Major depressive disorder (MDD) represents a major global health challenge, with a significant proportion of patients being resistant to drug treatment (TRD). Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the treatment of MDD/TRD, with a single stimulation session per day for five days per week over several weeks (the "standard" protocol). The two main paradigms used are high-frequency rTMS and intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (DLPFC). Accelerated TMS (aTMS) protocols aim to make the treatment more effective, or at least more rapidly effective, by delivering more stimulations in a shorter time, which could also facilitate the implementation of the protocols for a larger number of patients. In this systematic literature review, articles comparing in the same study an aTMS protocol to a standard or sham rTMS protocol were retained for analysis. Thus, 23 articles were retained and the analysis focused on the efficacy of aTMS protocols used for the treatment of depression (MDD/TRD) as well as on the impact of various stimulation parameters, such as stimulation pattern, intersession interval, dosage, and methods of cortical targeting. Although some studies did not report significant differences between aTMS and standard or sham protocols, others suggested potential advantages of aTMS, such as twice-daily HF-rTMS of the left DLPFC or more intensive iTBS protocols with a long interval between two sessions and personalized cortical targeting. Our results highlight the influence of the number of sessions or pulses per session (dosage), the duration of the interval between sessions, and the precision of target localization (using image-guided neuronavigation) on therapeutic efficacy. However, limitations in sample size, few independent studies replicating the same methodology, and variability in the clinical profile of treated patients, given different definitions of treatment resistance or the presence of comorbidities, hamper definitive conclusions.

Transcranial magnetic stimulation (TMS) applies electromagnetic pulses to stimulate cortical neurons. The antidepressant effect of the repetitive application of TMS (rTMS) was first shown nearly three decades ago. The therapeutic potential of TMS has been extensively investigated, mostly in treatment-resistant depression (TRD). Studies have extensively evaluated stimulation parameters, treatment schedules, methods to localize the stimulation target, and different magnetic coil designs engineered for desired stimulation breadth and depth. Several of these stimulation protocols and coils/devices have received U.S. Food and Drug Administration (FDA) clearance for application in TRD and other neuropsychiatric disorders, such as obsessive-compulsive disorder. Some stimulation protocols, while not FDA-cleared, have substantial clinical trial-derived evidence to support their safety and antidepressant efficacy. The proliferation of rTMS translational and clinical research has resulted in the field's advancement. This clinician-oriented review contains an overview of fundamental TMS principles, physiological effects, and studies of rTMS in TRD. Also discussed are two innovations that are increasingly applied in the clinic: theta burst stimulation and accelerated scheduling. A synthesis of the key clinical considerations given to patient assessment and safety, treatment setup, and the minimization and management of adverse effects is provided.

Adolescent major depressive disorder (MDD) is a prevalent and serious mental health condition. Pharmacological treatments are commonly used but often have poor tolerability and severe side effects, such as suicidal ideation. Deep transcranial magnetic stimulation (TMS) is currently cleared treating MDD in individuals 22-86 years old. This post-marketing surveillance study was designed to evaluate the safety and efficacy of using this tool as a treatment for MDD in younger patients. Data were collected from 56 sites, resulting in 1257 patients that met inclusion criteria (e.g. 11-21 years old, H1 coil, 18 Hz or iTBS, treatment-resistant MDD). Treatment was well tolerated in these younger patients, with an adverse event rate comparable to adults. After 30 sessions the response/remission rates were HDRS: 58.3 %/ 48.6 %, PHQ9:64.4 %, 25.5 %. After 36 sessions the response/remission rates were HDRS: 75.0 %/58.3 %, PHQ9:74.6 %/34.6 %. Median onset of response & remission was after 13 & 20 sessions respectively. Kaplan-Meier analysis showed 80 % of patients responded by 20 sessions and 90 % by 36 sessions. The outcomes from iTBS (1800 pulses) and 18 Hz were not significantly different (Fisher's exact test, p>0.05). There was a significant decrease in depression severity after treatment (p<0.0001, Chi-square test; PHQ-9 categorical distribution). Anxiety symptoms also improved in the majority of patients, with a response/remission rate of 66 %/40.2 % after 36 sessions (GAD-7). As the largest naturalistic study to date, these data demonstrate Deep TMS is a safe and effective therapeutic option for adolescents and young adults suffering from MDD when delivered under routine outpatient treatment conditions.

To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for managing upper limb muscular spasticity after stroke, and to examine its therapeutic effects on spasticity and motor function in the upper limb. A total of 110 post-stroke patients with upper limb spasticity were randomly assigned to the experimental or the control group. The experimental group received rTMS in conjunction with conventional rehabilitation therapy. The affected side of the head received daily treatment for 20 min each at Erb's point and the stimulation point, totaling 15 sessions over six days per week. The stimulation frequencies were 10 Hz (high frequency, M1 region) and 1 Hz (low frequency, Erb's point), with an intensity at 120% of the threshold. The control group received sham stimulation alongside conventional rehabilitation therapy. Assessments including the Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment for Upper Extremity (FM-UE), were also conducted before treatment initiation and after 15 rounds of rTMS. Post hoc subgroup analyses were conducted using independent-sample t-tests for FM-UE scores and Mann-Whitney U tests for MAS scores to assess heterogeneity in treatment responses by stroke type (cerebral infarction vs. intracerebral hemorrhage). Among these 110 patients, 25 patients were excluded from the study for various reasons. Hence, 53 patients were included in the control group and 32 patients were included in the experimental group. Following 15 rounds of rTMS, the experimental group exhibited a reductions in MAS score (P = 0.004). FM-UE scores increased significantly in both groups (both P < 0.05), with significant improvement observed in the experimental group (P < 0.05). Subgroup analyses revealed no significant differences in FM-UE or MAS outcomes between stroke types, likely due to the limited sample size of intracerebral hemorrhage participants (experimental group: n = 8; control group: n = 16). rTMS effectively alleviates upper limb spasticity and enhances motor function after stroke by modulating cortical and spinal nerve excitability.

Background/Objectives: Transcranial magnetic stimulation (TMS) is a non-invasive and well-tolerated treatment, offering an effective alternative for elderly patients with depression, especially when side effects or comorbidities limit medication. Methods: This scoping review analyzes 16 studies published over the past seven years, to evaluate the efficacy, safety, and clinical applications of TMS in older adults with depression. Results: The review examines various TMS modalities, including repetitive TMS (rTMS), deep TMS, and theta burst stimulation (TBS), with most protocols targeting the dorsolateral prefrontal cortex (DLPFC). Adverse effects were rare, mild, and transient, supporting the treatment's safety profile. Pharmacological co-treatment was common but not essential for clinical improvement, highlighting TMS's potential as a standalone therapy. A subset of studies used neuroplasticity (SICI, ICF, CSP) or neuroimaging measures (MRI and MRI-based neuronavigation), revealing that age-related cortical inhibition may limit plasticity rather than depression itself. Conclusions: Overall, TMS demonstrates promising effectiveness and tolerability in managing late-life depression. Across studies, remission rates varied from 20% to 63%, with higher efficacy generally observed in bilateral stimulation or high-frequency protocols. Standardization of protocols and further research into individualized targeting and long-term outcomes are warranted to support broader clinical adoption.

Accelerated forms of repetitive transcranial magnetic stimulation (rTMS) are proving to be a safe and effective for treatment-resistant depression (TRD). However, the likelihood of treatment response remains difficult to predict. It is possible to assess inadequate treatment responses early in treatment courses to predict eventual non-response by course end.

Post-hoc analysis of prospective clinical trial data was conducted (N = 298). Participants were randomized to one of three treatment arms: daily, unilateral 10 Hz rTMS to the left dorsolateral prefrontal cortex or accelerated bilateral theta-burst stimulation (TBS) at either 80 % or 120 % resting motor threshold stimulation intensity. Clinical response was assessed using the Quick Inventory of Depressive Symptomatology (QIDS). Negative predictive values (NPVs) were generated at week 1 using various QIDS percentage improvement cut-offs to predict eventual non-response.

Participants who showed a ≤ 10 % or ≤ 20 % improvement in QIDS score by week 1 had NPVs ranging from 70.0 % to 97.5 %. Higher NPVs were found for participants randomized to low-intensity accelerated TBS than 10 Hz daily rTMS at week 1.

Accelerated TBS and standard rTMS courses featured relatively short courses of 20 sessions. Analyses predict eventual treatment response using only change in QIDS severity without subscale analysis.

Early treatment non-response potentially has predictive utility, including in an accelerated TBS protocol. Further studies should determine whether there is clinical benefit in reviewing and/or adapting treatment protocols in view of these findings.

Cocaine and methamphetamine use disorders (CcUD/MtUD) have serious public health, medical, and psychiatric consequences. Yet, there are no U.S. Food and Drug Administration (FDA) approved treatments available. The STIMULUS study is a multi-site trial, sponsored by the National Drug Abuse Treatment Clinical Trials Network (CTN), that aims to investigate the feasibility and preliminary efficacy of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for moderate to severe CcUD/MtUD.

The study is a double-blind, sham-controlled trial seeking to recruit 160 participants with a current moderate to severe CcUD or MtUD diagnosis, randomized to receive active rTMS (10-Hz stimulation at 120% motor threshold over the left dorsolateral prefrontal cortex) or sham. Feasibility is assessed by a target of at least 20 treatment sessions administered within an 8-week period. Additionally, the study aims to evaluate the efficacy of rTMS in reducing stimulant use and craving, the impact of rTMS on mood, anxiety, sleep, and other measures, and the utility of electroencephalography as a treatment response biomarker.

Studies exploring rTMS for stimulant use disorders remain limited by small sample sizes, as well as great heterogeneity in defined study population, treatment parameters, retention in treatment, and number of sessions. In this paper, we highlight key study design decisions, such as safety, sham procedure, and schedule flexibility.

We hope that the data collected will lay the groundwork for a robust randomized controlled trial of rTMS as a therapeutic intervention for individuals with CcUD/MtUD.

http://www.

gov . Identifier: NCT04907357. TRIAL DATA SET: https://clinicaltrials.gov/study/NCT04907357?tab=table .

Version 7.0, 11/10/2023.

Cognitive control dysregulation is nearly universal across disorders, including major depressive disorder (MDD). Achieving comparable response rates to medication, the transcranial magnetic stimulation (TMS) mechanism and its effect on cognitive control have not been well understood yet. This paper investigates the predictive capability of the clinical response to TMS treatment using 34 cognitive variables measured from TMS treatment of 22 MDD subjects over an eight-week period. We employ a novel brain-inspired computing paradigm, hyperdimensional computing (HDC), to classify the effectiveness of TMS using leave-one-subject-out cross-validation (LOSOCV). Four performance metrics-accuracy, sensitivity, specificity and AUC-are used, with AUC being the primary metric. Experimental results reveal that: i). Although SVM outperforms HDC in terms of accuracy, HDC achieves an AUC of 0.82, surpassing SVM by 0.07. ii). The optimal performance for both classifiers is obtained with feature selection using SelectKBest. iii) Among the top features selected by SelectKBest for the two classifiers, ws_MedRT (median rate for the Websurf task) shows a more distinguishable distribution between clinical responses ("1") and no clinical responses ("0"). In conclusion, these results highlight the potential of HDC for predicting clinical responses to TMS and underscore the importance of feature selection in improving classification performance.

Limited data are available to inform clinicians on how to manage concurrent substance use in the context of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depressive, obsessive-compulsive, psychotic, or trauma-related disorders. The authors convened an international panel of 24 rTMS experts, representative of different geographic regions and subspecialities, and created a consensus guideline for clinicians and researchers on approaches to concurrent substance use in patients receiving rTMS as treatment for primary psychiatric disorders.

A Delphi method survey and expert opinion elicited over consecutive rounds of surveys were used, with feedback and discussion after each round. Recommendation statements were established upon very high (≥80%) agreement.

Three rounds of surveys and feedback were sufficient to reach a consensus for most topics; where consensus could not be reached, the panel discussed limitations in the current evidence base. Informed by a synthesis of the literature and practice-based evidence, the expert panel provides several consensus recommendations on the topics of screening, monitoring, risk assessment, and mitigation associated with various degrees of substance use, and specific considerations for alcohol, cannabis, stimulants, and opioids. Instead of excluding all people who use substances, a nuanced approach should be taken based on an assessment of risk factors for clinical instability and severity of use. The most important safety risk with substance use is the presence of intoxication or withdrawal states, with the most data supporting seizure risk in unstable alcohol or nonmedical stimulant use. Although there is no evidence of reduced rTMS efficacy for a psychiatric disorder in the presence of concurrent substance use, the lack of data in this area warrants caution.

These recommendations can be readily implemented clinically and provide a framework for future research. In patients receiving rTMS for a primary psychiatric disorder, assessment and management of co-occurring substance use is complex, requiring greater attention, standardization, and further study.

Post-traumatic stress disorder (PTSD) is characterized by hypervigilance, intrusive thoughts, negative mood, and avoidant behaviors. Therapies involving mindfulness have been shown to reduce PTSD symptoms and modulate brain function. Pharmacological and brain stimulation interventions are also effective for treating PTSD. Non-invasive repeated transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to regulate mood and improve PTSD symptoms.

This is a retrospective chart analysis of data collected pre-treatment, post-treatment, and at three-month follow-up in a single-site, double-blind, sham-controlled trial of right DLPFC rTMS. 31 participants diagnosed with PTSD were recruited for this pilot study. Over two weeks, 19 participants received ten sessions of either 1 Hz or 10 Hz stimulation, and nine received sham treatment.

Participants in the rTMS group had a significant reduction in total Five Facet Mindfulness Questionnaire (FFMQ) scores from baseline to post-treatment, this difference was no longer observed when a false discovery rate (FDR) correction was applied. However, a significant improvement was observed in the rTMS group from baseline to the three-month follow-up in total FFMQ score and nonreactivity. This change in mindfulness scores suggests a potential delay in onset of benefits.

Based on our preliminary data, rTMS may improve levels of dispositional mindfulness and its specific subcomponents. Future studies could investigate brain stimulation to assess its utility for improving mindfulness and related health outcomes to reduce suffering related to PTSD. Moreover, application of this neurostimulation modality for improving mental illness and well-being more generally merits further exploration.

https://clinicaltrials.gov/study, identifier NCT01806168.

The heterogeneity of depression limits the treatment outcomes of intermittent theta burst stimulation (iTBS) and hinders the identification of predictive factors. This study investigated functional network connectivity and predictors of iTBS treatment outcomes in adolescents and young adults with depression.

This study aimed to identify default mode network (DMN)-based connectivity patterns associated with varying iTBS treatment outcomes in depression.

Data from a randomised controlled trial of iTBS in depression (n=82) were analysed using a data-driven approach to classify homogeneous subgroups based on the DMN. Connectivity subgroups were compared on depressive symptoms and cognitive function at pretreatment and post-treatment. Furthermore, the predictive significance of baseline inflammatory cytokines on post-treatment outcomes was evaluated.

Two distinct subgroups were identified. Subgroup 1 exhibited high heterogeneity and greater centrality in the posterior cingulate cortex and retrosplenial cortex, while subgroup 2 showed more homogeneous connectivity patterns and greater centrality in the temporoparietal junction and posterior inferior parietal lobule. No main effect for subgroup, treatment or subgroup×treatment interaction was revealed in the improvement of depressive symptoms. A significant subgroup×treatment interaction related to symbol coding improvement was detected (F=5.22, p=0.026). Within subgroup 1, the active group showed significantly greater improvement in symbol coding compared with the sham group (t=2.30, p=0.028), while baseline levels of interleukin-6 and C-reactive protein emerged as significant indicators for predicting improvements in symbolic coding (R2=0.35, RMSE (root-mean-square error)=5.72, p=0.013). Subgroup 2 showed no significant findings in terms of cognitive improvement or inflammatory cytokines predictions.

Data-driven network analyses offer valuable insights into iTBS treatment outcomes in depression, providing clues for predicting cognitive improvements from an inflammatory perspective.

ChiCTR2100042346.

Depression has become a global public health problem. In recent years, transcranial magnetic stimulation (TMS) has gained considerable attention as a non-invasive treatment for depression.

To investigate the research hotspots and trends in the field of TMS-based depression treatment from a bibliometric perspective.

Using the Web of Science Core Collection, articles published between 2003 and 2022 on TMS-based depression treatment were retrieved from the science citation index expanded. The publication trends and research hotspots were analyzed using VOSviewer, CiteSpace, and the bibliometric online analysis platform. Regression analysis was performed using Microsoft Excel 2021 to predict publication growth trends.

We identified a total of 702 articles on TMS-based depression treatment with a predominance of clinical studies. Analysis of collaborative networks showed that the United States, the University of Toronto, and Daskalakis ZJ were identified as the most impactful country, institution, and researcher, respectively. In keyword burst analysis, it was found that theta burst stimulation (TBS), functional connectivity, and frequency were the most recent research hotspots.

TMS provides a novel therapeutic option for patients with treatment-resistant depression. Neuroimaging technology enables more precise TMS treatment, while the novel TMS modality, TBS, enhances both therapeutic efficacy and patient experience in TMS-based depression treatment. The integration of neuroimaging techniques with TBS represents a promising research direction for advancing TMS-based depression treatment. This study presents systematic information and recommendations to guide future research on TMS-based depression treatment.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, affecting tens of millions worldwide with projections indicating increasing prevalence in coming decades. Characterized by progressive cognitive decline, AD manifests with varying degrees of executive, language, and visuospatial impairments that worsen over time, eventually leading to severe psychiatric symptoms, mobility difficulties, sleep disturbances, and incontinence. While pharmacological treatments remain the primary intervention approach, their efficacy often diminishes over time and may produce significant adverse effects. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulation technique, has emerged as a promising alternative or complementary therapy. This literature review examines the therapeutic potential and mechanisms of rTMS in Alzheimer's disease. Through electromagnetic induction, rTMS can selectively modulate cortical excitability, with high-frequency stimulation (≥ 5 Hz) enhancing neural excitability and low-frequency stimulation (≤ 1 Hz) producing inhibitory effects. Recent clinical evidence demonstrates that rTMS can significantly improve cognitive function, memory, language abilities, and motor performance in AD patients, particularly when administered with optimized parameters targeting key brain regions, such as the dorsolateral prefrontal cortex. The neurobiological mechanisms underlying these effects include enhanced synaptic plasticity, increased expression of neurotrophic factors, modulation of neurotransmitter systems, and reduction of pathological protein aggregation. Meta-analyses indicate that high-frequency protocols (particularly 20 Hz) delivered over at least 3 weeks with a minimum of 20 sessions produce the most significant cognitive improvements, with effects potentially persisting for months post-treatment. Combined approaches integrating rTMS with cognitive training show particular promise through synergistic enhancement of neuroplasticity. Despite encouraging results, standardization of treatment protocols and larger clinical trials are needed to establish definitive guidelines and determine long-term efficacy. This review synthesizes current evidence supporting rTMS as an effective intervention for alleviating clinical symptoms of Alzheimer's disease while highlighting opportunities for advancing its therapeutic application.

Novel interventions are urgently needed to treat methamphetamine use disorder (MUD), for which there are no FDA-approved treatments. Previous studies in patients with MUD suggest transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L. dlPFC) decreases craving for methamphetamine. Theta burst stimulation (TBS), which includes intermittent TBS and continuous TBS (cTBS), is increasingly being used for substance use disorders, including MUD. Previous reviews of TMS in MUD performed sub-group meta-analyses of studies that delivered TBS in MUD. However, these meta-analyses included studies with overlapping participant cohorts. Given the absence of prior meta-analyses or reviews examining TBS in MUD using unique participant cohorts, we reviewed randomized controlled trials (RCTs) from three databases (PubMed/Medline, EMBASE, Google Scholar) until September 1, 2024, comparing the impact of TBS versus sham TBS on cue-induced methamphetamine cravings in patients with MUD. We performed a meta-analysis with four eligible RCTs that delivered iTBS. Results suggest iTBS was more effective in reducing cue-induced methamphetamine cravings than sham iTBS (standardized mean difference [SMD] in change = 1.04; 95% CI [0.16, 1.92]). Our systematic review included two additional RCTs that did not have sham comparator arms; one of these demonstrated a significant reduction in methamphetamine craving with accelerated iTBS. Future studies should examine if iTBS can impact clinical outcome measures other than craving, such as methamphetamine use, by measuring return to drug use. It is also pertinent to explore accelerated iTBS and cTBS for MUD and study their effects on relevant biomarkers for MUD.

Cognitive impairments are prevalent among stroke patients, impacting independent living. While intermittent theta burst stimulation (iTBS) shows potential for rehabilitation, the efficacy of the commonly-used doses remains unsatisfactory.

To investigate the efficacy, dose-dependent effect, and safety of high-dose iTBS targeting the individualized frontoparietal cognitive network (FCN) for post-stroke cognitive recovery.

In a randomized, sham-controlled, three-arm trial, patients with post-stroke cognitive impairment (PSCI) received 15 days of high-dose (3600 pulses/day), standard low-dose (1200 pulses/day) as an active control, or sham iTBS targeting the individualized FCN, alongside cognitive training. Primary outcome measured changes in global cognition via the Montreal Cognitive Assessment (MoCA). Secondary measures included MoCA response rates and score changes in the Wechsler Memory Scale, Wechsler Adult Intelligence Scale, and Mini-Mental State Examination.

Of forty-five randomized participants, forty-one (8 women; mean [SD] age, 58.63 [8.64] years) were analyzed. Personalized targeting improved focality by 33.0 % over the standard F3 target in E-field analysis. Both high-dose and standard low-dose groups showed significant improvements in MoCA. Importantly, the high-dose group demonstrated superior cognitive recovery over both the active control group (estimated difference = 2.50, p = 0.0339, 95 % CI = 0.15-4.84) and the sham control group (estimated difference = 4.29, p = 0.0001, 95 % CI = 1.99-6.60), indicating a superior effect of high-dose stimulation for cognitive recovery. Similar high-dose and dose-dependent effects were observed in other secondary outcomes, suggesting consistent effects on the memory, intelligence, and mental state. No serious adverse events occurred.

This study highlights the efficacy and safety of high-dose iTBS targeting the individualized FCN for post-stroke cognitive recovery.

The noninvasive brain and nerve stimulation (NIBNS) treatments had been widely applied in numerous psychiatric diseases. They exerted preferable efficacy and had been considered as an alternative or add-on treatment to the traditional pharmacotherapy. However, the risk of complication of seizure had seized the clinicians so that they feared about this potential complication. Actually, the NIBNS techniques have emerged as an alternative adjunctive treatment method for patients with epilepsy. However, the results of randomized controlled trials (RCTs) investigating the ability of NIBNS to reduce the frequency of seizures have been inconclusive. The aim of the current network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBNS techniques for reducing the frequency of seizures in patients with epilepsy. This frequentist model-based NMA included RCTs of NIBNS techniques for patients with epilepsy. The primary outcomes were seizure frequency change and acceptability (i.e., dropout rate). This NMA of 20 RCTs indicated that only 2-mA cathodal short-duration transcranial direct current stimulation (hc-sd-c-tDCS) was associated with significantly greater reduction in seizure frequency and significantly greater improvement in quality of life than the sham/control. Further, none of the investigated NIBNS techniques had significantly increased seizure frequency compared with the sham/control. In addition, all the investigated NIBNS techniques were associated with similar acceptability with the sham/control. Our results indicated that none of the investigated NIBNS techniques was associated with an increased risk of epileptic seizure.

Repetitive Transcranial Magnetic Stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) are non-invasive treatments for major depressive disorder (MDD). While effective, variability in outcomes necessitates identifying predictors of therapeutic response. This study examined whether motor threshold (MT), percentage of motor threshold (%MT), and treatment intensity could predict clinical outcomes in MDD patients undergoing rTMS and iTBS.

Adult MDD patients treated with NeuroStar rTMS or iTBS at Mayo Clinic from February 2016 to April 2024 were included. MT, %MT, and treatment intensity were recorded. Clinical outcomes were assessed via Patient Health Questionnaire-9 (PHQ-9) score changes, response (PHQ-9 change ≥50 %), remission (PHQ-9 < 5), and a patient-reported outcome (PRO) on treatment helpfulness. Linear and logistic regression models were used to assess predictors of clinical outcomes.

Among 149 patients analyzed (mean age 45.7, 67.8 % female), response rate was 43.0 % and remission rate was 16.8 %. MT and %MT did not significantly correlate with clinical outcomes. Treatment intensity and TMS type did not predict PHQ-9 score changes. Higher treatment intensity was associated with decreased odds of positive PRO responses. Linear regression showed that age and gender significantly predicted PHQ-9 score changes, with older patients and females showing greater improvement. MT was significantly lower in men and with iTBS compared to rTMS.

MT, %MT, and treatment intensity did not reliably predict outcomes. Higher intensity was linked to reduced patient-reported helpfulness, suggesting that patient comfort is crucial. iTBS's lower MT may benefit those needing less stimulation. Future research should identify better predictors to improve TMS outcomes.

The purpose of this study was to systematically evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) therapy on sleep quality in patients with more than mild depressive mood.

Randomized controlled trials in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and ScienceDirect on rTMS to improve sleep quality in patients with more than mild depressive mood up to September 2023 were searched. A meta-analysis was performed using RevMan 5.4 and Stata 17.0 software.

A total of 11 studies, which involved 548 patients, were included. After rTMS treatment, the effect on sleep quality improvement in patients with more than mild depressive mood was better in the experimental group than in the control group [I 2 = 53%, mean difference (MD) = -2.27, 95%CI = -2.97 to -1.57, p < 0.00001]. The results of the subgroup analyses showed that, in terms of stimulation frequency, compared with the 5-Hz and 10-Hz groups, the treatment effect of the 1-Hz group was better (I 2 = 32%, MD = -2.69, 95%CI = -3.78 to -1.60, p < 0.00001). In terms of treatment duration, compared with the 2-week and 4-week groups, the group with more than 4 weeks of treatment had better treatment outcomes (I 2 = 0%, MD = -2.81, 95%CI = -3.22 to -2.40, p < 0.00001). In terms of whether combination therapy was used or not, compared with the combination therapy group (I 2 = 29%, MD = -1.39, 95%CI = -2.30 to -0.48, p = 0.003), the non-combination therapy group had a better treatment effect (I 2 = 0%, MD = -2.93, 95%CI = -3.36 to -2.50, p < 0.00001).

rTMS significantly improves sleep quality in patients with more than mild depression. Subgroup analyses showed that the group using the 1-Hz stimulation frequency, the group with more than 4 weeks of treatment time, and the group with rTMS alone had better efficacy in treating the sleep quality of patients with more than mild depressive mood using rTMS, with the use of combination treatment or not being the main source of heterogeneity.

https://www.crd.york.ac.uk/prospero/, identifier CRD42023467971.

This study compares the safety and effectiveness of theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) for treating treatment-resistant depression (TRD).

We reviewed randomized controlled trials (RCTs) that evaluated rTMS and TBS in managing TRD. Searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published up to July 31, 2024. Data from these studies were analyzed using statistical software.

Five RCTs involving 1,196 patients were included, with 553 receiving rTMS and 663 receiving TBS. The analysis found no significant differences between rTMS and TBS in reducing depression [SMD = -0.07, 95% CI (-0.19, 0.04)] or anxiety [SMD = -0.02, 95% CI (-0.15, 0.11)], nor in side effects like headaches [OR = 1.00, 95% CI (0.72, 1.40)], nausea [OR = 1.42, 95% CI (0.79, 2.54)], or fatigue [OR = 0.87, 95% CI (0.46, 1.64)].

Both rTMS and TBS are similarly effective in reducing depression and anxiety symptoms, with comparable side effect profiles. However, TBS is more time-efficient, with sessions lasting only 192 seconds, making it a cost-effective option for patients. These findings support TBS as a practical treatment choice for TRD.

This article updates the prior 2018 consensus statement by the National Network of Depression Centers (NNDC) on the use of transcranial magnetic stimulation (TMS) in the treatment of depression, incorporating recent research and clinical developments. Publications on TMS and depression between September 2016 and April 2024 were identified using methods informed by PRISMA guidelines. The NNDC Neuromodulation Work Group met monthly between October 2022 and April 2024 to define important clinical topics and review pertinent literature. A modified Delphi method was used to achieve consensus. 2,396 abstracts and manuscripts met inclusion criteria for review. The work group generated consensus statements which include an updated narrative review of TMS safety, efficacy, and clinical features of use for depression. Considerations related to training, roles/responsibilities of providers, and documentation are also discussed. TMS continues to demonstrate broad evidence for safety and efficacy in treating depression. Newer forms of TMS are faster and potentially more effective than conventional repetitive TMS. Further exploration of targeting methods, use in special populations, and accelerated protocols is encouraged. This article provides an updated overview of topics relevant to the administration of TMS for depression and summarizes expert, consensus opinion on the practice of TMS in the United States.

To compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression.

42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05.

The absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines.

There was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.

Major depressive disorder (MDD) is prevalent among older patients and is frequently associated with cognitive decline and a reduced quality of life. Non-invasive brain stimulation (NIBS) techniques show promise for treating MDD, but their comparative efficacy and safety older populations remain unclear. This study aimed to compare the efficacy and cognitive effects of various NIBS techniques in treating MDD in older patients.

We searched the PubMed, EMBASE, Cochrane Library, and Web of Science core databases from inception to March 2024. Seventeen randomized controlled trials (RCTs) were included.

Surfaces under the cumulative ranking curve (SUCRA) values were used to rank the interventions. The SUCRA rankings for the Hamilton Depression Rating Scale (HDRS) outcomes indicated that repetitive transcranial magnetic stimulation (rTMS) (89.0 %) had the highest efficacy, followed by transcranial direct current stimulation (tDCS) (68.7 %). rTMS demonstrated significantly superior efficacy compared with bilateral electroconvulsive therapy (BL ECT) and right unilateral electroconvulsive therapy (RUL ECT). Theta burst stimulation (TBS) had the highest response rate (69.6 %), followed by rTMS (61.8 %). Based on the Mini-Mental State Examination, rTMS (86.4 %) ranked the highest, with RUL ECT showing significantly better outcomes than BL ECT.

NIBS, particularly rTMS and TBS, may offer effective treatment options for older patients with MDD. Further research with larger sample sizes and longer follow-up periods is required to validate these findings and inform clinical practice.

Neuromodulation stands as a cutting-edge approach in the fields of neuroscience and therapeutic intervention typically involving the regulation of neural activity through physical and chemical stimuli. The purpose of this review is to provide an overview and evaluation of different neuromodulation techniques, anticipating a clearer understanding of the future developmental trajectories and the challenges faced within the domain of neuromodulation that can be achieved. This review categorizes neuromodulation techniques into genetic neuromodulation methods (including optogenetics, chemogenetics, sonogenetics, and magnetogenetics) and non-genetic neuromodulation methods (including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, transcranial ultrasound stimulation, photobiomodulation therapy, infrared neuromodulation, electromagnetic stimulation, sensory stimulation therapy, and multi-physical-factor stimulation techniques). By systematically evaluating the principles, mechanisms, advantages, limitations, and efficacy in modulating neuronal activity and the potential applications in interventions of neurological disorders of these neuromodulation techniques, a comprehensive picture is gradually emerging regarding the advantages and challenges of neuromodulation techniques, their developmental trajectory, and their potential clinical applications. This review highlights significant advancements in applying these techniques to treat neurological and psychiatric disorders. Genetic methods, such as sonogenetics and magnetogenetics, have demonstrated high specificity and temporal precision in targeting neuronal populations, while non-genetic methods, such as transcranial magnetic stimulation and photobiomodulation therapy, offer noninvasive and versatile clinical intervention options. The transformative potential of these neuromodulation techniques in neuroscience research and clinical practice is underscored, emphasizing the need for integration and innovation in technologies, the optimization of delivery methods, the improvement of mediums, and the evaluation of toxicity to fully harness their therapeutic potential.

Dialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating borderline personality disorder (BPD). Impulsivity and impaired decision-making are prominent features of BPD, and therapeutic interventions targeting these symptoms could lead to significant improvements.

We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that targets the left dorsolateral prefrontal cortex, would enhance the therapeutic effects of DBT, leading to greater improvements in impulsivity and decision-making compared with sham stimulation.

We performed a single-blind, randomized, sham-controlled pilot study to evaluate the efficacy of iTBS as an add-on to an 8-week DBT program for BPD in a routine inpatient setting. A total of 53 BPD patients were randomly assigned to receive either iTBS (n = 25) or sham stimulation (n = 28) during weeks 4 to 8 of DBT, and 36 patients met the inclusion criteria for the present analysis (≥ 16 of 20 iTBS/sham sessions and assessment of delay discounting). The study endpoints were the Barratt Impulsiveness Scale-15 for impulsivity and the Monetary Choice Questionnaire for decision-making/delay discounting.

A mixed model repeated measures analysis with a 2 × 2 factorial between-subjects design showed a significant overall improvement over time in impulsivity but not in decision-making/delay discounting. No significant differences were found between iTBS and sham, although post hoc tests revealed significant changes in impulsivity in the iTBS group (meandiff = -4.7, p = .001, Cohen's d = 0.68) but not in the sham group (meandiff = -2.1, p = .077, d = 0.31).

iTBS may offer long-term benefits as an add-on treatment to DBT for impulsivity in BPD, suggesting the need for further investigation in larger-scale studies.

Registered at drks.de (no. DRKS00020413) on January 13, 2020.

Transcranial magnetic stimulation (TMS) is a safe non-invasive treatment technique. We systematically reviewed randomised controlled trials (RCTs) applying TMS in obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) to analyse its therapeutic benefits and explore the relationship between cortical target and psychopathophysiology. We included 47 randomised controlled trials (35 for OCD) and found a 22.7 % symptom improvement for OCD and 29.4 % for PTSD. Eight cortical targets were investigated for OCD and four for PTSD, yielding similar results. Bilateral dlPFC-TMS exhibited the greatest symptom change (32.3 % for OCD, N = 4 studies; 35.7 % for PTSD, N = 1 studies), followed by right dlPFC-TMS (24.4 % for OCD, N = 8; 26.7 % for PTSD, N = 10), and left dlPFC-TMS (22.9 % for OCD, N = 6; 23.1 % for PTSD, N = 1). mPFC-TMS showed promising results, although evidence is limited (N = 2 studies each for OCD and PTSD) and findings for PTSD were conflicting. Despite clinical improvement, reviewed reports lacked a consistent and solid rationale for cortical target selection, revealing a gap in TMS research that complicates the interpretation of findings and hinders TMS development and optimisation. Future research should adopt a hypothesis-driven approach rather than relying solely on correlations from imaging studies, integrating neurobiological processes with affective, behavioural, and cognitive states, thereby doing justice to the complexity of human experience and mental illness.

The position and orientation of transcranial magnetic stimulation (TMS) coil, which we collectively refer to as coil placement, significantly affect both the assessment and modulation of cortical excitability. TMS electric field (E-field) simulation can be used to identify optimal coil placement. However, the present E-field simulation required a laborious segmentation and meshing procedure to determine optimal coil placement. We intended to create a framework that would enable us to offer optimal coil placement without requiring the segmentation and meshing procedure. We constructed the stimulation effects map (SEM) framework using the CASIA dataset for optimal coil placement. We used leave-one-subject-out cross-validation to evaluate the consistency of the optimal coil placement and the target regions determined by SEM for the 74 target ROIs in MRI data from the CASIA, HCP15 and HCP100 datasets. Additionally, we contrasted the E-norms determined by optimal coil placements using SEM and auxiliary dipole method (ADM) based on the DP and CASIA II datasets. We provided optimal coil placement in 'head-anatomy-based' (HAC) polar coordinates and MNI coordinates for the target region. The results also demonstrated the consistency of the SEM framework for the 74 target ROIs. The normal E-field determined by SEM was more significant than the value received by ADM. We created the SEM framework using the CASIA database to determine optimal coil placement without segmentation or meshing. We provided optimal coil placement in HAC and MNI coordinates for the target region. The validation of several target ROIs from various datasets demonstrated the consistency of the SEM approach. By streamlining the process of finding optimal coil placement, we intended to make TMS assessment and therapy more convenient.

Anxiety disorders are among the most common mental disorders. Treatment guidelines recommend pharmacotherapy and cognitive behavioral therapy as standard treatment. Although cognitive behavioral therapy is an effective therapeutic approach, not all patients benefit sufficiently from it. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, have been investigated as promising adjuncts in the treatment of affective disorders. The aim of this study is to investigate whether a combination of intermittent theta burst stimulation (iTBS) and virtual reality exposure therapy leads to a significantly greater reduction in acrophobia than virtual reality exposure with sham stimulation. In this randomized double-blind placebo-controlled study, 43 participants with acrophobia received verum or sham iTBS over the left dorsolateral prefrontal cortex prior to two sessions of virtual reality exposure therapy. Stimulation of the left dorsolateral prefrontal cortex with iTBS was motivated by an experimental study showing a positive effect on extinction memory retention. Acrophobic symptoms were assessed using questionnaires and two behavioral approach tasks one week before, after treatment and six months after the second diagnostic session. The results showed that two sessions of virtual reality exposure therapy led to a significant reduction in acrophobic symptoms, with an overall remission rate of 79 %. However, there was no additional effect of iTBS of the left dorsolateral prefrontal cortex on the therapeutic effects. Further research is needed to determine how exactly a combination of transcranial magnetic stimulation and exposure therapy should be designed to enhance efficacy.

Bilateral repetitive transcranial magnetic stimulation (BL-rTMS) over the dorsolateral prefrontal cortex is effective for treatment-resistant depression (TRD). Owing to a shorter treatment time, bilateral theta burst stimulation (BL-TBS) can be more efficient protocol. The non-inferiority of BL-TBS to BL-rTMS was established in late-life TRD; however, this has not been determined in adults of other age groups. Therefore, we investigated the non-inferiority in efficacy of BL-TBS versus BL-rTMS for TRD across a wide range of ages in a randomized, single-blind, multicenter trial.

The study included 180 participants with major depressive disorder (moderate or greater severity) who were unresponsive to at least one antidepressant treatment between September 2018 and July 2022. Following venlafaxine treatment, patients were randomly assigned to BL-rTMS or BL-TBS (1:1 ratio). The primary outcome was baseline-adjusted Montgomery-Åsberg Depression Rating Scale scores at 6 weeks. The non-inferiority margin of -3.86 was compared against the baseline-adjusted difference. Secondary outcomes included other depression rating scales.

Seventy-seven patients were randomly assigned to BL-rTMS and 81 to BL-TBS, of whom 73 and 76 were assessed for the primary outcome, respectively. There was a -2.44 point difference, favoring BL-rTMS (one-tailed lower 95 % CI = -4.19, p = 0.091 for non-inferiority), and non-inferiority of BL-TBS was not established. However, non-inferiority was observed for secondary outcomes. The all-cause dropout rates and number of adverse effects were similar between them.

Our study could not establish the non-inferiority of BL-TBS compared to BL-rTMS in terms of efficacy for patients with TRD across the adult lifespan.

Major depressive disorder (MDD) is a common psychiatric condition that causes considerable morbidity and disability. MDD is characterized by recurrent depressive episodes that can result in loss of productivity, job insecurity, social isolation, and suicidality. Primary care providers frequently provide the initial management of MDD; however, some patients do not respond to first- or second-line treatments, a condition called treatment-resistant depression (TRD). Understanding how to accurately diagnose and manage TRD is important for clinicians.

Repetitive TMS (rTMS) has been demonstrated to be an effective treatment of several neuropsychiatric disorders. Its safety and efficacy are well established, and multiple rTMS devices have been approved by both Conformitè Europëenne Mark and U.S. Food and Drug Administration. We aimed to survey TMS practice in Psychiatry in the Kingdom of Denmark and compare it with the international state of the art.

A survey of rTMS clinical practice in 2023 was sent to all general adult psychiatry departments practicing TMS in the Danish Realm (Denmark = 10, Faroe Islands = 0, Greenland = 0).

Response rate was 100%. rTMS was available in 37% of psychiatric departments and 3 out of 5 Danish Regions. Admission criteria required a diagnosis of unipolar depression with a degree of treatment-resistance or unacceptable side-effects to antidepressant treatment. Common contraindications included: cochlear implants (100%), pacemaker and neurostimulators (80%), other ferromagnetic/implanted devices in head, neck, or thorax (70%), active substance misuse (60%), and electrolytic disturbances (50%). Three rTMS protocols were identified: 10 Hz rTMS delivered over the L-DLPFC, iTBS delivered over the L-DLPFC and 1 Hz rTMS delivered over the right-DLPFC. 383 patients were treated with TMS.

rTMS is unequally available in the public healthcare of the Kingdom of Denmark. Existing strategies for solving inequalities could address such issues. Unipolar depression was the only psychiatric disorder treated with rTMS in 2023. rTMS practice in the Danish Realm considers the use of evidence-based protocols and is consistent with recommendations from international expert guidelines.

Postoperative delirium (POD) is a serious complication in elderly patients after major surgery, associated with high morbidity and mortality. Treatment and prevention methods are limited. Repetitive transcranial magnetic stimulation (rTMS) shows potential in enhancing cognitive function and improving consciousness.

To evaluate whether early postoperative rTMS has a protective effect against POD and to explore its potential mechanisms.

Patients aged 60 years or older, scheduled for major abdominal surgery, were randomly assigned to receive rTMS at 100 % RMT, 10 Hz, with 2000 pulses targeting the DLPFC after extubation in PACU, either as active rTMS(n = 61) or sham rTMS (n = 61). The primary outcome was the incidence of POD during the first 3 postoperative days.

In the modified intention-to-treat analysis of 122 patients (mean [SD] age, 70.2 [4.1] years; 53.3 % women), POD incidence was lower in the rTMS group (11.5 %) compared to the sham rTMS group (29.5 %) (relative risk, .39; 95 % CI, .18 to .86; P = .01). rTMS patients had higher BDNF (8.47 [2.68] vs. 5.76 [1.42] ng/mL; P < .001) and lower NfL (.05 [.04] vs. .06 [.04] ng/mL; P = .02) levels. Mediation analysis suggests that rTMS may reduce POD by increasing brain-derived neurotrophic factor (z = -3.72, P < .001) rather than decreasing neurofilament light (z = 1.92, P = .06).

Immediate postoperative rTMS can reduce the incidence of POD in elderly patients undergoing major abdominal surgery, probably by upregulating brain-derived neurotrophic factor levels.

Catatonia is a rare but life-threatening condition characterized by a constellation of psychomotor disturbances. The most widely used treatments of catatonia include benzodiazepines and electroconvulsive therapy. Despite the widespread use of benzodiazepines and the high response rate of catatonia to ECT, there are instances where catatonia does not respond to first-line treatments. This study aimed to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in managing catatonia.

A systematic literature search was conducted on the following databases: Medline, PubMed, Cochrane Library, Embase, PsycINFO and ClinicalTrials.gov for registered but not yet published studies.

Out of 244 initially identified articles, there remained eight case reports and 1 case series eligible after screening. Of the twelve total cases, nine showed clinical improvement. However, there was significant heterogeneity in the complexity of the clinical situation, the severity of clinical features of catatonia, underlying causes, and rTMS treatment protocols between studies.

The results of this study are inconclusive. However, rTMS might be trialed for the management of catatonia when first-line treatment options fail, are unavailable, or need to be used with caution. Our review incorporating the most up to date evidence highlights the need for more extensive, standardized, randomized clinical trials to investigate the efficacy of rTMS for treating catatonia.

Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in enhancing motor recovery after stroke, but nuances regarding its use, such as the impact of the type and site of stimulation, are not yet established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) with low risk of bias to investigate the effect of rTMS on motor recovery after both ischemic and hemorrhagic stroke.

Three databases were searched systematically for all RCTs reporting comparisons between rTMS (including theta-burst stimulation) and either no stimulation or sham stimulation up to August 19, 2022. The primary outcome measure was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE). Secondary outcome measures comprised the Action Research Arm Test, Box and Block Test, Modified Ashworth Scale for the wrist, and modified Rankin Scale (mRS).

A total of 37 articles reporting 48 unique comparisons were included. Pooled mean FMA-UE scores were significantly higher in the experimental group than the control group after intervention (MD = 5.4 [MD = 10.7 after correction of potential publication bias], p < 0.001) and at the last follow-up (MD = 5.2, p = 0.031). On subgroup analysis, the improvements in FMA-UE scores, both after intervention and at the last follow-up, were significant in the acute/subacute stage of stroke (within six months) and for patients with more severe baseline motor impairment. Both contralesional and ipsilesional stimulation yielded significant improvements in FMA-UE at the first assessment after rTMS but not at the last follow-up, while the improvements from bilateral rTMS only achieved statistical significance at the last follow-up. Among the secondary outcome measures, only mRS was significantly improved in the rTMS group after intervention (MD = -0.5, p = 0.013) and at the last follow-up (MD = -0.9, p = 0.001).

Current literature supports the use of rTMS for motor recovery after stroke, especially when done within six months and for patients with more severe stroke at baseline. Future studies with larger sample sizes may be helpful in clarifying the potential of rTMS in poststroke rehabilitation.