Transcranial Magnetic Stimulation Treatment Research Articles

A Systematic Review Assessing Patient-Related Predictors of Response to Transcranial Magnetic Stimulation in Major Depressive Disorder.

The safety and efficacy of transcranial magnetic stimulation (TMS) in the acute treatment of major depressive disorder (MDD) is well established. However, it is not well understood which patient-related factors are associated with a more robust antidepressant response. Identifying predictive factors for therapeutic response to TMS treatment in depression will guide clinicians in patient selection. By systematic review of clinical trial data, the current study aims to identify and analyze reported patient-specific predictors of response to an acute course of TMS treatment for MDD. PubMed was searched for randomized controlled trials of TMS for patients with depression. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. TMS data were available from 375 studies, 18 of which were included in this review. Treatment response is inversely associated with treatment refractoriness and age. Inadequate sample size and large heterogeneity in study parameters among clinical trials limit any strong conclusions from being drawn; nonetheless, despite these limitations, there is mounting evidence, which points to age and treatment refractoriness as candidate variables for predicting clinical outcome. Implications of these findings for treatment of MDD are discussed.

Accelerated repetitive transcranial magnetic stimulation (ATMS) vs standard repetitive transcranial magnetic stimulation (RTMS) in the treatment of major depressive episodes. preliminary data of a randomized, single-blind, controlled trial

IntroductionMajor Depressive Disorder is a frequent and disabling condition. More than 20% of patients do not respond to pharmacotherapy alone, so there is the need to find alternative strategies in order to potentiate the drugs. Therapeutic alternatives include repetitive Transcranial Magnetic Stimulation (rTMS), which has shown an antidepressant effect in the last decades.ObjectivesComparison of the efficacy of accelerated repetitive Transcranial Magnetic Stimulation (aTMS) treatment (4 sessions/day for 5 days) with the standard rTMS protocol treatment (1 session/day for 4 weeks), using the FDA-approved parameters.Methods33 patients affected by Major Depressive Episodes treated with either Fluvoxamine or Venlafaxine were enrolled. Patients were randomly assigned to the two protocol groups: standard rTMS protocol (15 patients) and aTMS protocol (18 patients). In the standard protocol, patients received 1 rTMS session/day for 4 weeks, while in the aTMS protocol they received 4 rTMS sessions/day for 5 days. Symptomatological improvement was evaluated through MADRS, BDI-II and SSI rating scales administered on day: 0, 1, 2, 3, 4, 5, 14, 21, 28, 56. The study is single-blind, since the clinical rater was unaware of the treatment protocol group. Response and remission rates were calculated, defined respectively as a reduction ≥50% in the MADRS score and a MADRS score <10.ResultsThe analysis was carried out on 32 patients (18 in the aTMS group and 14 in the rTMS group). ANOVA for repeated measures shows a statistically significant difference in the MADRS scores on day 5 (p=0.001) and on day 56 (p=0.037). Regarding the BDI-II evaluation, the differences were not fully statistically significant on day 5 and not significant on day 56. No statistically significant differences between the two protocols were observed in the SSI assessment. The aTMS and rTMS response rates were respectively 84.6% vs 45.5% on day 28 (p=0.043) and 92.3% vs 45.5% on day 56 (p=0.012). The aTMS and rTMS group remission rates were respectively 76.9% vs 18.2% on day 28 (p=0.004) and 69.2% vs 36.4% on day 56 (p=0.107). Concerning side effects, no statistically significant differences were observed between the two groups.ConclusionsTreatment with aTMS seems faster and more effective than treatment with standard rTMS in improving the clinical condition in patients with Major Depressive Episodes, allowing to treat patients in just 5 days instead of 4-6 weeks, without impacting on side effects and tolerability.Disclosure of InterestNone Declared

Functional Activity in the Effect of Transcranial Magnetic Stimulation Therapy for Patients with Depression: A Meta-Analysis.

Depression is a long-lasting mental disorder that affects more than 264 million people worldwide. Transcranial magnetic stimulation (TMS) can be a safe and effective choice for the treatment of depression. Functional neuroimaging provides unique insights into the neuropsychiatric effects of antidepressant TMS. In this meta-analysis, we aimed to assess the functional activity of brain regions caused by TMS for depression. A literature search was conducted from inception to 5 January 2022. Studies were then selected according to predetermined inclusion and exclusion criteria. Activation likelihood estimation was applied to analyze functional activation. Five articles were ultimately included after selection. The main analysis results indicated that TMS treatment for depression can alter the activity in the right precentral gyrus, right posterior cingulate, left inferior frontal gyrus and left middle frontal gyrus. In resting-state studies, increased activation was shown in the right precentral gyrus, right posterior cingulate, left inferior frontal gyrus and left superior frontal gyrus associated with TMS treatment. In task-related studies, clusters in the right middle frontal gyrus, left sub-gyrus, left middle frontal gyrus and left posterior cingulate were hyperactivated post-treatment. Our study offers an overview of brain activity changes in patients with depression after TMS treatment.

The relationship of neuroanatomy on resting motor threshold and induced electric field strength on treatment outcomes in mild to moderate traumatic brain injury patients during transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive treatment protocol for treating several psychiatric conditions, including depression, migraine, smoking cessation, and obsessive-compulsive disorder. Past research suggests that TMS treatment outcomes vary based on neuroanatomy, functional connectivity, and tractography-based structural connectivity. In a previous study, 26 mild to moderate traumatic brain injury (mTBI) patients underwent repetitive transcranial magnetic stimulation (rTMS) and showed improvements in depression, post-concussive symptoms, and sleep dysfunction. The present study was a secondary analysis of that data. Anatomically accurate head models were derived from magnetic resonance imaging (MRI), and finite element analysis simulations were performed to mimic empirical data collection. This allowed for examination of the roles that age, brain scalp distance (BSD), gray matter volume (GMV), site-specific electrical field strength (EFS), and depolarized gray matter volume (DGMV) had on resting motor threshold (RMT) at the precentral gyrus (PreCG). We also investigated how EFS simulated at the dorsolateral prefrontal cortex (DLPFC) and RMT influenced rTMS treatment outcomes. Linear regression showed BSD was associated with EFS, RMT, and DGMV supporting efforts to derive accurate parameters from MRI-based modeling. Furthermore, linear mixed effects modeling showed RMT was associated with EFS and DGMV at the PreCG when age and individual neuroanatomy was accounted for suggesting MRI based anatomy and simulated EFS potentially determine TMS dosage. We did not observe any significant relationship between any of the measures from this study on empirically collected rTMS outcomes in mTBI suggesting further investigations into the mechanisms behind these outcomes are needed.

The Anxiolytic and Antidepressant Effects of Transcranial Magnetic Stimulation in Patients With Anxious Depression.

Objective: To determine the extent that treatment with transcranial magnetic stimulation (TMS) in diverse clinical settings has anxiolytic and antidepressant effects in patients with major depressive disorder (MDD) and moderate-to-severe anxiety symptoms and to contrast anxious and nonanxious depression subgroups in antidepressant effects.Methods: Within the NeuroStar Advanced Therapy System Clinical Outcomes Registry, 1,820 patients were identified with a diagnosis of MDD (using ICD-9, ICD-10, or DSM-IV) who completed the Patient Health Questionnaire-9 (PHQ-9) and Global Anxiety Disoder-7 scale (GAD-7) at baseline and following at least 1 TMS treatment between May 2016 and January 2021. Anxious depression was defined as a baseline GAD-7 score of 10 or greater (n = 1,514) and nonanxious depression by GAD-7 scores below this threshold (n = 306). Intent-to-treat and Completer samples were defined for patients treated with any TMS protocol and for the subgroup treated only with high-frequency left dorsolateral prefrontal cortex stimulation.Results: Patients with anxious depression showed clinically meaningful anxiolytic and antidepressant effects, averaging approximately 50% or greater reductions in both GAD-7 and PHQ-9 scores following TMS in all samples. The anxious and nonanxious depression groups had equivalent absolute improvement in PHQ-9 scores (P values ≥ .29). However, the anxious group had higher scores both at baseline and following TMS resulting in significantly lower categorical rates of response (P values < .02) and remission (P values < .001) in depressive symptoms. Among those with anxious depression, the change in anxiety and depression symptoms strongly covaried (r1512 = 0.75, P < .001).Conclusions: Routine TMS delivered in diverse clinical settings results in marked anxiolytic and antidepressant effects in patients with anxious depression. The extent of improvement in anxiety and depression symptoms strongly covaries.

Repetitive transcranial magnetic stimulation for treatment of limb spasticity following multiple sclerosis: a systematic review and meta-analysis.

Pilot trials have suggested that repetitive transcranial magnetic stimulation (rTMS) may reduce limb spasticity in multiple sclerosis (MS). We carried out the current meta-analysis to synthesize currently available evidence regarding such correlation. Up to November 2022, five international electronic databases (Cochrane CENTRAL, PubMed, Embase, Web of Science, and CINAHL) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched to identify randomized trials comparing active rTMS and sham stimulation in patients with MS-related spasticity. Two reviewers independently selected studies and extracted data on study design, quality, clinical outcomes, and time points measured. The primary outcome was clinical spasticity relief after intervention. Secondary outcomes included spasticity at the follow-up visit 2 weeks later and post-treatment fatigue. Of 831 titles found, we included 8 studies (181 participants) in the quantitative analysis. Pooled analyses showed that rTMS therapy was associated with significant spasticity relief in the early post-intervention period [standardized mean differences (SMD): -0.67; 95%CI: -1.12 to -0.21], but there was insufficient evidence for rTMS in reducing spasticity at the follow-up visit 2 weeks later (SMD: -0.17; 95%CI: -0.52 to 0.17) and fatigue (SMD: -0.26; 95%CI: -0.84 to 0.31). This evidence supports the recommendations to treat MS-related spasticity with rTMS, but underlines the need for further large randomized trials.

Accelerated intermittent theta burst transcranial magnetic stimulation is a safe and efficacious treatment for adolescents with depressive symptoms

Abstract Background: Intermittent theta burst stimulation (iTBS) has been shown to be a safe and effective therapy for depression in adult populations and more recently, newer protocols of accelerated transcranial magnetic stimulation (TMS) have become popularized due to the fast-acting effects. Previous literature has shown that iTBS in adolescents is safe and that TMS may be more effective in younger individuals, but it has yet to be explored in great detail with accelerated protocols. Methods: This case series describes three patients seen in the context of an outpatient clinic setting at Acacia Mental Health. The patients were treated for depressive symptoms which were confirmed by a staff psychiatrist. Self-reported mood surveys as assessed by the patient health questionnaire-9 (PHQ-9), were administered pre-treatment and post-treatment. The accelerated TMS treatment protocol administered to these patients varied in the brain region(s) targeted, TMS machine output intensity, protocol laterality, number of sessions per day, and total number of sessions. The TMS treatments were delivered via a MagVenture MagPro R30 system (MagVenture A/S, Denmark) equipped with a MagVenture Cool-B65 A/P coil. Results: All three cases were prescribed distinct accelerated protocols; two achieved self-reported remission and one achieved response as measured by the PHQ-9. All patients tolerated accelerated iTBS sessions without significant adverse events, demonstrating that this is a safe and effective treatment for adolescents with MDD. Conclusion: In these adolescent patients, accelerated TMS protocols were tolerated and showed meaningful clinical effects. These cases support rationale for future clinical applications of accelerated TMS in adolescent populations. Future studies should examine larger cohorts to gain a deeper understanding of accelerated TMS safety and efficacy in adolescents. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Transcranial Magnetic Stimulation, Theta Burst, Adolescence, Depression

Repetitive transcranial magnetic stimulation for chemotherapy-induced peripheral neuropathy in multiple myeloma: A pilot study

Objective: Chemotherapy-induced peripheral neuropathy is one of the major toxicities in multiple myeloma patients, often resulting in dose reductions or treatment interruptions. Repetitive transcranial magnetic stimulation is a safe non-invasive neuromodulation therapy with potential benefits for chemotherapy-induced peripheral neuropathy. The objective of this study was to investigate the efficacy of repetitive transcranial magnetic stimulation treatment on chemotherapy-induced peripheral neuropathy in multiple myeloma patients. Materials and methods: We screened 30 multiple myeloma patients with chemotherapy-induced peripheral neuropathy who underwent repetitive transcranial magnetic stimulation treatment in this study. Prior to and following repetitive transcranial magnetic stimulation treatment, patients were assessed with nerve conduction velocity, visual analog scale and the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item scale (EORTC QLQ-CIPN20). Categorical and continuous variables were analyzed using Fisher’s exact test and Mann-Whitney U test respectively. A p-value &lt; 0.05 (2-tailed) was considered statistically significant. Results: Following repetitive transcranial magnetic stimulation treatment, 24/30 (80.0%) patients reported a reduction in chemotherapy-induced peripheral neuropathy symptoms. Meanwhile, all 15 patients with grade 2 chemotherapy-induced peripheral neuropathy experienced improvements about themselves, compared to 8/10 patient with grade 3 chemotherapy-induced peripheral neuropathy and 1/5 with grade 4 chemotherapy-induced peripheral neuropathy. Visual analog scale scores decreased after repetitive transcranial magnetic stimulation treatment (5.40 ± 1.94 vs 3.10 ± 1.60, p &lt; 0.001). We also observed enhancements in both motor conduction velocity and sensory conduction velocity of patients in bilateral median nerves, posterior tibial nerves, common ulnar nerves and peroneal nerves following repetitive transcranial magnetic stimulation treatment. Analysis of the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN 20-item scale data (17.68 ± 8.14 vs 10.50 ± 9.55, p &lt; 0.001) revealed significant reductions in scores. Patients with grade 2–3 ( n = 25) exhibited a mean reduction of 8.89 ± 4.24 points, while those with grade 4 ( n = 5) showed a difference value of 3.54 ± 3.45, p &lt; 0.001. No adverse events were observed. Conclusion: Our findings suggest that repetitive transcranial magnetic stimulation is a safe and effective therapeutic approach for ameliorating peripheral nerve injury and alleviating the chemotherapy-induced peripheral neuropathy symptoms in multiple myeloma patients. Early initiation of repetitive transcranial magnetic stimulation treatment may yield more favorable outcomes for these patients.

Differential symptom cluster responses to repetitive transcranial magnetic stimulation treatment in depression.

Repetitive transcranial magnetic stimulation (rTMS) can target specific neural circuits, which may allow for personalized treatment of depression. Treatment outcome is typically determined using sum scores from validated measurement scales; however, this may obscure differential improvements within distinct symptom domains. The objectives for this work were to determine: (1) whether a standard depression measure can be represented using a four symptom cluster model and (2) whether these symptom clusters had a differential response to rTMS treatment. Data were obtained from two multi-centre randomized controlled trials of rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC) for participants with treatment-resistant depression (TRD) conducted in Canada (THREE-D [Conducted between Sept 2013, and Oct 2016] and CARTBIND [Conducted between Apr 2016 and Feb 2018]). The first objective used confirmatory factor analytic techniques, and the second objective used a linear mixed effects model. Trial Registration: NCT01887782, NCT02729792. In the total sample of 596 participants with TRD, we found a model consisting of four symptom clusters adequately fit the data. The primary analysis using the THREE-D treatment trial found that symptom clusters demonstrated a differential response to rTMS treatment (F(3,5984)=31.92, p<0.001). The anxiety symptom cluster was significantly less responsive to treatment than other symptom clusters (t(6001)=-8.02, p<0.001). These findings were replicated using data from the CARTBIND trial. There are distinct symptom clusters experienced by individuals with TRD that have a differential response to rTMS. Future work will determine whether differing rTMS treatment targets have distinct patterns of symptom cluster responses with the eventual goal of personalizing rTMS protocols based on an individual's clinical presentation. Canadian Institutes of Health Research, Brain Canada.

Non-Conscious Negativity Bias as a Predictor of Depression Severity in TMS Patients

Abstract Background: Patients who undergo TMS (transcranial magnetic stimulation) are typically assessed using subjective rating scales. However, more objective assessments may lead to the development of biomarkers that may be better able to predict outcomes after TMS. In this study, we evaluated the non-conscious negativity bias test as an objective measure of depression severity. Design: This was a retrospective study of a convenience sample of 8 patients undergoing TMS treatment for major depression. Patients took a test of non-conscious negativity bias from a computerized platform (Total Brain). This test involved patients recognizing a facial emotional expression (fear, anger, disgust, sadness, happiness, or neutrality) as quickly as possible. After this first task, a set of two faces was presented, with one face repeated from the previous first task, and one face new. Both faces displayed the same emotion, and the task was to select the face seen from the previous task. Raw scores were time to correct responses for each of the four negative emotions (fear, sadness, anger, and disgust). Raw scores were converted to a percentile score based on age, education level, and gender. Percentiles of 1-30 were categorized as low, 30-70 as medium, and 70-100 as high. Results: Out of 4 patients who scored in the low category on the test, all of them (100%) rated their depression on the PHQ9 in the moderately severe to severe range (15-27). Out of the 4 who were not in the low category on the test, 1 rated their depression on the PHQ9 as severe (25%). Using the Fisher Exact test, the association between the variables approached significance (p=0.14). Discussion: In this retrospective study, results from an implicit negative bias test were suggestive of depression severity in patients undergoing TMS. A larger sample size may help clarify its use in real-world populations. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: TMS, Depression, Biomarker, Cognitive

Extension of transcranial magnetic stimulation treatment for depression in non-responders: Results of a naturalistic study

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) shows efficacy in the treatment of major depressive disorder using a standard course of 20–36 treatment sessions. However, research efforts are being made to improve overall response and remission rates. Evidence from open-label extension studies of randomized control trials suggests that extending the rTMS treatment course beyond 36 treatments may improve outcomes, however, little has been published on the benefit of extended TMS treatment courses in clinical practice. ObjectiveIn this retrospective naturalistic observational study, we studied response rates on continuation of rTMS following failure of the first round of 36 treatments. MethodsFrom 142 patients who received conventional rTMS and 29 who underwent theta-burst stimulation (TBS) at Massachusetts General Hospital TMS clinical service, 28 non-responders (23 to rTMS and 5 to TBS) opted to continue their treatment beyond session 36. The treatment protocol allowed personalization in target, TMS protocol, as well as number of pulses and sessions as clinically indicated. Sustained response and remission using Hamilton Rating Scale for Depression, 17-items (HAMD-17) was the primary outcome. ResultsThe average number of overall treatment sessions was 70.54 ± 16.73 for the sample. Overall, there was a 53.57% response rate and a 32.14% remission rate. Response and remission rates rose as the number of sessions increased and there did not appear to be a plateau in response over time. ConclusionOur results support the idea that subpopulation of TMS patients are late responders. Continuation of TMS up to 72 treatments among those patients who do not meet response criteria by session 36 may improve overall response rates. While the number of subjects and study design limit generalization, given the fact that these patients were medication refractory and had failed initial course of TMS, the result of this study is encouraging.

Management of Children with Speech Disorders via Transcranial Magnetic Stimulation: Non-Randomized Controlled Study

Background. Speech development impairment is urgent and common problem in pediatric neurology. Transcranial magnetic stimulation (TMS) is one of the promising treatment variants for children with speech disorders. Objective. The aim of the study is to evaluate efficacy and safety of the developed approaches to TMS usage in the management of children with speech disorders. Methods. It was non-randomized controlled study. It included 46 children with speech disorders aged from 3 to 6.5 years. All children were divided into two groups comparable by gender and age: 26 children of the treatment group received TMS course, 20 children of the control group received treatment with hopantenic acid. All patients with speech disorders underwent psychological and pedagogical evaluation of speech and cognitive development, electroencephalography (EEG) before and after treatment. Moreover, comparative analysis of TMS and nootropic therapy efficacy was carried out. Specialized examination of speech and cognitive development was also performed via E.A. Strebeleva method for psychological and pedagogical diagnosis of children development. Furthermore, we carried out side reactions / adverse events registration according to patients and/or their parents complaints confirmed by physical examination, patient’s behavior observation, data from specially developed questionnaire for assessing child’s behavior and well-being (filled up by parents). Finally, we evaluated brain bioelectric activity recorded by EEG. Results. The study results have shown that it is possible to achieve significant positive dynamics in cognitive and speech development in preschool children with speech disorders in both groups (TMS course and medical treatment). But hereby, TMS treatment has demonstrated significantly higher positive dynamics in two out of the three evaluated parameters. There were no cases of adverse events in TMS group leading to early course discontinuation. Conclusion. TMS is non-invasive and safe method for treatment of children with speech disorders. This study has demonstrated the efficacy of the method in the field of personalized management of children with impaired speech and cognitive development.

Changes of brain network characteristics in patients with depression before and after precise repetitive transcranial magnetic stimulation

Objective: To investigate the changes of brain network characteristics in patients with depression before and after precise repetitive transcranial magnetic stimulation (rTMS) treatment. Methods: Patients with depression in the Second Affiliated Hospital of Xinxiang Medical University and healthy volunteers in the community of Xinxiang city from February 2018 to March 2019 were simultaneously recruited. The left dorsolateral prefrontal cortex was precisely selected as the stimulation target through the latest Human Brainnetome Atlas, and the near infrared navigation was used to achieve accurate brain stimulation treatment in combination with the structural magnetic resonance data. Moreover, functional connectivity was analyzed before and after rTMS treatment in significantly altered brain areas of patients with depression. Results: Nineteen patients (11 males and 8 females) with depression were included, aged (34±11) years. Meanwhile, 22 healthy controls (9 males and 13 females), aged (30±9) years, were also enrolled. Functional connectivity of insular cortex was decreased in depression patients when the insula was analyzed as the target area (P<0.05). The functional connection from insula to middle frontal lobe and superior parietal lobe in patients with depression decreased before rTMS treatment (P<0.05), but increased after rTMS treatment (P<0.05). The functional connection between dIg_L of the insula and the right middle prefrontal lobe was correlated with Beck Anxiety Index (BAI) before rTMS treatment and Beck Depression Index (BDI) after rTMS treatment (r=0.737, P=0.003; r=0.696, P=0.005). Conclusions: Abnormal functional connectivity of insula may be the brain imaging mechanism of rTMS treatment. Precise brain region selection based on Human Brainnetome Atlas provides a new technical method for clinical rTMS precision treatment.

A Case Series of Deep Transcranial Magnetic Stimulation Treatment for Patients with Obsessive-Compulsive Disorder in the Tokyo Metropolitan Area.

Obsessive-compulsive disorder (OCD) is a chronic illness in which patients do not achieve remission sufficiently with conventional medication. Deep repetitive transcranial magnetic stimulation (dTMS) for OCD neuromodulates the bilateral anterior cingulate cortex (ACC) and dorsal medial prefrontal cortex (mPFC), which are known to be impaired in OCD. While dTMS treatment for OCD has shown effective results overseas, TMS treatment for OCD has rarely been implemented in Japan, and its effectiveness is unknown. We conducted an FDA-approved dTMS protocol to 26 patients with OCD. In addition, individual exposure stimulation that elicited each patient’s obsessive thoughts was also combined during dTMS treatment. Before and after 30 sessions of TMS treatment, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess changes in the severity of each patient’s obsessive-compulsive disorder. Response to dTMS treatment in patients with OCD was determined by whether the total score on the Y-BOCS after a course of treatment was reduced by 30% or more compared with the score at baseline. The percentage of responders in this case series following the 30 sessions of dTMS treatment was 53.9%. In addition, total Y-BOCS scores and scores on each item were significantly improved. The percent changes in total Y-BOCS scores did not differ between the sexes or between on- and off-medication patients. No obvious adverse events were observed in this case series. In line with the results of TMS studies for OCD patients reported overseas, dTMS treatment for Japanese patients with OCD may have a favorable therapeutic effect.

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder

The antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to be N-methyl-D-aspartate (NMDA)-receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD. To test whether low doses of the NMDA-receptor partial-agonist, D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD. This was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work (including complete blood cell count, electrolytes, liver function tests, and creatinine level). Participants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plus D-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4. The primary outcome was change in depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores. A total of 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]) were randomly assigned to treatment groups: iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plus D-cycloserine (mean [SD] baseline score, 30.4 [4.5]). The iTBS plus D-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group (mean difference, -6.15; 95% CI, -2.43 to -9.88; Hedges g = 0.99; 95% CI, 0.34-1.62). Rates of clinical response were higher in the iTBS plus D-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%). This was reflected in lower CGI-severity ratings and greater CGI-improvement ratings. No serious adverse events occurred. Findings from this clinical trial indicate that adjunctive D-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment outcomes in MDD using iTBS requiring further investigation. ClinicalTrials.gov Identifier: NCT03937596.

Effect of priming on adjunctive repetitive transcranial magnetic stimulation in treatment of late life depression: Protocol of a prospective randomized sham-controlled study.

AbstractObjectivePriming stimulation, which involves high-frequency repetitive transcranial magnetic stimulation (rTMS) followed by low-frequency, has been shown to enhance neural response and is one of the novel paradigms found beneficial in adult patients with depression and has not been studied in late-life depression (LLD). This study aims to compare the effect of adjunctive priming vis-a-vis no priming rTMS over right dorso-lateral prefrontal cortex (DLPFC), on treatment of LLD.MethodsThis trial is registered in Clinical Trial Registry-India (CTRI) on www.ctri.nic.in. CTRI registration number: CTRI/2020/08/027230. Forty patients of LLD who are symptomatic after an adequate antidepressant trial will be randomized into 2 groups (active priming and sham priming rTMS); each receiving 10 sessions of rTMS over 2 weeks. Patients will remain blind to treatment allocation. Assessments will be done using Hamilton rating scale for depression, Geriatric Depression Scale, Hamilton rating scale for Anxiety, Somatic Symptom Severity Scale 8, Hindi Mental Status Examination, and Clinical Global Impression scale at baseline, week 1, 2, and 4. Side effect checklist will be applied after each session in both groups and at the end of 4 weeks.ResultData will be analyzed using statistical software Statistical Package for Social Sciences. Both the groups (active and sham groups) will be compared at the four given timepoints. Also, the baseline characteristics will be compared with the 3 follow-up points for any change.ConclusionThe findings of the study will give an insight to the possible role of priming to augment the effect of low-frequency rTMS in LLD.

Effect of transcranial magnetic stimulation in combination with citalopram on patients with post-stroke depression.

BackgroundAmelioration of depression in patients with post-stroke depression (PSD) remains challenging.ObjectiveThe primary vision was to explore the effect of transcranial magnetic stimulation (TMS) in combination with citalopram on patients with PSD.MethodsOne hundred eligible patients who were diagnosed with PSD were recruited and randomly assigned to the control group (n = 50) or the TMS group (n = 50). The controls were given citalopram (10 mg/d for consecutive 8 weeks), while, in addition to citalopram, patients in the TMS group were also given TMS at 5 Hz once a workday for 8 weeks. The primary outcome was patient depression status as reflected by 17-item Hamilton Rating Scale for Depression (HAMD-17) score, and the secondary outcome was patient neuropsychological score determined by Mini-Mental State Examination (MMSE) and Wisconsin Card Sorting Test (WCST).ResultsPatients treated with TMS in combination with citalopram had a drastic decrease in HAMD-17 score during treatment. Bigger changes in HAMD-17 score between baseline and 2 weeks as well as between baseline and 8 weeks in the TMS group were observed (P < 0.01). Patients in both groups had increased MMSE scores after treatment. Data of WCST revealed patients with TMS treatment completed more categories (P < 0.01) and had a lower RPP in comparison to patients in the control group (P < 0.0001). Additionally, TMS in combination with citalopram strikingly improved patients' MMSE scores when compared with those taking citalopram alone. Last, there was no striking difference in side effects between the two groups (P > 0.05).ConclusionOur study found TMS in combination with citalopram is conducive to improving depression status and neuropsychological function, which holds great promise for treating PSD.

Transcranial Magnetic Stimulation for the treatment of late-life depression: A scoping review

Objective: Clinical utility of transcranial magnetic stimulation (TMS) in older adults with depression is less studied. This review was conducted with the aim to compile the study findings on efficacy and adverse effects of TMS in late-life depression, to elucidate gaps in the literature and to formulate recommendations. Method: A search was conducted on PubMed, SCOPUS and OVID data bases with search terms based on the three domains of our research questions namely “transcranial magnetic stimulation” (TMS), “depression” and “late life”. All the articles published in English till June 2021 were incorporated and critically appraised after fulfilling inclusion and exclusion criteria. Results: A total of 643 articles were screened with title and abstract and 41 were selected for full text assessment. Finally, 26 articles were included after scrutiny and findings were tabulated. This consisted of 8 Randomized Controlled Trials (RCTs), 6 Open label, 1 retrospective study, 4 case series and 7 case reports. Available findings in this area thus far, are mixed and inconclusive. Level I evidence for the use of TMS in late-life depression is lacking. Conclusion: Evidence regarding efficacy of TMS in treatment of depression in older adults lacks consistency in the outcomes, which warrants urgent need for systematic review and metanalysis of RCTs on use of TMS in late life depression.

2.54 A Naturalistic Study of Sequential Bilateral 1 Hz/20 Hz Transcranial Magnetic Stimulation Treatment for Adolescents With Treatment-Resistant Depression

Transcranial magnetic stimulation (TMS) is widely used for the treatment of depression in adults. There are knowledge and evidence gaps with respect to the application of TMS for adolescents with treatment-resistant depression. Recent studies have increasingly examined sequential bilateral treatments as a dosing strategy for both adults and adolescents with depression, suicidal ideation, and co-occurring conditions. This study sought to retrospectively examine off-label, naturalistic, sequential bilateral 1 Hz (right-sided) and 20 Hz (left-sided) TMS treatments in adolescents.

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Comorbid Nicotine Addiction with Major Depressive Disorder and Obsessive-Compulsive Disorder

Objective: Nicotine addiction is a common health problem in psychiatric disorders. The aim of this study was to analyze the effects of rTMS on comorbid nicotine addiction in patients receiving recurrent Transcranial Magnetic Stimulation (rTMS) therapy for major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). Method: Data of 32 patients (23 MDD, 9 OCD) were evaluated retrospectively. We compared the Hamilton Depression Rating Scale (HAM-D), Beck Anxiety Inventory (BAS), Yale-Brown Obsession Compulsion Scale (Y-BOCS), and Fagerström Test for Nicotine Dependence (FTND) scores at three time points (before treatment "0th week", at the end of treatment “6th week”, and 12 weeks after this assessment “18th week”). Results: The patients’ mean age was 40.47±10.20, 13(40.6%) were women. A significant reduction was found in HAM-D, BAS, FTND at weeks 6 (p&amp;lt;0.001 for all) and 18 (p&amp;lt;0.001 for all) compared to baseline scores. A binary logistic regression showed that changes in depression and anxiety symptoms were not associated with the changes in FTND ratings at weeks 6 and 18 (p=0.158, p=0.251, respectively). Conclusion: In this study, it can be said that rTMS treatment reduces the severity of nicotine addiction accompanying MDD and OCD, independent of the recovery of the psychiatric disease. This study suggests that rTMS can be an effective treatment for nicotine addiction comorbid with psychiatric disorders. We recommend placebo-controlled randomized double-blind studies.