Intermittent theta-burst stimulation (iTBS) is an established treatment for treatment-resistant depression (TRD). Sessions conducted more than once daily (ie, accelerated TBS [aTBS]) may enhance antidepressant effects. However, evidence is limited to small trials, and protocols are time-consuming and can require neuroimaging-based targeting.

To evaluate the efficacy and safety of a pragmatic aTBS protocol for TRD.

This triple-blinded, sham-controlled randomized clinical trial was conducted at a single center in São Paulo, Brazil, from July 2022 to June 2024, with a subsequent open-label phase. Patients aged 18 to 65 years with major depression, experiencing a TRD episode, and with a Hamilton Depression Rating Scale, 17-item (HDRS-17) score of 17 or higher were eligible for inclusion. Exclusion criteria were other psychiatric disorders (except anxiety), neurological conditions, and TBS contraindications.

Participants received 45 active or sham stimulation sessions over 15 weekdays, with 3 iTBS sessions (1200 pulses each) per day, spaced 30 minutes apart and targeting the left dorsolateral prefrontal cortex using a craniometric approach. In the open-label phase, additional aTBS sessions were offered to achieve a response (≥50% HDRS-17 score improvement) if needed.

The primary outcome was change in HDRS-17 score at week 5.

Of 431 volunteers screened, 100 participants were enrolled and randomized to either sham or active aTBS. Mean (SD) participant age was 41.7 (8.8) years, and 84 participants (84%) were female. A total of 89 patients completed the study. In the intention-to-treat analysis, the mean change in HDRS-17 scores from baseline to the study end point was 5.57 (95% CI, 3.99-7.16) in the sham group and 9.68 (95% CI, 8.11-11.25) in the active group, corresponding to 31.87% and 54.7% score reductions, respectively, and a medium-to-large effect size (Cohen d, 0.65; 95% CI, 0.29-1.00; P < .001). Response and remission rates were also higher in the active group. Both interventions were well tolerated, but scalp pain was more frequent in the active group than the sham group (17.4% vs 4.4%). During the open-label phase, approximately 75% of patients received additional sessions.

In this triple-blinded, sham-controlled randomized clinical trial, a pragmatic aTBS protocol using only 3 iTBS sessions per day and a nonexpensive, non-neuronavigated approach was found to be safe and effective for TRD.

ClinicalTrials.gov Identifier: NCT05388539.

Affective bias toward negativity is associated with depression and may represent a promising treatment target. Stimulating the dorsolateral prefrontal cortex (dlPFC) with deep Transcranial Magnetic Stimulation (dTMS) could lead to shifts in affective bias. The current study examined behavioral and neural correlates of affective bias in the context of dTMS in adolescents with treatment-resistant depression (TRD).

Adolescents completed a Word-Face Stroop (WFS) task during an fMRI scan before and after 30 sessions of dTMS targeting the left dlPFC. In the task, participants were shown words superimposed on faces in either a "congruent" (both word and face were positive or both negative) or an "incongruent" fashion; in both cases, participants identified whether the words were positive or negative. We examined pre-post intervention neural and behavioral WFS changes and their correlations with clinical improvement.

Usable pre- and post-intervention WFS data were available for 10 adolescents with TRD (Age, years: M = 16.3, SD = 1.09) for behavioral data; 9 for neuroimaging data. After treatment, although changes in behavioral performance did not suggest improved affective bias, amygdala activation decreased during the negative word/happy face condition, which correlated with clinical improvement. Overall, clinical improvement correlated with decreased neural activation during congruent conditions.

Major limitations include the small sample size, lack of a sham control group, and unknown psychometric properties.

Preliminary findings suggesting improving neural efficiency and normalizing affective bias in those with the most clinical improvement highlight the potential importance of targeting affective bias in treating adolescents with TRD.

Non-invasive brain stimulation targeting the left ventromedial prefrontal cortex (vmPFC) has shown potential in enhancing fear extinction. However, optimal stimulation parameters for clinical application remain unclear.

This study investigated the effects of intermittent theta burst stimulation (iTBS) on fear extinction using a three-day paradigm. Fifty healthy participants underwent fear acquisition (day 1), extinction learning (day 2), and both a spontaneous recovery and reinstatement test (day 3). Active or sham iTBS was applied before extinction learning to the left posterior PFC (MNI: -56, 2, 40), previously shown to be functionally connected to the vmPFC. Fear responses were measured using skin conductance responses (SCR) during CS+ and CS- presentations, along with arousal, valence, and contingency awareness ratings.

A significant time x group interaction was found for iTBS administered before extinction learning, with the active group showing reduced SCR during extinction learning compared to sham. However, no TMS effects were observed during the spontaneous recovery or reinstatement tests.

These findings suggest limited therapeutic potential for iTBS targeting the left posterior PFC in enhancing extinction memory consolidation. Further research is needed to determine optimal stimulation parameters for clinical application.

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.

Behavioral and neurobiological abnormalities in addiction and obesity have led to the theory of food addiction in obesity (FAOB) and brain-behavior association studies. Transcranial magnetic stimulation (TMS) studies and treats various brain disorders. Cortico-cortical paired associative stimulation TMS protocol, in which left lateral prefrontal cortex (LPFC) stimulation follows right LPFC stimulation, can reduce emotional reactivity to visual triggers and modulate prefrontal asymmetry in healthy adults. Accordingly, we examined the effects of acute ccPAS on food cravings and brain responses in FAOB.

Twenty-two adults (12 Active, 10 Sham) with FAOB participated in this single-blind, sham-controlled pilot study. Electroencephalogram was recorded during rest and a Food Stroop task, which were conducted before and after a single active or sham ccPAS session, consisting of 600 paired stimulation pulses of the right, then left LPFC, with inter-pulse interval of 8ms and a 3sec inter-pair-interval. Stroop bias changes following exposure to food images, alterations in the associated (emotionally laden) late positive event-related component (LPPb) total brain activity power, and frontal alpha band asymmetry during rest and task performance were investigated.

No baseline differences were detected between the groups, except for education level. Active (but not Sham) ccPAS elevated the Stroop bias and the total brain activity power over the left LPFC while no stimulation-related influence was found on the LPPb or prefrontal brain asymmetry during task and the resting state. However, the stimulation-induced change in the Stroop bias was negatively correlated with the change in LPPb magnitude, positively correlated with changes in asymmetrical activity during the task, and negatively with left frontal alpha asymmetry during rest.

The ccPAS affected food-related emotional regulation, probably due to general reduction of inhibitory control during task performance. Further studies are needed to affirm the results with larger samples and to elucidate the development of beneficial ccPAS protocol for obesity with food addiction.

Epilepsy presents a significant global health challenge, impacting millions worldwide. Alarmingly, over half of individuals living with epilepsy (PWE) also face concurrent medical conditions, with psychiatric complications, particularly depression, standing out as prevalent issues. The relationship between epilepsy and depression is complex and bidirectional, with approximately a quarter of adults with epilepsy receiving a diagnosis of depression. This complexity underscores the challenges in diagnosing depression in epilepsy patients, hindered by overlapping symptoms and distinct manifestations of depression in this population. Our review highlights that the use of most antidepressant pharmacotherapies does not increase the risk of seizure occurrences. On the contrary, compelling evidence suggests that such treatments may even decrease seizure frequency, offering hope for patients. In addition to pharmacology, non-pharmacological interventions are emerging as vital alternatives, enriching the therapeutic landscape. However, despite these promising avenues, a significant gap in our understanding persists, characterized by a lack of comprehensive, prospective research. Our review rigorously explores the latest pathophysiological insights linking depression and epilepsy while critically evaluating contemporary treatment paradigms for individuals grappling with these comorbid conditions. By focusing on the most current developments, this review aims to equip clinicians with cutting-edge knowledge, fostering a more nuanced and effective approach to managing the intricate interplay between epilepsy and comorbid depression.

F-8-coil repetitive transcranial magnetic stimulation (rTMS) and H-1-coil deep repetitive transcranial magnetic stimulation (dTMS) have been indicated for the treatment of major depressive disorder (MDD) in adult patients by applying different treatment protocols. Nevertheless, the evidence for long-term electrophysiological alterations in the cortex following prolonged TMS interventions, as assessed by quantitative electroencephalography (qEEG), remains insufficiently explored. This study aims to demonstrate the qEEG-based distinctions between rTMS and dTMS in the management of depression and to evaluate the potential correlation between the electrophysiological changes induced by these two distinct TMS interventions and the clinical improvement in depressive and anxiety symptoms.

A total of 60 patients diagnosed with treatment resistant depression received rTMS (n = 30) or dTMS (n = 30) along with their usual treatments in Kemal Arıkan Psychiatry Clinic. All the participants underwent resting-state qEEG recording before and at the end of 30 sessions of TMS treatment. The significant qEEG changes were then tested for their correlation with the improvement in depression and anxiety.

After the course of rTMS and dTMS a considerable reduction is seen in the severity of depression and anxiety. Although improvements in depression and anxiety were observed in both TMS groups, specific neural activity patterns were associated with better outcomes in depression. Patients who exhibited lower alpha activity in the left fronto-central region and higher gamma activity in the right prefrontal region following rTMS showed more significant improvements in depression symptoms. Similarly, those whose beta activity increased in the left prefrontal region but decreased in the right prefrontal region after rTMS tended to have greater reductions in depression and anxiety severity. For patients in the dTMS group, those who demonstrated a decrease in left temporal theta activity after treatment were more likely to experience a substantial improvement in depression severity.

Following 30 sessions of rTMS with a F8 coil and dTMS with an H1 coil, notable alterations in qEEG activity with clinical significance were discerned. The persistence of these changes should be investigated in the subsequent follow-up period.

The objective of this study was to reveal the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for Japanese patients with treatment-resistant depression (TRD) in clinical practice, based on real-world data from a nationwide multicenter observational study in Japan. Clinical data of patients with TRD treated with rTMS (NeuroStar TMS treatment system) under public insurance coverage were retrospectively collected from 21 institutes nationwide between June 2019 and December 2023. Depression severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). Response and remission were defined as ≥50 % reduction from baseline and ≤7 points on the HAMD-17, respectively. The primary outcome was the changes in the HAMD-17 score from baseline to the endpoint following rTMS. Data from 497 patients with TRD were candidates for this study. The HAMD-17 scores (mean (SD)) improved significantly from 18.9 (5.3) to 9.7 (6.6), respectively. The response and remission rates at the end of rTMS therapy as assessed by the HAMD-17 were 53.5 % and 42.8 %, respectively. The dropout rate due to adverse effects was 4.2 %, and the treatment was generally well tolerated. No convulsive seizures or manic changes were observed. These results indicate that conventional rTMS is effective and safe in Japanese patients with TRD.

Background: Glioblastoma multiforme is an aggressive malignancy with a dismal 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier (BBB). We have previously shown that high-amplitude repetitive transcranial magnetic stimulation (rTMS) in rats allowed the delivery across the BBB of an IGF signaling inhibitor-IGF-Trap. The objective of this study was to assess the therapeutic effect of IGF-Trap when delivered in conjunction with rTMS on the intracerebral growth of glioma. Results: We found that systemic administration of IGF-Trap without rTMS had a minimal effect on the growth of orthotopically injected glioma cells in rats and mice, compared to control animals injected with vehicle only or treated with sham rTMS. In rats treated with a combination of rTMS and IGF-Trap, we observed a growth retardation of C6 tumors for up to 14 days post-tumor cell injection, although tumors eventually progressed. In mice, tumors were detectable in all control groups by 14-17 days post-injection of glioma GL261 cells and progressed rapidly thereafter. In mice treated with rTMS prior to IGF-Trap administration, tumor growth was inhibited or delayed, although the tumors also eventually progressed. Conclusion: The results showed that rTMS could increase the anti-tumor effect of IGF-Trap during the early phases of tumor growth. Further optimization of the rTMS protocol is required to improve survival outcomes.

Perceived purpose in life (PIL) is linked with many vital health outcomes, including Major Depressive Disorder (MDD).

In this study, biomarkers associated with depression and PIL were investigated using Brain Network Activation (BNA) based quantitative electroencephalography (QEEG) and event-related potential (ERP) measures in a sample of individuals with MDD. Data were analyzed before and after a 36-session, Deep transcranial magnetic stimulation (TMS) program.

At baseline, the study observed that increased slow-frequency resting-state activity in the frontal and temporal regions correlated with higher levels of depression and reduced PIL. Additionally, a reduced P3b amplitude was found to predict elevated depressive symptoms. However, with the application of Deep TMS treatment notable improvements were observed in both depression (p < .001. d = 2.15) and PIL (p < .001, d = 1.59) levels. The treatment also successfully regulated resting-state QEEG (delta/beta) and ERP characteristics (P200 latency), bringing them closer to healthy levels.

This attenuation of brain activity patterns relating to depression is encouraging as it suggests that effects were robust and are more likely to be sustained over time. This study represents the first exploration of the effects of Deep TMS on PIL and relevant QEEG and ERP biomarkers. The initial evidence suggests that Deep TMS holds promise in enhancing both PIL and neurophysiological health. Future investigations should continue exploring the utility of Deep TMS in targeting a wide range of neuropsychological and physical health conditions, leveraging objective biomarkers such as QEEG and ERP.

Objective.Recent studies have indicated that repetitive transcranial magnetic stimulation (rTMS) could enhance cognition in Alzheimer's Disease (AD) patients, but to now the molecular-level interaction mechanisms driving this effect remain poorly understood. While cognitive scores have been the primary measure of rTMS effectiveness, employing molecular-based approaches could offer more precise treatment predictions and prognoses. To reach this goal, it is fundamental to assess the electric field (E-field) and the induced current densities (J) within the stimulated brain areas and to translate these values toin vitrosystems specifically devoted in investigating molecular-based interactions of this stimulation.Approach.This paper offers a methodological procedure to guide dosimetric assessment to translate the E-field induced in humans (in a specific pilot study) intoin vitrosettings. Electromagnetic simulations on patients' head models and cellular holders were conducted to characterize exposure conditions and determine necessary adjustments forin vitroreplication of the same dose delivered in humans using the same stimulating coil.Main results.Our study highlighted the levels of E-field andJinduced in the target brain region and showed that the computed E-field andJwere different among patients that underwent the treatment, so to replicate the exposure to thein vitrosystem, we have to consider a range of electric quantities as reference. To match the E-field to the levels calculated in patients' brains, an increase of at least the 25% in the coil feeding current is necessary whenin vitrostimulations are performed. Conversely, to equalize current densities, modifications in the cells culture medium conductivity have to be implemented reducing it to one fifth of its value.Significance.This dosimetric assessment and subsequent experimental adjustments are essential to achieve controlledin vitroexperiments to better understand rTMS effects on AD cognition. Dosimetry is a fundamental step for comparing the cognitive effects with those obtained by stimulating a cellular model at an equal dose rigorously evaluated.

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy.

The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively.

We studied healthy older adult participants (N = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task.

Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation.

The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for acute treatment of major depressive disorder (MDD). However, the efficacy and optimal strategy of delivering maintenance rTMS beyond acute treatment remains unclear. This meta-analysis aims to quantify the treatment effect of maintenance rTMS therapy in MDD and compares the difference in treatment effect between the fixed and rescue maintenance rTMS protocols. We conducted a meta-analysis of 14 studies (N = 705) comparing depression rating scores before and after maintenance rTMS. Standardized mean scores adjusted for sample size (Hedges g) were used as the effect size. Subgroup analysis was performed to compare the fixed and rescue maintenance rTMS treatment. Maintenance rTMS was associated with a statistically significant improvement in depression scores (standardized mean difference [SMD] = 0.75; confidence interval [CI] = -1.25 to -0.25). The random effects model had the Q value = 142.67 (P < 0.0001) and I2 = 90%, supporting significant heterogeneity among studies. The prediction interval yielded a possible effect size from -2.54 to 1.05. The subgroup analysis showed a stronger treatment effect for rescue maintenance protocol (SMD = -1.17; CI = -2.13 to -0.21) compared to fixed maintenance protocol (SMD = -0.45; CI = -1.00.16). Although not statistically significant (Q-between = 2.56, df-between = 1, P = 0.1096), a large difference in effect size was observed between subgroups. Maintenance rTMS appears to be an effective strategy for maintaining remission and preventing relapse in MDD. Significant heterogeneity among the studies warrants caution in interpreting the results. These findings suggest the need for standard protocols and consensus guidelines for the optimal delivery of maintenance rTMS treatment.

Depression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field.

We retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps.

A total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as "Default Mode Network," "Functional Connectivity," and "Theta Burst" have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels.

In recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots.

The estimated lifetime prevalence of post-traumatic stress disorder (PTSD) in adults worldwide has been estimated at 3.9%. PTSD appears to contribute to alterations in neuronal network connectivity patterns. Current pharmacological and psychotherapeutic treatments for PTSD are associated with inadequate symptom improvement and high dropout rates. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive therapy involving induction of electrical currents in cortical brain tissue, may be an important treatment option for PTSD to improve remission rates and for people who cannot tolerate existing treatments.

To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on post-traumatic stress disorder (PTSD) in adults.

We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two clinical trials registers. We checked reference lists of relevant articles. The most recent search was January 2023.

We included randomized controlled trials (RCTs) assessing the efficacy and safety of rTMS versus sham rTMS for PTSD in adults from any treatment setting, including veterans. Eligible trials employed at least five rTMS treatment sessions with both active and sham conditions. We included trials with combination interventions, where a pharmacological agent or psychotherapy was combined with rTMS for both intervention and control groups. We included studies meeting the above criteria regardless of whether they reported any of our outcomes of interest.

Two review authors independently extracted data and assessed the risk of bias in accordance with Cochrane standards. Primary outcomes were PTSD severity immediately after treatment and serious adverse events during active treatment. Secondary outcomes were PTSD remission, PTSD response, PTSD severity at two follow-up time points after treatment, dropouts, and depression and anxiety severity immediately after treatment.

We included 13 RCTs in the review (12 published; 1 unpublished dissertation), with 577 participants. Eight studies included stand-alone rTMS treatment, four combined rTMS with an evidence-based psychotherapeutic treatment, and one investigated rTMS as an adjunctive to treatment-as-usual. Five studies were conducted in the USA, and some predominantly included white, male veterans. Active rTMS probably makes little to no difference to PTSD severity immediately following treatment (standardized mean difference (SMD) -0.14, 95% confidence interval (CI) -0.54 to 0.27; 3 studies, 99 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision (sample size insufficient to detect a difference of medium effect size). We deemed one study as having a low risk of bias and the remaining two as having 'some concerns' for risk of bias. A sensitivity analysis of change-from-baseline scores enabled inclusion of a greater number of studies (6 studies, 252 participants). This analysis yielded a similar outcome to our main analysis but also indicated significant heterogeneity in efficacy across studies, including two studies with a high risk of bias. Reported rates of serious adverse events were low, with seven reported (active rTMS: 6; sham rTMS: 1). The evidence is very uncertain about the effect of active rTMS on serious adverse events (odds ratio (OR) 5.26, 95% CI 0.26 to 107.81; 5 studies, 251 participants; very low-certainty evidence [Active rTMS: 23/1000, sham rTMS: 4/1000]). We downgraded the evidence by one level for risk of bias and two levels for imprecision. We rated four of five studies as having a high risk of bias, and the fifth as 'some concerns' for bias. We were unable to assess PTSD remission immediately after treatment as none of the included studies reported this outcome.

Based on moderate-certainty evidence, our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation. However, significant heterogeneity in efficacy was detected when we included a larger number of studies in sensitivity analysis. We observed considerable variety in participant and protocol characteristics across studies included in this review. For example, studies tended to be weighted towards inclusion of either male veterans or female civilians. Studies varied greatly in terms of the proportion of the sample with comorbid depression. Study protocols differed in treatment design and stimulation parameters (e.g. session number/duration, treatment course length, stimulation intensity/frequency, location of stimulation). These differences may affect efficacy, particularly when considering interactions with participant factors. Reported rates of serious adverse events were very low (< 1%) across active and sham conditions. It is uncertain whether rTMS increases the risk of serious adverse event occurrence, as our certainty of evidence was very low. Studies frequently lacked clear definitions for serious adverse events, as well as detail on tracking/assessment of data and information on the safety population. Increased reporting on these elements would likely aid the advancement of both research and clinical recommendations of rTMS for PTSD. Currently, there is insufficient evidence to meta-analyze PTSD remission, PTSD treatment response, and PTSD severity at different periods post-treatment. Further research into these outcomes could inform the clinical use of rTMS. Additionally, the relatively large contribution of data from trials that focused on white male veterans may limit the generalizability of our conclusions. This could be addressed by prioritizing recruitment of more diverse participant samples.

To provide guidance for the optimal administration of repetitive transcranial magnetic stimulation, based on scientific evidence and supplemented by expert clinical consensus.

Articles and information were sourced from existing guidelines and published literature. The findings were then formulated into consensus-based recommendations and guidance by the authors. The guidelines were subjected to rigorous successive consultation within the RANZCP, involving the Section of ECT and Neurostimulation (SEN) Committee, its broader membership and expert committees.

The RANZCP professional practice guidelines (PPG) for the administration of rTMS provide up-to-date advice regarding the use of rTMS in clinical practice. The guidelines are intended for use by psychiatrists and non-psychiatrists engaged in the administration of rTMS to facilitate best practice to optimise outcomes for patients. The guidelines strive to find the appropriate balance between promoting best evidence-based practice and acknowledging that evidence for rTMS use is a continually evolving.

The guidelines provide up-to-date advice for psychiatrists and non-psychiatrists to promote optimal standards of rTMS practice.

Treatment and management for difficult-to-treat depression are challenging, especially in a subset of patients who are at high risk for relapse and recurrence. The conditions that represent this subset are recurrent depressive disorder (RDD) and bipolar disorder (BD). In this context, we aimed to examine the effectiveness of maintenance transcranial magnetic stimulation (TMS) on a real-world clinical basis by retrospectively extracting data from the TMS registry data in Tokyo, Japan.

Data on patients diagnosed with treatment-resistant RDD and BD who received maintenance intermittent theta burst stimulation (iTBS) weekly after successful treatment with acute iTBS between March 2020 and October 2023 were extracted from the registry.

All patients (21 cases: 10 cases with RDD and 11 cases with BD) could sustain response, and 19 of them further maintained remission. In this study, maintenance iTBS did not exacerbate depressive symptoms in any of the cases, but may rather have the effect of stabilizing the mental condition and preventing recurrence.

This case series is of great clinical significance because it is the first study to report on the effectiveness of maintenance iTBS for RDD and BD, with a follow-up of more than 2 years. Further validation with a randomized controlled trial design with a larger sample size is warranted.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Currently available therapeutic modalities for alcohol use disorder (AUD) produce limited effect sizes or long-term compliance. Recent methods that were developed to modulate brain activity represent potential novel treatment options. Various methods of brain stimulation, when applied repeatedly, can induce long-term neurobiological, behavioral, and cognitive modifications. Recent studies in alcoholic subjects indicate the potential of brain stimulation methods to reduce alcohol craving, consumption, and relapse. Specifically, deep brain stimulation (DBS) of the nucleus accumbens or non-surgical stimulation of the dorsolateral prefrontal cortex (PFC) or medial PFC and anterior cingulate cortex using transcranial magnetic stimulation (TMS) has shown clinical benefit. However, further preclinical and clinical research is needed to establish understanding of mechanisms and the treatment protocols of brain stimulation for AUD. While efforts to design comparable apparatus in rodents continue, preclinical studies can be used to examine targets for DBS protocols, or to administer temporal patterns of pulsus similar to those used for TMS, to more superficial targets through implanted electrodes. The clinical field will benefit from studies with larger sample sizes, higher numbers of stimulation sessions, maintenance sessions, and long follow-up periods. The effect of symptoms provocation before and during stimulation should be further studied. Larger studies may have the power to explore predictive factors for the clinical outcome and thereby to optimize patient selection and eventually even develop personalization of the stimulation parameters.

Major Depressive Disorder (MDD) is a pervasive psychiatric condition effecting approximately 21 million adults in the U.S. (8.4%). An estimated 30-60% of patients are resistant to traditional treatment approaches (medications and talk-therapy), alluding to the need for additional options. Two promising treatment modalities include transcranial magnetic stimulation (TMS) and ketamine infusions; both have shown efficacy in standalone studies but have scarcely been investigated synergistically in the same group of participants.

In the current study, 169 participants with treatment-resistant MDD received 36 treatments of Deep TMS-only (H1 + H7 protocols), while 66 received 36 treatments of Deep TMS (H1 + H7 protocols) and 6 IV infusions of ketamine over the course of 9 weeks. Depressive symptoms were compared pre- and -post treatment in both conditions using the PHQ-9.

In both treatment groups, depressive symptoms were significantly reduced from pre-to-post and there were no significant differences in response between the TMS + ketamine condition and the TMS-only condition. The TMS + ketamine condition had an 80.30% response rate (53 out of 66) and 43.42% remission rate (28 out of 66) compared to a 76.92% response (130 out of 169) and 39.64% remission (67 out of 16) in the TMS-only condition.

These results support the notion that TMS treatments yield high response rates in treatment-resistant cases; however, in this investigation there was no added benefit for including 6 sessions of IV ketamine in conjunction with TMS. Future investigations using randomized-control designs and robust outcome measures are warranted.

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.

The efficacy and safety of deep transcranial magnetic stimulation (dTMS) in treating treatment-resistant depression (TRD) are unknown. Up to June 21, 2023, we conducted a systematic search for RCTs, and then extracted and synthesized data using random effects models. Five RCTs involving 507 patients with TRD (243 in the active dTMS group and 264 in the control group) were included in the present study. The active dTMS group showed significantly higher study-defined response rate (45.3% versus 24.2%, n = 507, risk ratio [RR] = 1.87, 95% confidence interval [CI]: 1.21-2.91, I2 = 53%; P = 0.005) and study-defined remission rate (38.3% versus 14.4%, n = 507, RR = 2.37, 95%CI: 1.30-4.32, I2 = 58%; P = 0.005) and superiority in improving depressive symptoms (n = 507, standardized mean difference = -0.65, 95%CI: -1.11--0.18, I2 = 82%; P = 0.006) than the control group. In terms of cognitive functions, no significant differences were observed between the two groups. The two groups also showed similar rates of other adverse events and all-cause discontinuations (P > 0.05). dTMS is an effective and safe treatment strategy for the management of patients with TRD.

Transcranial magnetic stimulation (TMS) is an intervention for treatment-resistant depression (TRD) that modulates neural activity. Deep TMS (dTMS) can target not only cortical but also deeper limbic structures implicated in depression. Although TMS has demonstrated safety in adolescents, dTMS has yet to be applied to adolescent TRD.

This pilot study evaluated the safety, tolerability, and clinical effects of dTMS in adolescents with TRD. We hypothesized dTMS would be safe, tolerable, and efficacious for adolescent TRD.

15 adolescents with TRD (Age, years: M = 16.4, SD = 1.42) completed a six-week daily dTMS protocol targeting the left dorsolateral prefrontal cortex (BrainsWay H1 coil, 30 sessions, 10 Hz, 3.6 s train duration, 20s inter-train interval, 55 trains; 1980 total pulses per session, 80 % to 120 % of motor threshold). Participants completed clinical, safety, and neurocognitive assessments before and after treatment. The primary outcome was depression symptom severity measured by the Children's Depression Rating Scale-Revised (CDRS-R).

14 out of 15 participants completed the dTMS treatments. One participant experienced a convulsive syncope; the other participants only experienced mild side effects (e.g., headaches). There were no serious adverse events and minimal to no change in cognitive performance. Depression symptom severity significantly improved pre- to post-treatment and decreased to a clinically significant degree after 10 treatment sessions. Six participants met criteria for treatment response.

Main limitations include a small sample size and open-label design.

These findings provide preliminary evidence that dTMS may be tolerable and associated with clinical improvement in adolescent TRD.

Transcranial magnetic stimulation (TMS) is a popular method for the noninvasive stimulation of neurons in the brain. It has become a standard instrument in experimental brain research and has been approved for a range of diagnostic and therapeutic applications. These applications require appropriately shaped coils. Various applications have been established or approved for specific coil designs with their corresponding spatial electric field distributions. However, the specific coil implementation may no longer be appropriate from the perspective of available material and manufacturing opportunities or considering the latest understanding of how to achieve induced electric fields in the head most efficiently. Furthermore, in some cases, field measurements of coils with unknown winding or a user-defined field are available and require an actual implementation. Similar applications exist for magnetic resonance imaging coils.

This work aims at introducing a complete formalism free from heuristics, iterative optimization, and ad-hoc or manual steps to form practical stimulation coils with individual turns to either equivalently match an existing coil or produce a given field. The target coil can reside on practically any sufficiently large or closed surface adjacent to or around the head.

The method derives an equivalent field through vector projection exploiting the well-known Huygens' and Love's equivalence principle. In contrast to other coil design or optimization approaches recently presented, the procedure is an explicit forward Hilbert-space vector projection or basis change. For demonstration, we map a commercial figure-of-eight coil as one of the most widely used devices and a more intricate coil recently approved clinically for addiction treatment (H4) onto a bent surface close to the head for highest efficiency and lowest field energy.

The resulting projections are within ≤4% of the target field and reduce the necessary pulse energy by more than 40%.

Background Of late, the interest in accelerated treatment protocols in repetitive transcranial magnetic stimulation (TMS) for the treatment of depression and obsessive-compulsive disorder (OCD) has been gaining momentum. Studies have already found that the patterned theta burst stimulation is non-inferior to the standard high-frequency stimulation in treating depression. The objective of the present study was to evaluate the clinical efficacy of a customized accelerated combination TMS naturalistic setting. Methods Retrospective analysis of pre and post-deep repetitive TMS responses in depression and OCD patients was performed. About 391 Depression and 239 OCD patients' data was analyzed. Customized treatment protocols consisted of twice daily high-frequency stimulations intervened by one theta burst stimulation. The outcome measures were a day six score in depression and a day 10 score in OCD, compared to day one baseline scores. Results The overall response rate in depression was 60.86%, estimated as a >50% reduction in the Hamilton Depression Rating Scale (HAM-D) 21 items score, and 62.76% in OCD, estimated as a >35% reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score. The mean reduction of YBOCS and HAM-D was statistically significant at p<0.0001 (Mann-Whitney U test statistic=9442.5, z=12.66 for YBOCS and 16673.5, z=18.92 for HAM-D). Corresponding effect size estimations revealed Cohen's d value of 1.40 and 1.59, respectively. Conclusions The response rates achieved at day six and day 10 in depression and OCD, respectively, were comparable to previous studies employing standard treatment protocols. The accelerated protocol produced satisfactory short-term clinical outcomes that were effective in the early management of the illness without any serious adverse effects.

TMS is increasingly used to treat depression, but predictors of treatment outcomes remain unclear. We assessed the association between age and TMS response given inconsistent prior reports limited by small sample size, heterogeneity, outdated TMS parameters, lack of assessment of H1-coil TMS, and lack of an a priori hypothesis. We hypothesized that older age would be associated with better treatment response based on trends in recent large exploratory analyses.

We conducted a naturalistic retrospective analysis of patients (n = 378) ages 18-80 with depression (baseline Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) > 5) who received 29-35 sessions of TMS between 2014 and 2021. Response was assessed using percent reduction of QIDS-SR. The relationship between percent response or remission and age group was assessed using the chi-square test.

85 % of patients received the standard protocol of H1-coil TMS to the left DLPFC. Percent response and remission rates for the entire study sample increased with age (response: p = .026; remission: p = .0023). This finding was stronger in female patients (response: p = .0033; remission: p = .00098) and was not observed in male patients (response: p = .73; remission: p = .26). This was confirmed in a sub-analysis of patients who only received the standard protocol with the H1-coil for the entire treatment course.

Naturalistic retrospective analysis from one academic center.

Older age is associated with a better antidepressant response to H1-coil TMS in female patients. This was demonstrated in a hypothesis-driven confirmation of prior exploratory findings in a large sample size with a homogeneous data collection protocol across all participants.

Cognitive impairment is a prevalent consequence of stroke, seriously affecting recovery and quality of life while imposing substantial burdens on both patients' families and society. Repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for post-stroke cognitive impairment (PSCI). However, the a lack of standardized and explicit guidelines regarding rTMS application parameters. Therefore, this study systematically evaluated the efficacy of various parameters of rTMS in treating PSCI and explored its potential mechanism.

We conducted a comprehensive search across seven scientific databases, namely China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), China Science and Technology Journal Database (VIP), Web of Science, PubMed, Embase, and Cochrane Library, to identify randomized controlled trials (RCTs) investigating the efficacy of rTMS for PSCI. The search encompassed the period from database creation until July 28, 2023. To evaluate the risk of bias in included studies, we employed the Cochrane recommended risk of bias assessment tool. Furthermore, we extracted relevant clinical application parameters associated with rTMS and performed comparative analyses to assess their therapeutic effects under different parameter settings.

The present study included 45 RCTs involving a total of 3,066 patients with PSCI. Both high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) demonstrated safety and efficacy, yet failed to exhibit significant differentiation in terms of cognitive improvement. Furthermore, intermittent theta burst stimulation (iTBS), although yielding positive results, did not surpass traditional rTMS in effectiveness. Combining HF-rTMS with LF-rTMS resulted in superior efficacy compared to single rTMS intervention. Moreover, the combination of rTMS with other cognitive therapies exhibited potential for enhanced benefits among patients.

rTMS can effectively and safely enhance cognitive function, improve quality of life, and enhance activities of daily living in patients with PSCI. Furthermore, the combination of rTMS with other conventional rehabilitation methods can yield additional positive effects. However, due to insufficient evidence, an optimal parameter protocol for rTMS can not be currently recommended. Future research should prioritize orthogonal experimental design methods that incorporate multiple parameters and levels to determine the optimal parameter protocol for rTMS in PSCI.

In the same way that beauty lies in the eye of the beholder, what a stimulus does to the brain is determined not simply by the nature of the stimulus but by the nature of the brain that is receiving the stimulus at that instant in time. Over the past decades, therapeutic brain stimulation has typically applied open-loop fixed protocols and has largely ignored this principle. Only recent neurotechnological advancements have enabled us to predict the nature of the brain (i.e., the electrophysiological brain state in the next instance in time) with sufficient temporal precision in the range of milliseconds using feedforward algorithms applied to electroencephalography time-series data. This allows stimulation exclusively whenever the targeted brain area is in a prespecified excitability or connectivity state. Preclinical studies have shown that repetitive stimulation during a particular brain state (e.g., high-excitability state), but not during other states, results in lasting modification (e.g., long-term potentiation) of the stimulated circuits. Here, we survey the evidence that this is also possible at the systems level of the human cortex using electroencephalography-informed transcranial magnetic stimulation. We critically discuss opportunities and difficulties in developing brain state-dependent stimulation for more effective long-term modification of pathological brain networks (e.g., in major depressive disorder) than is achievable with conventional fixed protocols. The same real-time electroencephalography-informed transcranial magnetic stimulation technology will allow closing of the loop by recording the effects of stimulation. This information may enable stimulation protocol adaptation that maximizes treatment response. This way, brain states control brain stimulation, thereby introducing a paradigm shift from open-loop to closed-loop stimulation.

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well-established treatment for major depressive disorder (MDD). Deep TMS utilizes specially designed H-Coils to stimulate the deep and broad cerebral regions associated with the reward system. The improved depth penetration of Deep TMS may be particularly important in late-life patients who often experience brain atrophy. The aim of this phase IV open-label study was to evaluate the safety and efficacy of Deep TMS in patients with late-life MDD. Data were collected from 247 patients with MDD aged 60-91 at 16 sites who had received at least 20 Deep TMS sessions for MDD. The outcome measures included self-assessment questionnaires (Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory-II (BDI-II)) and clinician-based scales (21-item Hamilton Depression Rating Scale (HDRS-21)). Following 30 sessions of Deep TMS, there was a 79.4% response and 60.3% remission rate on the most rated scale. The outcomes on the PHQ-9 were similar (76.6% response and 54.7% remission rate). The highest remission and response rates were observed with the HDRS physician-rated scale after 30 sessions (89% response and a 78% remission rate). After 20 sessions, there was a 73% response and 73% remission rate on the HDRS. Consistent with prior studies, the median onset of response was 14 sessions (20 days). The median onset of remission was 15 sessions (23 days). The treatment was well tolerated, with no reported serious adverse events. These high response and remission rates in patients with treatment-resistant late-life depression suggest that Deep TMS is a safe, well-tolerated and effective treatment for this expanded age range of older adults.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by both motor and non-motor symptoms, many of which are resistant to currently available treatments. Since the discovery that non-invasive transcranial magnetic stimulation (TMS) can cause dopamine release in PD patients, there has been growing interest in the use of TMS to fill existing gaps in the treatment continuum for PD. This review evaluates the safety and efficacy of a unique multifocal, bilateral Deep TMS protocol, which has been evaluated as a tool to address motor and non-motor symptoms of PD. Six published clinical trials have delivered a two-stage TMS protocol with an H-Coil targeting both the prefrontal cortex (PFC) and motor cortex (M1) bilaterally (220 PD patients in total; 108 from two randomized, sham-controlled studies; 112 from open label or registry studies). In all studies TMS was delivered to M1 bilaterally (Stage 1) and then to the PFC bilaterally (Stage 2) with approximately 900 pulses per stage. For Stage 1 (M1), two studies delivered 10 Hz at 90% motor threshold (MT) while four studies delivered 1 Hz at 110% MT. For Stage 2 (PFC), all studies delivered 10 Hz at 100% MT. The results suggest that this two-stage Deep TMS protocol is a safe, moderately effective treatment for motor symptoms of PD, and that severely impaired patients have the highest benefits. Deep TMS also improves mood symptoms and cognitive function in these patients. Further research is needed to establish optimal dosing and the long-term durability of treatment effects.

This meta-analysis investigated the therapeutic efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for treatment of post-stroke depression (PSD).

Ten articles with 266 patients in rTMS group and 258 patients in control group were included. The primary outcome was performed to examine the efficacy of rTMS for PSD. Secondary outcomes of response rates and remission rates and subgroup analyses were further explored.

Our meta-analysis revealed a significant pooled effect size (the standard mean difference (SMD) was -1.45 points (95% CI, -2.04 to -0.86; p < 0.00001)). The odds ratio (OR) of the response rate and remission rate were 8.41 (95% CI, 2.52-28.12, p = 0.0005) and 6.04 (95% CI, 1.5-24.39, p = 0.01). Moreover, rTMS treatment for PSD patients in subacute phase and targeting the left DLPFC at 5-cm anterior to the left motor hotspot or the midpoint of the middle frontal gyrus showed significant antidepressant effect. In addition, the Hamilton Depression Rating Scale (HAMD) was sensitive to detect depressive changes in patients.

Our meta-analysis elucidated that the application of high-frequency rTMS over the left DLPFC was an effective treatment alternative for PSD.

Our meta-analysis may help to develop more reasonable treatment strategies in clinical practice for PSD patients.

Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD.

This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up.

There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: -0.72; Z=-2.33, p=0.02).

This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

The magnitude of the placebo response depends on both the modality used as the "placebo" and the intervention with which it is compared, both of which can complicate the interpretation of randomized controlled trials (RCTs) for depression in late life. Given that neurostimulation and pharmacotherapy are among the most common interventions studied for late-life depression, comparing the relative placebo responses in studies of these interventions can aid interpretation of relative effect sizes.

We analyzed data from two RCTs of adults aged ≥60 years in an episode of treatment-resistant major depression, one comparing aripiprazole and matching placebo pills and the other comparing deep repetitive transcranial magnetic stimulation (rTMS) and sham rTMS. In both RCTs, depression was assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary comparison occurred after four weeks using analysis of covariance (ANCOVA) of HDRS-17 scores in participants who received placebo pills or sham rTMS. Relevant covariates included years of education, duration of depressive episode, and baseline HDRS-17 score.

Accounting for covariates, there was a larger reduction of HDRS-17 after four weeks in the sham rTMS group (estimated marginal mean ± SE: -5.90 ± 1.45; 95% CI: [-8.82, 2.98]) than in the placebo pills group (-1.07 ± 1.45; [-3.98, 1.85]). There were no significant differences between these groups in the binary outcome analysis of response and remission rates at four weeks or any outcome at trial end point comparison.

Sham rTMS may have a larger placebo response than placebo pills early in the treatment of older adults with treatment-resistant depression. Differential placebo responses should be considered in both the interpretation and design of RCTs.

To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges' g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges' g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.