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Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in patients with depression, yet treatment response remains variable. While previous work has identified predictors of remission in younger adults, relatively little data exists in late-life depression (LLD). To address this gap, data from 164 participants with LLD from a randomized non-inferiority treatment trial comparing standard bilateral rTMS to bilateral theta burst stimulation (TBS) (ClinicalTrials.gov identifier: NCT02998580) were analyzed using binary logistic regression and conditional inference tree (CIT) modeling. Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. The CIT predicted a higher likelihood of achieving remission for patients with a total score of 19 or lower on the Montgomery-Åsberg Depression Rating Scale, 1 or fewer prior antidepressant treatment failures, and a total score of 23 or higher on the Montreal Cognitive Assessment. Our results indicate that older adults with lower severity of depression, fewer antidepressant treatment failures, and higher global cognition benefit more from current forms of rTMS. The results suggest that there is potentially higher value in using rTMS earlier in the treatment pathway for depression in older adults., Competing Interests: Declaration of competing interest KG, APT and CM declare no conflict of interest. LM has received research funding from the Alzheimer's Society of Canada, Centre for Aging and Brain Health Innovation, Ontario Ministry of Health and Long-Term Care, and Brainsway, Ltd. TKR has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, CAMH Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. TKR also received in-kind equipment support for an investigator-initiated study from Magstim, and in-kind research accounts from Scientific Brain Training Pro. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. He also currently serves on the scientific advisory board for Brainsway Inc. His-work has been supported by the National Institutes of Mental Health (NIMH), the Canadian Institutes of Health Research (CIHR), Brain Canada and the Temerty Family, Grant and Kreutzcamp Family Foundations. JD has received research support from NIH, CIHR, Brain Canada, Ontario Brain Institute, the Klarman Family Foundation, the Arrell Family Foundation, and the Buchan Family Foundation, in-kind equipment support for investigator-initiated trials from MagVenture, is an advisor for BrainCheck, Arc Health Partners and Salience Neuro Health, and is a co-founder of Ampa Health. SMM reports research support from the National Institutes of Health (NIH) / National Institute of Mental Health and the Brain & Behavior Research Foundation. He is a consultant for Pearson, Inc. He receives royalties from Guilford Press, Inc. SMN reports research and salary support from the Sunnybrook Health Sciences Centre Foundation, Harquail Centre for Neuromodulation; research support from the Brain and Behaviour Research Foundation Young Investigator Grant, Labatt Family Network Discovery Program and the Donald T Stuss Young Investigator Research Innovation Award. YN has received a Grant-in-Aid for Scientific Research (B) (21H02813) from the Japan Society for the Promotion of Science; research grants from Japan Agency for Medical Research and Development; investigator-initiated clinical study grants from Teijin Pharma and Inter Reha Co; research grants from the Watanabe Foundation and Daiichi Sankyo Scholarship Donation Program; speaker's honoraria from Sumitomo Pharma Co, Teijin Pharma, Takeda Pharmaceutical Co, Lundbeck Japan Co, and Viatris within the past 3 years outside the submitted work; and in-kind equipment support for investigator-initiated studies from Magventure, Inter Reha Co, and Miyuki Giken Co. BHM belongs to the following Boards: Member, Board of Trustees, Centre for Addiction and Mental Health, Toronto, Ontario. Current potential conflicts (and past five years: January 2018 -present): support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). DMB has received research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. He is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for two investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Multiple pharmacologic agents now have been approved in the United States and other countries as treatment to slow disease and clinical progression for Alzheimer's disease. Given these treatments have not been proven to lessen the cognitive deficits already manifested in the Alzheimer's Clinical Syndrome (ACS), and none are aimed for another debilitating dementia syndrome identified as primary progressive aphasia (PPA), there is an urgent need for new, safe, tolerable, and efficacious treatments to mitigate the cognitive deficits experienced in ACS and PPA. Noninvasive brain stimulation has shown promise for enhancing cognitive functioning, and there has been interest in its potential therapeutic value in ACS and PPA. This review critically examines the evidence of five technologies in ACS and PPA: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), repetitive transcranial magnetic stimulation (rTMS), and noninvasive vagus nerve stimulation (nVNS). Many randomized controlled trials of tDCS and rTMS report positive treatment effects on cognition in ACS and PPA that persist out to at least 8 weeks, whereas there are few trials for tACS and none for tRNS and nVNS. However, most positive trials did not identify clinically meaningful changes, underscoring that clinical efficacy has yet to be established in ACS and PPA. Much is still to be learned about noninvasive brain stimulation in ACS and PPA, and shifting the focus to prioritize clinical significance in addition to statistical significance in trials could yield greater success in understanding its potential cognitive effects and optimal parameters.

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute treatment, there are no published studies of continuation MST for the prevention of relapse., Methods: Patients with TRD with a DSM-IV diagnosis of major depressive disorder or bipolar disorder who met response criteria after acute MST were offered continuation MST in a prospective, open-label trial between February 2012 and June 2019. They received 12 continuation MST sessions with decreasing frequency over the course of 6 months, with additional booster sessions if their depression symptoms started to worsen. The primary outcome was relapse of depression or psychiatric hospitalization. Secondary outcomes included relapse of suicidal ideation and neurocognitive outcomes., Results: Thirty participants completing at least one assessment during continuation MST were included in the analysis; 10 (33.3%) relapsed, with no significant differences in survival distributions between unipolar and bipolar groups (χ 2  = 0.3, P  = .58). Mean (SD) survival time was 18.6 (1.6) weeks. All 17 participants who achieved resolution of baseline suicidality after acute MST remained free of suicidality during the continuation phase. Except for improvement in verbal fluency, neurocognitive test scores did not change during continuation MST., Conclusions: During 6 months of continuation MST, two-thirds of participants sustained improvements in depressive symptoms without any adverse cognitive effects. Future studies of continuation MST are warranted, particularly in comparison to ECT., Trial Registration: ClinicalTrials.gov identifier: NCT01596608., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

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.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level., Methods: A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression., Results: Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47)., Conclusion: A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability., (© 2017 Wiley Periodicals, Inc.)

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic intervention for neuropsychiatric illnesses and has demonstrated efficacy for treatment of major depression. However, an unresolved question is whether a course of rTMS treatment results in effects on cognitive functioning. In this systematic review and meta-analysis we aimed to quantitatively determine whether a course of rTMS has cognitive enhancing effects. We examined cognitive outcomes from randomised, sham-controlled studies conducted in patients with neuropsychiatric conditions where rTMS was administered to the dorsolateral prefrontal cortex (DLPFC) across repeated sessions, searched from PubMed/MEDLINE and other databases up until October 2015. Thirty studies met our inclusion criteria. Cognitive outcomes were pooled and examined across the following domains: Global cognitive function, executive function, attention, working memory, processing speed, visual memory, verbal memory and visuospatial ability. Active rTMS treatment was unassociated with generalised gains across the majority of domains of cognitive functioning examined. Secondary analyses revealed a moderate sized positive effect for improved working memory in a small number of studies in patients with schizophrenia (k = 3, g = 0.507, 95 % CI = [0.183-0.831], p < .01). Therapeutic rTMS when administered to the DLPFC in patients with neuropsychiatric conditions does not result in robust cognitive enhancing effects.

Transcranial magnetic stimulation (TMS) can be used to probe cortical function and treat neuropsychiatric illnesses. TMS has demonstrated neuroplastic effects akin to long-term potentiation and long-term depression, and therapeutic applications are in development for post-stroke recovery, Alzheimer's disease, and depression in seniors. Here, we discuss two new directions of TMS research relevant to cerebral aging and cognition. First, we introduce a paradigm for enhancing cognitive reserve, based on our research in sleep deprivation. Second, we discuss the use of magnetic seizure therapy (MST) to spare cognitive functions relative to conventional electroconvulsive therapy, and as a means of providing a more potent antidepressant treatment when subconvulsive TMS has shown modest efficacy in seniors. Whether in the enhancement of cognition as a treatment goal, or in the reduction of amnesia as a side effect, these approaches to the use of TMS and MST merit further exploration regarding their clinical potential.

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

Magnetic seizure therapy (MST) is a novel neurotherapeutic intervention in development for the treatment of major affective disorders. Like other neurotherapeutic strategies such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS), a primary interest will be to monitor the associated neurocognitive effects. Thus, the purpose of this systematic review was to synthesize the available data on the neurocognitive effects of MST. The authors performed two independent literature searches with the following terms terms: MST, magnetic, magnetic seizure therapy, depression, neurocognition, cognitive, preclinical. We included in this review a total of eleven articles that mentioned MST and neurocognition in the abstract. The articles were divided into three methodological domains that included virtual computer simulations, preclinical studies, and clinical investigations. Collectively, the available evidence suggests MST has little to no adverse cognitive effects. Specifically, virtual computer simulations found the magnetic field was localized to grey matter, and preclinical studies found no neurocortical or neurocognitive sequelae. Clinical investigations found MST to be associated with rapid reorientation and intact anterograde and retrograde memory. Future investigations using translational methods are warranted to confirm these findings and to further determine the effects of MST on neurocognitive functions.

Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Psychomotor retardation is a long established component of depression that can have significant clinical and therapeutic implications for treatment. Due to its negative impact on overall function in depressed patients, we review its biological correlates, optimal methods of measurement, and relevance in the context of therapeutic interventions. The aim of the paper is to provide a synthesis of the literature on psychomotor retardation in depression with the goal of enhanced awareness for clinicians and researchers. Increased knowledge and understanding of psychomotor retardation in major depressive disorder may lead to further research and better informed diagnosis in regards to psychomotor retardation. Manifestations of psychomotor retardation include slowed speech, decreased movement, and impaired cognitive function. It is common in patients with melancholic depression and those with psychotic features. Biological correlates may include abnormalities in the basal ganglia and dopaminergic pathways. Neurophysiologic tools such as neuroimaging and transcranial magnetic stimulation may play a role in the study of this symptom in the future. At present, there are three objective scales to evaluate psychomotor retardation severity. Studies examining the impact of psychomotor retardation on clinical outcome have found differential results. However, available evidence suggests that depressed patients with psychomotor retardation may respond well to electroconvulsive therapy (ECT). Current literature regarding antidepressants is inconclusive, though tricyclic antidepressants may be considered for treatment of patients with psychomotor retardation. Future work examining this objective aspect of major depressive disorder (MDD) is essential. This could further elucidate the biological underpinnings of depression and optimize its treatment., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is a form of neurostimulation therapy that was recently approved by the Food and Drug Administration for the treatment of depression. Repetitive transcranial magnetic stimulation is considered noninvasive and relatively safe; however, there have been reports of scalp pain during and at the site of stimulation. This case report documents the use of topical lidocaine to reduce scalp pain during rTMS administration. All patients had a diagnosis of major depressive disorder according to research diagnostic criteria and were washed off antidepressant medications before treatment. Patients were given active rTMS treatment during a masked, open-label, or long-term follow-up treatment schedule. Treatment was delivered to the left dorsolateral prefrontal cortex at 120% of the patient's observed motor threshold. Ten patients received 3000 magnetic pulses per session with an on time of 4 seconds and an off time of 26 seconds. Patients who reported pain during stimulation were given topical lidocaine HCl 2%, which was applied 20 minutes before treatment. Patients reported mixed outcomes of using topical lidocaine to reduce scalp pain during stimulation. Half of the patients reported no significant reduction in pain, whereas the other half indicated a noticeable decrease during rTMS. As a case report, our study has limited results. Given the recent approval of rTMS for the treatment of depression, additional studies are warranted to determine optimal methods of reducing scalp pain.

Electroconvulsive therapy (ECT) and ablative neurosurgical procedures are established interventions for treatment-resistant depression (TRD), but their use may be limited in part by neuropsychological adverse effects. Additional neuromodulation strategies are being developed that aim to match or exceed the efficacy of ECT/ablative surgery with a better neurocognitive side effect profile. In this review, we briefly discuss the neurocognitive effects of ECT and ablative neurosurgical procedures, then synthesize the available neurocognitive information for emerging neuromodulation therapies, including repetitive transcranial magnetic stimulation, magnetic seizure therapy, transcranial direct current stimulation, vagus nerve stimulation, and deep brain stimulation. The available evidence suggests these procedures may be more cognitively benign relative to ECT or ablative neurosurgical procedures, though further research is clearly needed to fully evaluate the neurocognitive effects, both positive and negative, of these novel neuromodulation interventions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging because of recurrences and limited modalities. Selective serotonin reuptake inhibitors and cognitive behavioral therapy are considered the standard of care in severe or treatment-resistant MDD in this age group. However, responses to these interventions are often suboptimal. A growing body of research supports the efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of MDD in adults. Induced seizures are a primary safety concern, although this is rare with appropriate precautions. There is, however, limited experience with rTMS as a therapeutic intervention for adolescent psychiatric disturbances. This review will summarize the rTMS efficacy and safety data in adults and describe all published experience with adolescent MDD. Applications in other adolescent psychiatric illnesses such as schizophrenia and attention-deficit/hyperactivity disorder are reviewed. Safety and ethical issues are paramount with investigational treatments in adolescent psychiatric illnesses. However, further research with rTMS in adolescent MDD is imperative to establish standards for optimal stimulation site, treatment parameters, and its role in treatment algorithms. These may diverge from adult data. Early intervention with neuromodulation could also hold the promise of addressing the developmental course of dysfunctional neurocircuitry.

Introduction: Simultaneously acquiring functional Near Infrared Spectroscopy (fNIRS) during Transcranial Magnetic Stimulation (rTMS) offers the possibility of directly investigating superficial cortical brain activation and connectivity. In addition, the effects of rTMS in distinct brain regions without quantifiable behavioral changes can be objectively measured., Methods: Healthy, nonmedicated participants age 18-50 years were recruited from the local community. After written informed consent was obtained, the participants were screened to ensure that they met inclusion criteria. They underwent two visits of simultaneous rTMS/fNIRS separated by 2 to 3 days. In each visit, the motor cortex and subsequently the prefrontal cortex (5 cm anterior to the motor cortex) were stimulated (1 Hz, max 120% MT, 10 s on with 80 s off, for 15 trains) while simultaneous fNIRS data were acquired from the ipsilateral and contralateral brain regions., Results: Twelve healthy volunteers were enrolled with one excluded prior to stimulation. The 11 participants studied (9 male) had a mean age of 31.8 (s.d. 10.2, range 20-49) years. There was no significant difference in fNIRS between Visit 1 and Visit 2. Stimulation of both the motor and prefrontal cortices resulted in a significant decrease in oxygenated hemoglobin (HbO(2)) concentration in both the ipsilateral and contralateral cortices. The ipsilateral and contralateral changes showed high temporal consistency., Discussion: Simultaneous rTMS/fNIRS provides a reliable measure of regional cortical brain activation and connectivity that could be very useful in studying brain disorders as well as cortical changes induced by rTMS.

BackgroundElectroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood.Methods/designThis neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity.DiscussionECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments.Trial registrationClinicalTrials.gov NCT03191058 . Registered on June 19, 2017.

Summary: Repetitive transcranial magnetic stimulation (rTMS) is used for treatment of late-life depression. In the FOUR-D study, sequential bilateral theta-burst stimulation (TBS) had comparable remission rates to standard bilateral rTMS. Data were analysed from the FOUR-D trial to compare remission rates between two types of rTMS based on the number and class of prior medication trials. The remission rate was higher in participants with ≤1 previous trial (43.9%) than in participants with 2 previous trials (26.5%) or ≥3 previous trials (24.6%; χ² = 6.36, d.f. = 2, P = 0.04). Utilising rTMS earlier in late-life depression may lead to better outcomes. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Abstract: Electroconvulsive therapy (ECT) is an effective treatment for severe depression; however, the induced therapeutic seizure acts on the autonomic nervous system and results in significant cardiac effects. This is an important consideration particularly in the elderly. Magnetic seizure therapy (MST) is in development as a less invasive alternative, but its effects on cardiac function have not been studied. We sought to model those effects in nonhuman primates to inform the development of safer neurostimulation interventions. Twenty four rhesus monkeys were randomly assigned to receive 6 weeks of daily treatment with electroconvulsive stimulation (ECS), magnetic seizure therapy (MST) or anesthesia-alone sham. Digitally acquired ECG and an automated R-wave and inter-R interval (IRI) sampling were used to measure intervention effects on heart rate (HR). Significant differences between experimental conditions were found in the HR as evidenced by changes in the immediate post-stimulus, ictal and postictal epochs. Immediate post-stimulus bradycardia was seen with ECS but not with MST. ECS induced significantly more tachycardia than MST or sham in both the ictal and postictal periods. MST resulted in a small, but statistically significant increase in HR during the postictal period relative to baseline. HR was found to increase by 25% and 8% in the ECS and MST conditions, respectively. MST resulted in significantly less marked sympathetic and parasympathetic response than did ECS. This differential physiological response is consistent with MST having a more superficial cortical site of action with less impact on deeper brain structures implicated in cardiac control relative to ECT. The clinical relevance of the topographical seizure spread of MST and its associated effects on the autonomic nervous system remain to be determined in human clinical trials. [Copyright &y& Elsevier]