Magnetic Seizure Therapy Research Articles

Subgenual cingulate connectivity and hippocampal activation are related to MST therapeutic and adverse effects

Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Here we combine transcranial magnetic stimulation with electroencephalography (TMS-EEG) to evaluate the effects of MST on connectivity and activation between the DLPFC, the SGC and hippocampus (Hipp) in patients with TRD. The TMS-EEG was collected from 31 TRD patients prior to and after an MST treatment trial. Through TMS-EEG methodology we evaluated significant current scattering (SCS) as an index of effective connectivity between the SGC and left DLPFC. Significant current density (SCD) was used to assess activity at the level of the Hipp. The SCS between the SGC and DLPFC was reduced after the course of MST (p < 0.036). The DLPFC-SGC effective connectivity reduction correlated with the changes in Hamilton depression score pre-to-post treatment (R = 0.46; p < 0.031). The SCD localized to the Hipp was reduced after the course of MST (p < 0.015), and the SCD change was correlated with montreal cognitive assessment (MOCA) scores pre-post the course of MST (R = −0.59; p < 0.026). Our findings suggest that MST treatment is associated with SGC-DLPFC connectivity reduction and that changes to cognition are associated with Hipp activation reduction. These findings demonstrate two distinct processes which drive efficacy and side effects separately, and might eventually aid in delineating physiological TRD targets in clinical settings.

Shorter recovery times and better cognitive function-A comparative pilot study of magnetic seizure therapy and electroconvulsive therapy in patients with depressive episodes.

IntroductionMagnetic seizure therapy (MST) is a new convulsive therapy that is as effective as traditional electroconvulsive therapy (ECT) in treating depression but with fewer cognitive side effects. The aim of this study was to compare the efficacy and cognitive effects between MST (100 Hz applied over the vertex) and bifrontal ECT for treating patients with depressive episodes.MethodsForty‐five patients with depressive episodes were enrolled, with 18 receiving MST and 27 receiving ECT. MST was administered over the vertex with 100 Hz frequency. Treatment consisted of six sessions. The 17‐item Hamilton Rating Scale for Depression (HAMD‐17) was used to assess the severity of depression. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognition. Assessments were performed at baseline and after the third and sixth treatment sessions.ResultsBoth MST and ECT improved the patients’ depressive symptoms significantly, yet no significant difference was found between the two groups (p > .05). The response rates and remission rates of MST and ECT were 72.2% versus 81.5% and 61.1% versus 63.0%, respectively. The MST group showed significant improvements in immediate memory (p < .001), delayed memory (p = .002), and attention (p < .001) than ECT. The recovery times for consciousness (p < .001), spontaneous breathing (p < .001), and orientation (p < .001) were shorter in MST group than ECT group. RBANS improvements were negatively correlated with the recovery time for orientation (r = .561, p < .001).ConclusionMagnetic seizure therapy showed similar efficacy to bifrontal ECT for treating depressive episodes. While MST may be an effective alternative to ECT, larger randomized trials are needed.

111 - Surface neuromodulation (TMS and tDCS) for therapy of cognitive and psychiatric disorders

The field of neuromodulation has progressed significantly over the past two decades. It is evident that application of electrical (via tDCS, transcranial direct current stimulation) or magnetic (via rTMS, repetitive transcranial magnetic stimulation) brain stimulation over the skull surface can effect change in brain function, which appears sufficiently robust to have a therapeutic effect. Sometimes the neuromodulation is best coupled with other forms of training or rehabilitation for best efficacy. What are the most promising approaches? What conditions appear to benefit? What are the situations/diseases/ disease states where neuromodulation is sufficiently well-proven now (or may be so in the future) that clinicians should start to consider its use in their psychogeriatric practice? We will review studies showing that tDCS can have a therapeutic effect in dementia, stroke, depression, and a range of other psychiatric conditions. Recent work is showing that with tDCS one can achieve improvement in picture naming, executive function, and memory in Alzheimer Disease and Frontotemporal dementia (Howard Chertkow presentation, Baycrest Health Sciences, Toronto). In stroke rehabilitation, rTMS treatment has been shown to aid in motor and language recovery (Alex Thiel, McGill University). There is now sufficient evidence that tDCS and Magnetic Seizure therapy are beneficial in depression, that these can now become part of the therapeutic armamentarium in selected cases (Jeff Daskalakis, University of Toronto). A range of other neuropsychiatric conditions can also be considered for neuromodulation therapy with rTMS (Daniel Blumberger, University of Toronto, CAMH).By attending this symposium, a physician or health care professional will become familiar with the latest research into neuromodulation and its role in current therapy of neurological and psychiatric diseases.

A pilot study of magnetic seizure therapy for treatment-resistant obsessive-compulsive disorder.

There is growing interest in the potential of neuromodulation options in treatment-resistant obsessive-compulsive disorder (OCD). Magnetic seizure therapy (MST), is a new treatment intervention in which generalized seizures are induced with transcranial magnetic stimulation. We conducted a pilot study to assess the efficacy and cognitive effects of MST in patients with treatment-resistant OCD. In an open-label pilot study, participants with treatment-resistant OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores of ≥16 were treated with up to 24 acute treatments. The primary clinical outcomes were clinical response (Y-BOCS score reduction ≥30%) and remission (final Y-BOCS score ≤8). A neurocognitive battery, the Quick Inventory for Depressive Symptoms-Self Report (QIDS-SR), the Beck Scale for Suicidal Ideation (SSI), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were also completed as secondary measures. Ten participants with OCD who had not responded to medications or psychotherapy enrolled in the study and seven completed an adequate trial (defined as ≥8 treatments). MST was associated with minimal cognitive effects except for some decrease in autobiographical memory and no serious adverse effects. Only one participant met the predefined criteria for response, and none for remission. The baseline and endpoint Y-BOCS scores were not statistically different. Overall, MST was not beneficial in a small group of patients with treatment-resistant OCD. At this time, other studies of MST for OCD are not warranted until different coil placements targeting other brain circuits can be proposed.

Resting-state electroencephalographic functional network alterations in major depressive disorder following magnetic seizure therapy

Magnetic seizure therapy (MST) is emerging as a safe and well-tolerated experimental intervention for major depressive disorder (MDD), with very minimal cognitive side-effects. However, the underlying mechanism of action of MST remains uncertain. Here, we used resting-state electroencephalography (RS-EEG) to characterise the physiological effects of MST for treatment resistant MDD. We recorded RS-EEG in 21 patients before and after an open label trial of MST applied over the prefrontal cortex using a bilateral twin coil. RS-EEG was analysed for changes in functional connectivity, network topology, and spectral power. We also ran further baseline comparisons between the MDD patients and a cohort of healthy controls (n = 22). Network-based connectivity analysis revealed a functional subnetwork of significantly increased theta connectivity spanning frontal and parieto-occipital channels following MST. The change in theta connectivity was further found to predict clinical response to treatment. An additional widespread subnetwork of reduced beta connectivity was also elucidated. Graph-based topological analyses showed an increase in functional network segregation and reduction in integration in the theta band, with a decline in segregation in the beta band. Finally, delta and theta power were significantly elevated following treatment, while gamma power declined. No baseline differences between MDD patients and healthy subjects were observed. These results highlight widespread changes in resting-state brain dynamics following a course of MST in MDD patients, with changes in theta connectivity providing a potential physiological marker of treatment response. Future prospective studies are required to confirm these initial findings.

Magnetic Seizure Therapy for Suicidality in Treatment-Resistant Depression

There is an unmet need for effective treatments for suicidality in mental disorders. Magnetic seizure therapy (MST) has been investigated as an alternative to electroconvulsive therapy, a known effective treatment for suicidality, in the management of treatment-resistant major depressive disorder, with promising findings. Yet, there are very limited data on the association of MST with suicidality directly. It is important to explore the potential of MST as a viable treatment alternative to electroconvulsive therapy for suicidality. To determine the association of MST with suicidality in patients with treatment-resistant major depressive disorder. This nonrandomized controlled trial took place at a single tertiary care psychiatric facility in Canada. It followed an open-label study design with consecutive treatment cohorts. Consecutive groupings of 67 patients with treatment-resistant major depressive disorder and with baseline suicidality present were treated for up to 24 treatments. The study was run from February 2012 through June 2019. Patients were followed up for 6 months at the end of the treatment period. This post hoc secondary analysis of the trial was performed from January to November 2019. MST was delivered at 100% stimulator output over the prefrontal cortex with low (25 Hz), moderate (50 or 60 Hz), or high (100 Hz) frequency, for a maximum of 24 sessions. Remission from suicidality was measured as an end point score of 0 on the Beck Scale for Suicidal Ideation. A linear mixed model was used to assess the trajectory of Beck Scale for Suicidal Ideation scores. A total of 67 patients (mean [SD] age, 46.3 [13.6] years; 40 women [60.0%]) received a mean (SD) of 19.5 (5.1) MST treatments. The overall number of patients achieving remission was 32 (47.8%). Sixteen patients (55.2%) receiving low-frequency MST achieved remission, as well as 12 patients (54.5%) in the moderate-frequency group, and 4 patients (25.0%) in the high-frequency group. The linear mixed model revealed an association of time with Beck Scale for Suicidal Ideation scores (F8,293.95 = 5.73; P < .001). These findings suggest that MST may be an effective treatment for suicidality, and sensitivity analysis shows this may be particularly so at low and moderate frequencies. Future studies should directly compare MST with electroconvulsive therapy for treating suicidality and should evaluate MST as a treatment for suicidality across mental disorders. ClinicalTrials.gov Identifier: NCT01596608.

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain.

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more “precision-oriented” practice.

The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression.

In this review, the efficacy and safety of FDA approved neuromodulation devices (electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS)), as well as emerging neuromodulation treatments currently under investigation. ECT is the "gold standard" somatic therapy for treatment resistant depression (TRD). Although the clinical benefits are outweighed by potential cognitive and cardiovascular side effects in majority of cases, it remains unfairly stigmatized. TMS has few cognitive or somatic side effects but is not as effective the treatment of psychotic depression or more treatment resistant depression in elders. VNS has limited data in older patients but has been shown to be effective in chronic, treatment resistant adults. Several investigative neuromodulation treatments including magnetic seizure therapy (MST), focal electrically administered seizure therapy (FEAST), transcutaneous VNS (tVNS), transcranial direct current stimulation (tDCS), and deep brain simulation (DBS) shown promise in geriatric TRD. ECT, TMS and VNS are effective treatment for late-life depression, and research has continued to refine the techniques. Investigative neuromodulation techniques are promising, but evidence for the safety and efficacy of these devices in the geriatric population is needed.

Factor Structure of the Hamilton Depression Rating Scale During Electroconvulsive Therapy and Magnetic Seizure Therapy in the Treatment of Major Depression

Magnetic seizure therapy (MST), in which seizures are induced using high-dose repetitive transcranial magnetic stimulation, offers similar efficacy as electroconvulsive therapy (ECT), but with lower side effects. We investigate how these treatment modalities compare in their effects on symptom dimensions of depression.

Treatment of Suicidality in Bipolar Depression With Magnetic Seizure Therapy: Clinical Effects and Neurophysiological Correlates

Electroconvulsive therapy (ECT) is highly effective for acute suicidal ideation but is limited by significant adverse cognitive effects. Magnetic Seizure Therapy (MST) is a novel convulsive treatment with more focal stimulation that has been found to have no adverse cognitive effects and may be effective in bipolar depression. There is evidence that cortical inhibition measured with transcranial magnetic stimulation and electroencephalography (TMS-EEG) may predict treatment response.

Predictors of Remission to Open Label Magnetic Seizure Therapy for Major Depressive Disorder: A Secondary Analysis

Predictors of Remission to Open Label Magnetic Seizure Therapy for Major Depressive Disorder: A Secondary Analysis

P7 Characterising functional connectivity changes following magnetic seizure therapy for major depressive disorder: A resting-state EEG analysis

P7 Characterising functional connectivity changes following magnetic seizure therapy for major depressive disorder: A resting-state EEG analysis

NIMH Director to Discuss Advances in Treating Major Depression

Back to table of contents Previous article Next article APA & MeetingsFull AccessNIMH Director to Discuss Advances in Treating Major DepressionNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:14 Feb 2020https://doi.org/10.1176/appi.pn.2020.2b4AbstractEfforts to build upon the successful FDA approvals of esketamine and brexanolone are a part of the National Institute of Mental Health’s research priorities, as the institute looks toward a future of precision depression care.NIMH Director Joshua Gordon, M.D., Ph.D., has planned an interactive session for APA’s Annual Meeting so that he can learn directly from APA members about their views and priorities for research.Chia-Chi Charlie ChangThe Food and Drug Administration approval of the fast-acting medications esketamine and brexanolone in March 2019 symbolized a significant leap forward in the treatment of major depression, but challenges remain.“Due to risks associated with each drug, patients can’t simply pick up a prescription for esketamine or brexanolone at their local pharmacy,” said Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental Health (NIMH) in comments submitted to Psychiatric News. Instead, patients must receive the medications under the supervision of a health care professional in a certified medical office.“The hard work of trying to harness the full potential of these medications and other available treatments continues apace,” Gordon continued. Still, the journey of esketamine and brexanolone offers a compelling tale of how NIMH-supported bench-to-bedside research can advance the understanding of the brain and lead to therapeutic breakthroughs. The story of these drugs, as well as NIMH’s ongoing research efforts in depression, will be a focus of Gordon’s presentation titled “The NIMH: Programs, Priorities, and Plans” at the APA Annual Meeting.Gordon noted that a research team led by Carlos Zarate, M.D., chief of the NIMH Section on the Neurobiology and Treatment of Mood Disorders and chief of the institute’s Experimental Therapeutics and Pathophysiology Branch, has identified one promising esketamine derivative—the metabolite hydroxynorketamine—that might produce robust antidepressant effects with minimal undesirable symptoms or risk of misuse. Scientists from NIMH, the National Institute on Aging, and the National Center for Advancing Translational Science are getting ready to test this compound in patients with treatment-resistant depression.NIMH is also supporting research on other modes of treatment for depression such as brain stimulation. As with ketamine and brexanolone, brain stimulation therapies like electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) can provide rapid symptom relief for many patients. Sarah H. Lisanby, M.D., director of NIMH’s Noninvasive Neuromodulation Unit, and colleagues have developed tools to improve the safety and efficacy of these stimulation therapies and have advanced new methods such as magnetic seizure therapy, which has features of both ECT and TMS.“Today, people who are living with depression have more treatment options available to them than ever before,” said Gordon. “But there is still a long way to go in understanding how to best tailor treatments to each person. Speeding up the treatment selection process could prevent months or even years of debilitating symptoms.”An active focus of NIMH-supported research, therefore, is to build on the emerging understanding of the heterogeneity of depression so that individuals can receive optimal treatment sooner. Researchers have begun to make use of “big data” and advances in neuroscience to develop algorithms that could help determine which treatment option is best for individual patients. “While a long way off from public use, [using] genetic [information] to match people with the medication is another possible approach that is likely to benefit from ongoing research,” Gordon added.“Together, these many lines of NIMH-funded research have the potential to produce precision medicine that could change the way we think about and treat depression,” he said. “The road from basic science discoveries to novel therapies may be long and winding, but we already have evidence that it can lead to success.”■“The NIMH: Programs, Priorities, and Plans” will be held Monday, April 27, from 8 a.m. to 9:30 a.m. ISSUES NewArchived

Magnetic seizure therapy for treatment-resistant depression

Magnetic seizure therapy for treatment-resistant depression

Management of Treatment-Resistant Depression: Challenges and Strategies.

Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder which does not respond to traditional and first-line therapeutic options. There are several definitions and staging models of TRD and a consensus for each has not yet been established. However, in common for each model is the inadequate response to at least 2 trials of antidepressant pharmacotherapy. In this review, a comprehensive analysis of existing literature regarding the challenges and management of TRD has been compiled. A PubMed search was performed to assemble meta-analyses, trials and reviews on the topic of TRD. First, we address the confounds in the definitions and staging models of TRD, and subsequently the difficulties inherent in assessing the illness. Pharmacological augmentation strategies including lithium, triiodothyronine and second-generation antipsychotics are reviewed, as is switching of antidepressant class. Somatic therapies, including several modalities of brain stimulation (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation) are detailed, psychotherapeutic strategies and subsequently novel therapeutics including ketamine, psilocybin, anti-inflammatories and new directions are reviewed in this manuscript. Our review of the evidence suggests that further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD.

Accelerated magnetic seizure therapy (aMST) for treatment of major depressive disorder: A pilot study

Background: Magnetic Seizure therapy (MST) is an emerging treatment for major depressive disorder (MDD) that is associated with fewer cognitive side effects compared to electroconvulsive therapy. The present pilot study sought to investigate whether daily MST treatments were associated to antidepressant effect and assess cognitive side effects associated with an accelerated MST (aMST) treatment schedule. Methods: Fifteen MDD patients underwent a six-day course of MST treatment to the vertex following assessment of symptom severity and neuropsychological testing. The primary outcome was severity on the Hamilton Rating Scale for Depression 17-item (HRSD-17). Patient also underwent neuropsychological assessment with the RBANS and Stroop Colour-Word test. Results: There were no instances of delirium or disturbance of consciousness following aMST sessions. Patients showed significant decreases on indices of depression and anxiety symptoms, with 9 (60%) patients showing a clinical response and 7 (47%) patients experiencing remission. Significant improvements were reported in RBANS total score, as well as indices of immediate memory and delayed memory. No changes at follow-up were reported for visuospatial/constructional, language, and attention RBANS indices, nor for Stroop Colour/Word performance. Limitations: The results should be interpreted with caution as they are part of a non-randomized, open-label pilot study. Further, the short duration of the study does not provide longitudinal follow-up to determine whether treatment response lasts a meaningful duration of time. Conclusions: aMST well tolerated without significant evidence of cognitive side effects and rapid improvement in symptoms. Further research is required to fully characterize these changes and replicate them in independent samples.

Effects of magnetic seizure therapy on anterograde and retrograde amnesia in treatment-resistant depression.

Electroconvulsive therapy (ECT) is the gold standard for treatment-resistant depression (TRD). However, cognitive side effects, mainly anterograde and retrograde amnesia, frequently occur. Magnetic seizure therapy (MST) is tested using more focal seizure induction. However, the suggestion MST may be more beneficial than ECT because it causes fewer amnesia have not yet been comprehensively investigated using common neuropsychological testing specifically for ECT. We aimed to examine whether MST causes anterograde and retrograde amnesia. Ten patients with TRD were treated with MST (8.9 [2] treatments) at 100% machine output, a frequency of 100 Hz and 657.4 (62) pulses per train. The short form of the Autobiographical Memory Inventory was administered to test retrograde amnesia. Furthermore, an extended neuropsychological test battery, including verbal and nonverbal recall as well as recognition tasks, was used. We observed changes in retrograde amnesia, although they were not clinically relevant (mean: -0.42 ± 0.14). Furthermore, no anterograde amnesia as well as no effects on global cognitive status, attention, language, and executive functions after MST were measured. The cognitive safety and efficacy of MST in patients with TRD were indicated. However, the main limitations of the present study were the small sample and as a consequence, the low statistical power to detect changes after treatment. Therefore, our findings require replication in further studies. In addition, a direct comparison between MST and ECT in a larger sample should be performed before MST can be discussed as an alternative treatment approach to ECT in clinical practice.

Magnetic seizure therapy (MST) for major depressive disorder.

Electroconvulsive therapy (ECT) is effective for major depressive disorder (MDD) but its effects on memory limit itswidespread use. Magnetic seizure therapy (MST) is a potential alternative to ECT that may not adversely affect memory. In the current trial, consecutive patients with MDD consented to receive MST applied over the prefrontal cortex according to an open-label protocol. Depressive symptoms and cognition were assessed prior to, during and at the end of treatment. Patients were treated two to three times per week with high-frequency MST (i.e., 100 Hz) (N = 24), medium frequency MST (i.e., 60 or 50 Hz) (N = 26), or low-frequency MST (i.e., 25 Hz MST) (N = 36) using 100% stimulator output. One hundred and forty patients were screened; 86 patients with MDD received a minimum of eight treatments and were deemed to have an adequate course of MST; and 47 completed the trial per protocol, either achieving remission (i.e., 24-item Hamilton Rating Scale for Depression score <10 and a relative reduction of >60% at two consecutive assessments; n = 17) or received a maximum of 24 sessions (n = 30). High-frequency (100 Hz) MST produced the highest remission rate (33.3%). Performance on most cognitive measures remained stable, with the exception of significantly worsened recall consistency of autobiographical information and significantly improved brief visuospatial memory task performance. Under open conditions, MST led to clinically meaningful reduction in depressive symptoms in patients with MDD and produced minimal cognitive impairment. Future studies should compare MST and ECT under double-blind randomized condition.

Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis

ObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.DesignSystematic review with pairwise and network meta-analysis.Data sourcesElectronic search...

難治性うつ病に対する反復性経頭蓋磁気刺激療法（rTMS）および磁気けいれん療法（MST）の臨床応用

難治性うつ病に対する反復性経頭蓋磁気刺激療法（rTMS）および磁気けいれん療法（MST）の臨床応用