohen L G,Mall V,Kaelin-Lang A,Mima T,Rossi S,Thickbroom G W,Rossini P M,Ziemann U,Valls-Solé J,Siebner H R
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.
10.1016/j.clinph.2012.01.010
Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression.
McClintock Shawn M,Reti Irving M,Carpenter Linda L,McDonald William M,Dubin Marc,Taylor Stephan F,Cook Ian A,O'Reardon John,Husain Mustafa M,Wall Christopher,Krystal Andrew D,Sampson Shirlene M,Morales Oscar,Nelson Brent G,Latoussakis Vassilios,George Mark S,Lisanby Sarah H, ,
The Journal of clinical psychiatry
OBJECTIVE:To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). PARTICIPANTS:Participants included a group of 17 expert clinicians and researchers with expertise in the clinical application of rTMS, representing both the National Network of Depression Centers (NNDC) rTMS Task Group and the American Psychiatric Association Council on Research (APA CoR) Task Force on Novel Biomarkers and Treatments. EVIDENCE:The consensus statement is based on a review of extensive literature from 2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990 through 2016. The search terms included variants of major depressive disorder and transcranial magnetic stimulation. The results were limited to articles written in English that focused on adult populations. Of the approximately 1,500 retrieved studies, a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice settings. CONSENSUS PROCESS:In cases in which the research evidence was equivocal or unclear, a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as "expert opinion." CONCLUSIONS:Multiple randomized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy. These consensus recommendations, developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments, provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD.
10.4088/JCP.16cs10905
Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018).
Lefaucheur Jean-Pascal,Aleman André,Baeken Chris,Benninger David H,Brunelin Jérôme,Di Lazzaro Vincenzo,Filipović Saša R,Grefkes Christian,Hasan Alkomiet,Hummel Friedhelm C,Jääskeläinen Satu K,Langguth Berthold,Leocani Letizia,Londero Alain,Nardone Raffaele,Nguyen Jean-Paul,Nyffeler Thomas,Oliveira-Maia Albino J,Oliviero Antonio,Padberg Frank,Palm Ulrich,Paulus Walter,Poulet Emmanuel,Quartarone Angelo,Rachid Fady,Rektorová Irena,Rossi Simone,Sahlsten Hanna,Schecklmann Martin,Szekely David,Ziemann Ulf
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.
10.1016/j.clinph.2019.11.002
Transcranial magnetic stimulation: a primer.
Hallett Mark
Neuron
Transcranial magnetic stimulation (TMS) is a technique for noninvasive stimulation of the human brain. Stimulation is produced by generating a brief, high-intensity magnetic field by passing a brief electric current through a magnetic coil. The field can excite or inhibit a small area of brain below the coil. All parts of the brain just beneath the skull can be influenced, but most studies have been of the motor cortex where a focal muscle twitch can be produced, called the motor-evoked potential. The technique can be used to map brain function and explore the excitability of different regions. Brief interference has allowed mapping of many sensory, motor, and cognitive functions. TMS has some clinical utility, and, because it can influence brain function if delivered repetitively, it is being developed for various therapeutic purposes.
10.1016/j.neuron.2007.06.026
Transcranial magnetic stimulation: Neurophysiological and clinical applications.
Burke Matthew J,Fried Peter J,Pascual-Leone Alvaro
Handbook of clinical neurology
Transcranial magnetic stimulation (TMS) is a safe and noninvasive means of electrically stimulating the brain by electromagnetic induction. TMS is capable of probing intracortical circuits and modulating cortical activity in humans; as such it has been instrumental to studying the neurophysiology and functional neuroanatomy of the frontal lobes. For example, using TMS to induce "virtual lesions"-transient disruption of function in the targeted brain region-has yielded important insights into the functional organization of the prefrontal cortex (PFC) with respect to working memory, language, and other core cognitive functions. Whereas neuroimaging is typically limited to observing correlations between brain function and behavior, TMS, by interacting with neural circuits, can lead to causal inferences that bridge human, nonhuman primate, and other model system studies. Applied repetitively in trains of stimuli, TMS is also capable of normalizing aberrant patterns of cortical activity in the treatment of neurologic and psychiatric disorders. The earliest and most well-established clinical use of repetitive TMS is in the treatment of medication-resistant depression with high-frequency stimulation of the left dorsolateral PFC. Research efforts to identify other promising clinical applications-such as for stroke and Alzheimer's disease-are rapidly expanding; however, the majority of these indications have yet to have devices cleared by the FDA for on-label use.
10.1016/B978-0-12-804281-6.00005-7
Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.
10.1016/j.clinph.2009.08.016