References

GENERAL INFORMATION

Groundbreaking Study Demonstrates Advantages of BrainsWay Deep TMS in Treating Major Depressive Disorder

BrainsWay Ltd. (NASDAQ: BWAY, TASE: BWAY), a global leader in the advanced non-invasive treatment of brain disorders, today announced the publication of a third-party study which demonstrated that Deep Transcranial Magnetic Stimulation (dTMS) plus standard medication was significantly more effective at reducing depression levels among Major Depressive Disorder (MDD) patients compared with standard medication alone.

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6 Things Everyone Should Know About OCD

People get rough ideas about mental illness from movies or TV shows, and popular culture often simplifies or even completely misrepresents what it is really like to live with mental illness. Obsessive-compulsive disorder (OCD) is no different. Many people associate their knowledge and understanding of OCD with popular TV shows, like The Big Bang Theory and Monk. Consequently, OCD may be one of the most misunderstood mental health conditions.

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3000 Pulses Later By Martha Rhodes -Pushpin Press 2013 (ISBN-13: 978-0985533922)

A new book released today chronicles one woman’s 30-year battle with major depression and sheds light on how a novel, non-drug therapy saved her life. 3,000 Pulses intimately documents 62-year-old Martha Rhodes’ nearly lifelong journey with depression and gives a harrowing yet inspirational account of how it is possible to reclaim your life from the powerful grip of mental illness and attempted suicide.

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ACADEMIC REFERENCES

DEPRESSION

Comparison between neurostimulation techniques repetitive transcranial magnetic stimulation vs electroconvulsive therapy for the treatment of resistant depression: patient preference and cost-effectiveness. Patient Prefer Adherence. 2016;10:1481-1487.

Major depressive disorder (MDD) is a common disorder, widely distributed in the population, and is often associated with severe symptoms and functional impairment. It has been estimated that 30% of MDD patients do not benefit adequately from therapeutic interventions, including pharmacotherapy and psychotherapy. Treatment-resistant depression (TRD) is generally defined as a failure to achieve remission, despite therapeutic interventions.

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Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression. Brain Stimulation 8 (2015) 787-794

Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events.

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Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Major Depression: A prospective multicenter randomized controlled trial

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group, resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%; remission: 32.6 vs. 14.6%). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.

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A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period

Transcranial magnetic stimulation (TMS) is an effective and safe acute treatment for patients not benefiting from antidepressant pharmacotherapy. Few studies have examined its longer term durability. This study assessed the long-term effectiveness of TMS in naturalistic clinical practice settings following acute treatment. Adult patients with a primary diagnosis of unipolar, nonpsychotic major depressive disorder (DSM-IV clinical criteria), who did not benefit from antidepressant medication, received TMS treatment in 42 clinical practices. Two hundred fifty-seven patients completed a course of acute TMS treatment and consented to follow-up over 52 weeks. Assessments were obtained at 3, 6, 9, and 12 months. The study was conducted between March 2010 and August 2012. Compared with pre-TMS baseline, there was a statistically significant reduction in mean total scores on the Clinical Global Impressions-Severity of Illness scale (primary outcome), 9-Item Patient Health Questionnaire, and Inventory of Depressive Symptoms-Self Report (IDS-SR) at the end of acute treatment (all P < .0001), which was sustained throughout follow-up (all P < .0001). The proportion of patients who achieved remission at the conclusion of acute treatment remained similar at conclusion of the long-term follow-up. Among 120 patients who met IDS-SR response or remission criteria at the end of acute treatment, 75 (62.5%) continued to meet response criteria throughout long-term follow-up. After the first month, when the majority of acute TMS tapering was completed, 93 patients (36.2%) received reintroduction of TMS. In this group, the mean (SD) number of TMS treatment days was 16.2. TMS demonstrates a statistically and clinically meaningful durability of acute benefit over 12 months of follow-up. This was observed under a pragmatic regimen of continuation antidepressant medication and access to TMS retreatment for symptom recurrence.

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Improvement in quality of life with left prefrontal transcranial magnetic stimulation in patients with pharmacoresistant major depression: acute and six month outcomes. Brain Stimul. 2014 Mar-Apr; 7(2):219-25.

Transcranial magnetic stimulation (TMS) is a safe and effective treatment for major depression. We describe quality of life (QOL) outcomes from acute treatment with TMS, and describe the durability of benefit across 24-weeks.

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George, M.S. (2010) Transcranial Magnetic Stimulation for the Treatment of Depression. Expert Rev. Neurother. 10(11), 1761–1772

Repeated daily left prefrontal transcranial magnetic stimulation (TMS) was first proposed as a potential treatment for depression in 1993. Multiple studies from researchers around the world since then have repeatedly demonstrated that TMS has antidepressant effects greater than sham treatment, and that these effects are clinically meaningful. A large industry-sponsored trial, published in 2007, resulted in US FDA approval in October 2008. Most recently, a large NIH-sponsored trial, with a more rigorous sham technique, found that a course of treatment (3–5 weeks) was statistically and clinically significant in reducing depression. However, consistently showing statistically and clinically significant antidepressant effects, and gaining regulatory approval, is merely the beginning for this new treatment. As with any new treatment involving a radically different approach, there are many unanswered questions about TMS, and the field is still rapidly evolving. These unanswered questions include the appropriate scalp location, understanding the mechanisms of action, refining the ‘dose’ (frequency, train, number of stimuli/day and pattern of delivery), understanding whether and how TMS can be combined with medications or talking/exposure therapy, or both, and how to deliver maintenance TMS. This article summarizes the available clinical information, and discusses key areas where more research is needed. TMS reflects a paradigm shift in treating depression. It is a safe, relatively noninvasive, focal brain stimulation treatment that does not involve seizures or implanted wires, and does not have drug–drug interactions or systemic side effects.

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Repetitive Transcranial Magnetic Stimulation For Depressive Disorders By Paul B. Fitzgerald and Z. Jeff Daskalakis -Springer 2013 (ISBN-13: 978-3642364662)

​Repetitive transcranial magnetic stimulation (rTMS) treatment is increasingly being used in the management of patients with depression. Nevertheless, considerable ignorance still exists about the treatment in general psychiatric practice. This concise clinical guide will serve as a reference and practical tool for clinicians working with or learning about this treatment technique. The opening chapters provide basic information on the history and development of rTMS treatment and its mechanism of action. Use of the treatment in depression is then addressed in detail, with explanation of the evidence base and discussion of a variety of clinical issues. Side-effects of treatment are explored, and careful consideration is given to the establishment of rTMS treatment programs and the training of clinicians. The final chapters will provide a brief overview of potential rTMS applications in other psychiatric conditions and some background on related treatments.

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The relationship between brain oscillatory activity and therapeutic effectiveness of transcranial magnetic stimulation in the treatment of major depressive disorder. Frontiers in Human Neuroscience. February 2013 Volume 7 Article 37

Major depressive disorder (MDD) is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive transcranial magnetic stimulation (rTMS) is a robust treatment for MDD, but the mechanism of action (MOA) of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this MOA and achieve better antidepressant effectiveness. We propose that rTMS can be administered: (1) synchronized to a patient’s individual alpha frequency (IAF), or synchronized rTMS (sTMS); (2) as a low magnetic field strength sinusoidal waveform; and, (3) broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

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Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice

Few studies have examined the effectiveness of transcranial magnetic stimulation (TMS) in real-world clinical practice settings. Forty-two US-based clinical TMS practice sites treated 307 outpatients with Major Depressive Disorder (MDD), and persistent symptoms despite antidepressant pharmacotherapy. Treatment was based on the labeled procedures of the approved TMS device. Assessments were performed at baseline, week 2, at the point of maximal acute benefit, and at week 6 when the acute course extended beyond 6 weeks. The primary outcome was change in the Clinician Global Impressions-Severity of Illness from baseline to end of acute phase. Secondary outcomes were change in continuous and categorical outcomes on self-report depression scales (9-Item Patient Health Questionnaire [PHQ-9], and Inventory of Depressive Symptoms-Self Report [IDS-SR]). Patients had a mean ± SD age of 48.6 ± 14.2 years and 66.8% were female. Patients received an average of 2.5 (± 2.4) antidepressant treatments of adequate dose and duration without satisfactory improvement in this episode. There was a significant change in CGI-S from baseline to end of treatment (-1.9 ± 1.4, P < .0001). Clinician-assessed response rate (CGI-S) was 58.0% and remission rate was 37.1%. Patient-reported response rate ranged from 56.4 to 41.5% and remission rate ranged from 28.7 to 26.5%, (PHQ-9 and IDS-SR, respectively). Outcomes demonstrated response and adherence rates similar to research populations. These data indicate that TMS is an effective treatment for those unable to benefit from initial antidepressant medication.

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Long-Term Efficacy of Repeated Daily Prefrontal Transcranial Magnetic Stimulation (TMS) in Treatment-Resistant Depression. Depress Anxiety. 2012 October ; 29(10): 883–890

A few studies have examined the durability of transcranial magnetic stimulation (TMS) antidepressant benefit once patients remitted. This study examined the long-term durability of clinical benefit from TMS using a protocol-specified TMS taper and either continuation pharmacotherapy or naturalistic follow-up.

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Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry. 2012; 73: e567–73

Transcranial magnetic stimulation (TMS) is a US Food and Drug Administration–approved treatment for major depressive disorder (MDD) in patients who have not responded to 1 adequate antidepressant trial in the current episode. In a retrospective cohort study, we examined the effectiveness and safety of TMS in the first 100 consecutive patients treated for depression (full DSM-IV criteria for major depressive episode in either major depressive disorder or bipolar disorder) at an academic medical center between July 21, 2008, and March 25, 2011.

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H-Coil Repetitive Transcranial Magnetic Stimulation for Treatment Resistant Major Depressive Disorder

Evidence has shown that repetitive transcranial magnetic stimulation (rTMS) can be effective as an acute treatment for major depressive disorder (MDD). However, few studies have examined the safety and feasibility of rTMS as a long-term\continuation treatment. Deep-TMS is a novel tool enabling deeper stimulation than standard coils. The current study examined the safety and feasibility of repetitive deep-TMS continuation treatment for MDD over the course of 18 weeks, following 4 weeks of acute treatment. A total of 29 MDD patients were enrolled in the study. rTMS sessions (20 Hz) were given for a total of 22 weeks, divided into: 4 weeks of acute daily treatments, followed by 18 weeks of continuation treatments. Clinical evaluations were performed weekly throughout the study. A significant decrease from baseline in Hamilton Depression Rating Scale (HDRS) score was found at the end of the acute phase, and maintained throughout the study ( P < 0.0001). The Kaplan – Meier estimated probability of response was 46.15% (SE = 9.78%) at the end of the acute phase, and 81.12% (SE = 9.32%) at the end of the study (22 weeks). Probability of remission at the end of the acute phase was 26.92% (SE = 8.70%) and 71.45% (SE = 10.99%) at the end of the study. Response in the acute phase was indicative of response in the continuation phases. The procedure was generally well tolerated and no adverse events were reported. The results suggest that H-coil deep-TMS administered continuation treatment can help maintain an antidepressant effect for 18 weeks, following 4 weeks of acute treatment.

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Transcranial Magnetic Stimulation for Major Depressive Disorder: A Pragmatic Approach to Implementing TMS in a Clinical Practice. Ann Clin Psychiatry. 2010 Nov;22(4 Suppl):S4-11.

Another option for managing major depressive disorder (MDD) became available in October 2008 with the Food and Drug Administration’s (FDA) market clearance of NeuroStar TMS (transcranial magnetic stimulation) Therapy System. A panel of psychiatrists who have been treating patients with NeuroStar TMS Therapy in their clinics assembled for a virtual roundtable discussion regarding their experiences. In this supplement, the panel addresses the following issues: the FDA-cleared indication for use of NeuroStar TMS Therapy; logistic and staffing considerations in the outpatient setting; selecting the right patient for TMS Therapy; talking with patients and family about TMS Therapy. To give the overview a meaningful context, each panelist shares a personal account of a patient case, describing the treatment course and outcomes achieved with TMS Therapy.

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Accelerated Repetitive Transcranial Magnetic Stimulation for Treatment Resistant Depression. Depression and Anxiety 27:960-963

Repetitive transcranial magnetic stimulation (rTMS) has shown safety and efficacy for treatment-resistant depression, but requires daily treatment for 4-6 weeks. Accelerated TMS, with all treatments delivered over a few days, would have significant advantages in terms of access and patient acceptance.

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Demitrack, M.A. (2010) Transcranial Magnetic Stimulation for the Treatment of Major Depression clinical. Economic, and Practical Issues: Part II Psychopharm Review, Vol. 45, No. 8 August 2010

Part I of this two-part series (vol. 45, no. 4) discussed the clinical and economic burder of major depression; the compounding issue of treatment resistance; and cost analyses comparing transcranial magnetic stimulation (TMS) with standard clinical care (e.g., complex pharmacotherapy, electrconvulsive therapy [ECT]) for treatment resistance depression (TRD). Part II reviews practical issues in the clinical use of TMS, which have merged since its approval by the FDA for this indication.

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Demitrack, M.A. (2010) Transcranial Magnetic Stimulation for the Treatment of Major Depression clinical. Economic, and Practical Issues: Part I Psychopharm Review, Vol. 45, No. 4 April 2010

This article is the first of two parts. Part I describes pervasive problems of major depression, the issue of treatment resistance and its economic impact. The article is intended to enable the reader to evaluate the epidemiology, functional health consequences, and economic burder of major depression, especially in its treatment-resistant form.

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Transcranial Magnetic Stimulation in the Acute Treatment of Major Depressive Disorder: Clinical Response in an Open-Label Extension Trial. J Clin Psychiatry 69:3, March 2008

This report describes the results of an open-label extension study of active trans-cranial magnetic stimulation (TMS) in medication-resistant patients with major depressive disorder who did not benefit from an initial course of therapy in a previously reported 6-week, randomized controlled study of active versus sham TMS.

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OCD

Efficacy & Safety of Deep TMS for OCD: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial

Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study.

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PTSD

Karsen, E.F., Watts, B.V., Holtzheimer, P.E. (2014) Review of the Effectiveness of Transcranial Magnetic Stimulation for Post-traumatic Stress Disorder. Brain Stimulation 7 (2014) 151-157

Post-traumatic stress disorder (PTSD) is a psychiatric condition with significant morbidity and limited treatment options. Transcranial magnetic stimulation (TMS) has been shown to be an effective treatment for mental illnesses including major depressive disorder.

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OTHER APPLICATIONS OF TMS

Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer’s disease patients

Repetitive transcranial magnetic stimulation (rTMS) acts as a kind of widely-applied and non-invasive method in the intervention of some neurological disorders. This prospective, randomized, double-blind, placebo-controlled trial investigates the effect of rTMS on 30 cases of Alzheimer’s disease (AD) participants, who were classified into mild and moderate groups. Neuropsychological tests were carried out using the AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) before, immediately after, and 6 weeks after the intervention. In this work, data from 30 AD patients revealed that there was no obvious interaction effect of time-by-group. The ADAS-cog, MMSE and WHO-UCLA AVLT score in the rTMS group was significantly improved compared with baselines at 6 weeks after treatment (all p<0.05). Meanwhile, MoCA scores were also obviously ameliorated in the mild AD patients with rTMS. Besides, subgroup analysis showed that the effect of rTMS on the memory and language of mild AD patients was superior to those of moderate AD patients. In conclusion, our findings suggested that repetitive transcranial magnetic stimulation improves cognitive function, memory and language level of AD patients, especially in the mild stage of AD. Thus, rTMS can be recommended as a promising adjuvant therapy combined with cholinesterase inhibitors at the mild stage of AD patients.

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Targeting Withdrawal Symptoms in Men Addicted to Methamphetamine With Transcranial Magnetic Stimulation

Drug withdrawal is associated with aversive experiences, which promotes relapse.1 Different neurotransmitters, neuropeptides, signal transduction pathways, and brain regions (especially the nucleus accumbens) have been implicated in the occurrence of withdrawal syndrome during abstinence from addictive drugs.2 Withdrawal from methamphetamine results in fatigue, irritability, disturbed sleep, exhaustion, and symptoms of depression and anxiety, which might last for months. Currently, limited pharmaceutical tools are available for detoxification from methamphetamine; vitamins, antidepressants, and antipsychotics have been used to ameliorate withdrawal symptoms in clinical practices.3

In an animal study, optogenetic stimulation of the thalamic-accumbens dopamine D2 medium spiny neuron pathway alleviated somatic signs induced by opiate withdrawal.4 However, it is unknown if noninvasive brain stimulation could facilitate detoxification during the withdrawal period in humans. In this study, we used repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsal-lateral prefrontal cortex (DLPFC) to modulate symptoms of withdrawal from methamphetamine.

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Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research

Autism Spectrum Disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by impairments in social communication, by the presence of restricted and repetitive behaviors, interests and activities, and by abnormalities in sensory reactivity. Transcranial magnetic stimulation (TMS) is a promising, emerging tool for the study and potential treatment of ASD. Recent studies suggest that TMS measures provide rapid and noninvasive pathophysiological ASD biomarkers. Furthermore, repetitive TMS (rTMS) may represent a novel treatment strategy for reducing some of the core and associated ASD symptoms. However, the available literature on the TMS use in ASD is preliminary, composed of studies with methodological limitations. Thus, off-label clinical rTMS use for therapeutic interventions in ASD without an investigational device exemption and outside of an IRB approved research trial is premature pending further, adequately powered and controlled trials. Leaders in this field have gathered annually for a two-day conference (prior to the 2014 and 2015 International Meeting for Autism Research, IMFAR) to share recent progress, promote collaboration across laboratories, and establish consensus on protocols. Here we review the literature in the use of TMS in ASD in the context of the unique challenges required for the study and exploration of treatment strategies in this population. We also suggest future directions for this field of investigations. While its true potential in ASD has yet to be delineated, TMS represents an innovative research tool and a novel, possibly transformative approach to the treatment of neurodevelopmental disorders.

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TMS GUIDELINES & CONSENSUS RECOMMENDATIONS

The Clinical TMS Society Consensus Review and Treatment: Recommendations for TMS Therapy for Major Depressive Disorder

Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4–6 weeks (20–30 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. In 2011, leading TMS clinical providers and researchers created the Clinical TMS Society (cTMSs) (www.clinicaltmssociety.org, Greenwich, CT, USA), incorporated in 2013.

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Taylor JJ, Williams NR, George MS. Beyond Neural Cubism: Promoting a Multidimensional View of Brain Disorders by Enhancing the Integration of Neurology and Psychiatry in Education. Acad Med. 2015 May ; 90(5): 581–586

Cubism was an influential early-20th-century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stemmed from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood, or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders.

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Williams NR, Taylor JJ, Kerns S, Short EB, Kantor EM, George MS. Interventional Psychiatry: Why Now? J Clin Psychiatry. 2014 August ; 75(8): 895–897

Interventional psychiatry offers substantial therapeutic benefits in some neuropsychiatric disorders and enormous potential in treating others. However, as interventional diagnostics and therapeutics require specialized knowledge and skill foreign to many psychiatrists, the emerging subspecialty of interventional psychiatry must be more formally integrated into the continuum of psychiatric training to ensure both safe application and continued growth. By establishing training paradigms for interventional psychiatry, academic medical centers can help fill this knowledge gap. The cultivation of a properly trained cohort of interventional psychiatrists will better meet the challenges of treatment-resistant psychiatric illness through safe and ethical practice, while facilitating a more informed development and integration of novel neuromodulation techniques.

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A Clinical Guide To Transcranial Magnetic Stimulation Edited by Paul E. Holtzheimer and William McDonald -Oxford University Press 2014 (ISBN-13: 978-0199926480)

This resource serves as a reference tool for clinicians in the administration of transcranial magnetic stimulation (TMS) for neuropsychiatric disorders, and it focuses on the clinical applications of TMS and offers detailed information on the safe and effective administration of TMS with consideration of the neurophysiological effects particularly in relation to safety, targeting specific cortical areas and practical issues such as the length of treatment sessions and the durability of the TMS response. It also covers the evidenced based literature and utilizes this literature to inform specific recommendations on the use of rTMS in a clinical setting, while also addressing the efficacy and safety of TMS for neuropsychiatric disorders, including its use in special populations, such as the elderly. Finally, it outlines setting up a TMS service and includes practical issues such as considerations for the qualifications of the person administering the treatment, the use of concomitant medications, what equipment is necessary to have in the treatment room, and monitoring the outcomes to treatment.

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Beam, W., Borckardt, J.J., Reeves, S.T., George, M.S. (2009) An Efficient and Accurate New method for locating the F3 position for prefrontal TMS applications”

The International 10-20 system is a method for standardized placement of electroencephalogram (EEG) electrodes. The 10-20 system correlates external skull locations with the underlying cortical areas. This system accounts for variability in patient skull size by using certain percentages of the circumference and distances between four basic anatomical landmarks. This 10-20 system has recently been used in transcranial magnetic stimulation (TMS) research for locating specific cortical areas. In the treatment of depression (and some types of pain), the desired placement of the TMS coil is often above the left dorsalateral prefrontal cortex (DLPFC) which corresponds to the F3 location given by the 10-20 system. However, for an administrator with little experience with the 10-20 system, the numerous measurements and calculations can be excessively time-consuming. Additionally, with more measurements comes more opportunity for human error. For this reason we have developed a new, simpler and faster way to find the F3 position using only three skull measurements. In this paper, we describe and illustrate the application of the new F3 location system, provide the formulas used in the calculation of the F3 position, and summarize data from 10 healthy adults. After using both the International 10-20 system and this new method, it appears that the new method is sufficiently accurate; however, future investigations may be warranted to conduct more in dept analyses of the method’s utility and potential limitations. This system requires less time and training to find the optimal position for prefrontal coil placement and it saves considerable time compared to the 10-20 EEG system.

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Paulus W, Classen J, Cohen LG, Large CH, Di Lazzaro V, Nitsche M, Pascual-Leone A, Rosenow F, Rothwell JC, Ziemann U. (2008) State of the Art: Pharmacologic Effects on Cortical Excitability Measures Tested by Transcranial Magnetic Stimulation. Brain Stimulation (2008) 1, 151–63

The combination of brain stimulation techniques like transcranial magnetic stimulation (TMS) with CNS active drugs in humans now offers a unique opportunity to explore the physiologic effects of these substances in vivo in the human brain. Motor threshold, motor evoked potential size, motor evoked potential intensity curves, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, short-interval intracortical facilitation, long-interval intracortical inhibition and short latency afferent inhibition represent the repertoire for investigating drug effects on motor cortical excitability by TMS. Here we present an updated overview on the pharmacophysiologic mechanisms with special emphasis on methodologic pitfalls and possible future developments or requirements.

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The Oxford Handbook Of Transcranial Magnetic Simulation Edited by Eric Wassermann, Charles Epstein, and Ulf Ziemann -Oxford University Press 2008 (ISBN-13: 978-0198568926)

Since becoming commercially available in 1985, transcranial magnetic stimulation (TMS) has emerged as an important tool in several areas of neuroscience. Originally envisioned as a way to measure the responsiveness and conduction speed of neurons and synapses in the brain and spinal cord, TMS has also become an important tool for changing the activity of brain neurons and the functions they subserve and an important adjunct to brain imaging and mapping techniques. Along with transcranial electrical stimulation techniques, TMS has diffused far beyond the borders of clinical neurophysiology and into cognitive, perceptual, behavioural, and therapeutic investigation and attracted a highly diverse group of users and would-be users. The Oxford Handbook of Transcranial Stimulation provides an authoritative review of the scientific and technical background required to understand transcranial stimulation techniques and a wide-ranging survey of their burgeoning application in neurophysiology, perception, cognition, emotion, and clinical practice.

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Transcranial Magnetic Stimulation In Clinical Psychiatry Edited by Mark S. George and Robert H. Belmaker -American Psychiatric Publishing 2007 (ISBN-13: 978-1585621972)

As understanding evolves about how different brain regions are involved in carrying out everyday tasks—and in causing brain diseases when they go awry—this book describes a new technology that allows physicians to focally stimulate the brain in awake adults through a non-invasive procedure. Transcranial Magnetic Stimulation in Clinical Psychiatry is an accessible and authoritative review of TMS, a procedure that is showing promise as a treatment in several disorders. Its authors explain how the procedure works, then the latest findings in a wide range of situations—notably in depression, but also in other conditions ranging from migraine to stroke recovery.

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George, M.S., Nahas, Z., Kozel, F.A., Li, X., Denslow, S., Yamanaka, K., Mishory, A., Foust, M.J., Bohning, D.E. (2002) Mechanisms and State of the Art of Transcranial Magnetic Stimulation The Journal of ECT 18(4):170–181

In 1985, Barker et al. built a transcranial magnetic stimulation (TMS) device with enough power to stimulate dorsal roots in the spine. They quickly realized that this machine could likely also noninvasively stimulate the superficial cortex in humans. They waited a while before using their device over a human head, fearing that the TMS pulse might magnetically “erase the hard-drive” of the human brain. Almost 10 years later, in 1994, an editorial in this journal concerned whether TMS might evolve into a potential antidepressant treatment. In the intervening years, there has been an explosion of basic and clinical research with and about TMS. Studies are now uncovering the mechanisms by which TMS affects the brain. It does not “erase the hard-drive” of the brain, and it has many demonstrated research and clinical uses. This article reviews the major recent advances with this interesting noninvasive technique for stimulating the brain, critically reviewing the data on whether TMS has anticonvulsant effects or modulates cortical-limbic loops.

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Insurance Coverage for TMS

Within California, Oregon, and Alaska, Transcranial Magnetic Stimulation has been approved for use with treatment resistant depression by several insurance providers. Insurances that we’re in network with include Cigna, Anthem Blue Cross, Magellan, Tricare, Blue Shield of CA, Blue Shield Federal Employee, Optum, Aetna, MHN, Healthnet, Beacon, Prime Health Services, Provider Select, Medicare, Providence Preferred, Providence Health Plan, Regence Blue Cross Blue Shield, First Choice Health Network, First Health National Network, Pacificsource, Moda, OHA (fee for service only), First Health, and Premera Blue Cross. Please call us for a full list of providers. We would be happy to help check with your insurance regarding pre-approval.

*Unfortunately, Medi-cal currently does not cover TMS treatment in California. Please contact your Medi-cal provider to inquire further.

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