rTMS Protocol Research Articles

History and Future Directions of rTMS for Treatment of Depressive Disorders

History and Future Directions of rTMS for Treatment of Depressive Disorders

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

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study.

Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied. We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention. rTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study. This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects. www.ClinicalTrials.gov, identifier: NCT05187000.

Efficacy of Repetitive Transcranial Magnetic Stimulation on spasticity in Egyptian Multiple Sclerosis Patients

Background; One of the most common neurologic disorders is multiple sclerosis. To improve quality of life, many tools have been employed. Repetitive transcranial magnetic stimulation (rTMS) is a new established technique to treat spasticity and improve the outcome of rehabilitation program in various neurologic conditions. Aim and objectives; To assess the effect of high frequency rTMS on improving spasticity in a sample of Egyptian MS patients. Patients and methods; 40 patients were recruited from the MS unit at Al-Azhar University hospitals with established diagnosis of MS and spasticity. Recruitment started from beginning of Jan, 2022 for 6 months. Patients were then randomly allocated into two groups: Study Group: 20 patients received 12 sessions of high frequency (HF) rTMS over the period of 3 weeks, followed by physical therapy (PT) for 30 minutes. rTMS protocol: Contralateral primary motor cortex (M1) was the site of stimulation. 1500 pulses (50 pulses per train with total 30 trains) per session with an intensity of 90% of the resting motor threshold at a frequency of 10 Hz were received. Each train had duration of 30 sec with inter- train delay of 25 seconds. Control Group: 20 patients received only physical therapy (PT) of 30 minutes over the period of 3 weeks). Results: The both groups received their medical treatment and physiotherapy. Compared with the control group, the study group had a statistically significant improvement. Conclusion: High frequency r-TMS could be beneficial in reducing spasticity and enhancing motor recovery in Egyptian MS patients.

Clinical Practice Guidelines for the Therapeutic Use of Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders.

Clinical Practice Guidelines for the Therapeutic Use of Repetitive Transcranial Magnetic Stimulation in Neuropsychiatric Disorders.

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.

Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the aftereffects observed. Here, we examined whether single sessions of a 15 Hz rTMS protocol, administered at suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Six right-handed men were included in this pilot study. HF-rTMS was delivered over the right M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105-120% of the individual resting motor threshold (RMT). To assess safety, electromyography (EMG) was monitored to control for signs of spread of excitation and brief EMG burst (BEB) after stimulation. Additionally, TMS side effects questionnaires and the numeric rating scale (NRS) were administered during each session. We assessed corticospinal excitability (CSE) and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and box and blocks test (BBT) scores, respectively. Overall, the sessions were tolerated and feasible without any pain development. However, EMG analysis during 15 Hz rTMS administration revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between 15 Hz rTMS SI and rMEP increase. No significant changes were highlighted for motor performance measures. Although feasible and tolerable by the AB individuals tested, the results demonstrate that when administered at suprathreshold intensities (≥ 105% RMT) the 15 Hz rTMS protocol reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such combinations of high-intensity and high-frequency stimulation protocols. The results also give insight into the nonlinear existent relationship between the SI and HF-rTMS effects on CSE.NEW & NOTEWORTHY The results of this pilot study show the effects of a therapeutically promising 15 Hz repetitive transcranial magnetic stimulation (rTMS) protocol, administered at different suprathreshold intensities in able-bodied individuals. Although tolerable and feasible with a neuromodulatory potential, 15 Hz rTMS might result in persistent excitability that needs to be closely monitored if administered at suprathreshold stimulation intensity. These results reaffirm the importance of feasibility studies, especially in translational animal-to-human research.

Adapting Stanford Neuromodulation Therapy (SNT) for clinical feasibility: Rationale and results of a small case series

• Novel rTMS protocols have achieved superior results for refractory depression • However, high operational cost may deter clinical applicability • An adaptation of the Stanford Neuromodulation Therapy protocol is proposed • In a short case series, the adapted protocol was feasible, safe and tolerable • Response was achieved in 3/4 and remission in 2/4 patients Developments regarding technical aspects of repetitive Transcranial Magnetic Stimulation (rTMS) have been linked to better results in medication-resistant depression treatment. An intermittent theta-burst (iTBS) rTMS protocol optimized for these findings, namely the Stanford Neuromodulation Therapy, has in fact shown encouraging results in trials. Nonetheless, higher operational costs and reduced feasibility in average clinical settings may deter its applicability and overall reproducibility. Particularly, the need for personalized functional connectivity studies for neuronavigation guidance and greater logistic and patient-related requirements for conducting 10 daily sessions may be challenging. We report the results of an adapted accelerated iTBS protocol with fewer daily sessions and simpler target obtention method. Four patients in a severe, refractory depressive episode received five daily iTBS sessions (1800 pulses/session) spaced by 50 minutes, five days a week, for two weeks. Neuronavigated coil positioning used individualized neuroanatomic space but was targeted at a previously reported population-based left dorsolateral prefrontal–subgenual cingulate cortex peak anticorrelation coordinate (−38, 44, 26). Assessments were performed at baseline, at the end of 50 sessions and at two-week follow-up. At follow-up, three patients were responders and two had reached remission. Considering the whole sample, depression measures showed a 56.9% reduction, with a median decrease of 14.5 points on the PHQ-9. Uncontrolled study with a very small sample and short follow up time. The proposed intervention was feasible in a clinical practice setting, being well tolerated by patients and achieving a 3/4 response and 2/4 remission rates.

Treating Spindling Excessive Beta with Inhibitory rTMS: A Case Study

The present case report investigated whether 1 Hz repetitive transcranial magnetic stimulation (rTMS) could reduce the symptoms and electrophysiological variables associated with spindling excessive beta (SEB) located in the frontal lobes. A 9-year-old patient who displayed emotional reactivity and impulsivity was evaluated using a computerized assessment of cognitive functioning and a quantitative electroencephalogram (qEEG) which displayed SEB. The patient was treated for 5 days with a 1 Hz rTMS protocol using a deep TMS coil. Improvements in both electrical power and cognitive measures were observed after a post qEEG. This report concludes that more research is needed to evince that inhibitory rTMS can reduce power in SEB and improve symptoms of over arousal.

Repetitive transcranial magnetic stimulation in patients with fibromyalgia: A protocol for systematic review and network meta-analysis.

Fibromyalgia is a chronic disease characterized by widespread pain. Repetitive transcranial magnetic stimulation (rTMS) effectively relieves pain intensity in patients with fibromyalgia. The frequency and target site of rTMS have significant roles in therapy effectiveness. However, there is disagreement over the best rTMS protocol. Thus, we will conduct a thorough systematic review and network meta-analysis to rank the efficacy of these various rTMS protocols and determine which is most beneficial in lowering pain and enhancing the quality of life. Databases PubMed, Web of Science, Embase, and Cochrane Library will be searched for clinical randomized controlled trials of rTMS in fibromyalgia. The retrieval time is from the inception of the database until October 1, 2022. Following the Cochrane Handbook, 2 reviewers will independently review the literature, extract data, and evaluate the risk of bias of included articles. Pain intensity and quality of daily life are outcome indicators. Stata 17.0 and ADDIS 1.16.8 software will be used for pairwise meta-analysis and network analysis to evaluate the effectiveness of rTMS and the ranking probability of all protocols. The recommended grading assessment, development, and evaluation will be used to assess the overall quality of the evidence. The meta-analysis and probability ranking of the network determined the best TMS protocol for fibromyalgia. This study will provide systematic support of evidence-based medicine for TMS in fibromyalgia, integrate the results of direct and indirect comparisons of the efficacy of different rTMS protocol, and provide the best one.

Influence of High-Frequency Repetitive Transcranial Magnetic Stimulation on Neurobehavioral and Electrophysiology in Patients with Disorders of Consciousness.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DOC). However, its therapeutic effects in the literature are inconsistently documented. The primary aim of this study was to explore the alterations in neural connectivity and neurobehavioral reactivity during rTMS modulation in patients with DOC. In addition, safety was investigated as a secondary aim. The presence of bilateral N20 components in DOC patients was determined by somatosensory-evoked potential (SEP) before enrollment in the study. A total of 64 patients were enrolled and randomly placed into the active and sham groups. Ultimately, 50 patients completed the study. Twenty-five patients in the active group underwent real HF-rTMS, and 25 patients in the sham group underwent sham HF-rTMS, which was delivered over the left dorsolateral prefrontal cortex (DLPFC). The outcome measures of performed pre- and postintervention included the latencies of the N20 and N20-P25 amplitudes of SEP, brainstem auditory-evoked potential (BAEP) grade, JFK Coma Recovery Scale-Revised (CRS-R) score, and Glasgow Coma Scale (GCS) score; any adverse events were recorded at any time during the intervention. Following six weeks of treatment, a significant increase was observed in the total CRS-R and GCS scores, and the N20-P25 amplitudes of patients in the two groups were compared with that obtained from preintervention (all p values < 0.05). The waves of BAEP in the two groups also showed a trend toward normalized activity compared with preintervention grades (p values < 0.05). A significant decrease in the latencies of N20 (p values < 0.001) was observed in the active group compared with measurements obtained from preintervention, whereas no significant decrease was observed in the sham group (p values = 0.013). The improvement in total CRS-R scores (p values = 0.002), total GCS scores (p values = 0.023), and N20-P25 amplitudes (p values = 0.011) as well as the decrease in latencies of N20 (p values = 0.018) and change in BAEP grades (p values = 0.013) were significantly different between the two groups. The parameters in neural connectivity (N20-P25 amplitudes, N20 latencies, and BAEP grades) were significantly correlated with the total CRS-R and GCS scores at postintervention, and the changes of CRS-R before and after interventions have a positive relationship with N20-P25 amplitudes. No adverse events related to the rTMS protocol were recorded. Neural connectivity levels are affected by HF-rTMS and are significantly related to clinical responses in DOC patients with the presence of bilateral N20. The elevation of neural connectivity levels may lay a foundation for successful HF-rTMS treatment for DOC patients.

Sleep predicts the response to rTMS and CBT in patients with OCD: an open label effectiveness study

BackgroundAlthough many OCD patients benefit from repetitive transcranial magnetic stimulation (rTMS) as treatment, there is still a large group failing to achieve satisfactory response. Sleep problems have been considered transdiagnostic risk factors for psychiatric disorders, and prior work has shown comorbid sleep problems in OCD to be associated with non-response to rTMS in OCD. We therefore set out to investigate the utility of sleep problems in predicting response to rTMS in treatment resistant OCD. MethodA sample of 61 patients (treated with 1-Hz SMA or sequential 1-Hz SMA+DLPFC rTMS, combined with cognitive behavioral therapy) were included. Sleep disturbances were measured using the PSQI, HSDQ and actigraphy. Treatment response was defined as a decrease of at least 35% in symptom severity as measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results32 of 61 patients (52.5%) responded to rTMS, and trajectories of response were similar for both rTMS protocols. Three PSQI items (Subjective Sleep Quality; Sleep Latency and Daytime Dysfunction) and the HSDQ-insomnia scale were found to predict TMS response. A discriminant model yielded a significant model, with an area under the curve of 0.813. ConclusionFuture replication of these predictors could aid in a more personalized treatment for OCD.

Role of maintenance treatment on long-term efficacy of bilateral iTBS of the prefrontal cortex in treatment-seeking cocaine addicts: A retrospective analysis.

CUD, like other addictions, is a chronic disease characterized by a high rate of relapse and drop-out (DO) from medical and behavioral treatment programs, which is positively correlated with relapse. Repetitive transcranial Magnetic Stimulation (rTMS) protocols have shown therapeutic potential in addiction in the short term, but only a few studies have explored their long-term efficacy, so far. This study explores the long-term outcome of bilateral intermittent theta-burst stimulation (iTBS) of the prefrontal cortex (PFC) in cocaine use disorder (CUD) and the possible influence of maintenance treatment in improving abstinence and decreasing DO rates. Eighty-nine treatment-seeking CUD patients were exposed to 20 sessions of iTBS. At the end of the treatment 61 (81%) abstinent patients underwent a 12 months follow-up. Among these, 27 patients chose to follow a maintenance treatment (M), whereas 34 patients chose not to adhere to a maintenance treatment (NM). Overall, among patients reaching the 12 months follow-up endpoint, 69.7% were still abstinent and 30.3% relapsed. In NM-patients the DO rate was significantly higher than in M-ones (58.82 vs. 29.63%). The present observations show the long-term therapeutic effect of bilateral PFC iTBS to decrease cocaine consumption. Moreover, they underline the importance to perform a maintenance protocol to consolidate abstinence and decrease DO rates over time.

Prognostic factors in major depressive disorder: comparing responders and non-responders to Repetitive Transcranial Magnetic Stimulation (rTMS), a naturalistic retrospective chart review.

Repetitive transcranial magnetic stimulation (rTMS) is widely utilized as an effective treatment for major depressive disorder (MDD) with varying response rates. Factors associated with better treatment outcome remain scarce. This naturalistic retrospective chart review hopes to shed light on easily obtainable and measurable predictive factors for patients referred to rTMS. Protocol parameters, medication, rated scales, rTMS protocols, and treatment outcomes were reviewed for 196 patients with MDD who received rTMS at Saint Boniface Hospital between 2013 and 2019. Logistic regression and marginal effects were used to assess the different predictor variables for response (50% reduction or more on the Hamilton Depression Rating Scale (Ham-D)) and remission (Ham-D of ≤7 by the last session). HamD at 10 sessions was predictive of remission, and Sheehan Disability Scale (SDS) at 10 sessions was predictive of response to rTMS. Ham-D, SDS, and Beck Anxiety Inventory were predictive of remission and response by Beck Anxiety Inventory 20 sessions. High frequency rTMS had a similar response and remission rate to low frequency, but higher response rate to intermittent Theta Burst Stimulation with no difference in remission rate. Positive predictive factors of response were lower age and bupropion use. Negative predictive factors were antipsychotics, anticonvulsants, or benzodiazepine use. For remission, antipsychotics or anticonvulsants use were negative predictors; bupropion use and higher resting motor threshold were positive predictors. Severity of depression as measured by baseline HamD was not associated with different probabilities of treatment success.

Effective corticospinal excitability neuromodulation elicited by short-duration concurrent and synchronized associative cortical and neuromuscular stimulations

Optimal parameters of combined repetitive associative transcranial magnetic stimulation (rTMS) and neuromuscular electrical stimulation (NMES) for neuromodulation of central nervous system (CNS) excitability are not well understood. We examined corticospinal excitability after short-duration concurrent and synchronized associative stimulation applied using primary motor cortex rTMS and upper-limb NMES. Intermittent theta burst stimulation (iTBS) was delivered with burst at 50 Hz and repeated at 5 Hz over the course of 192 s as an established cortical facilitation rTMS protocol. NMES was applied to activate the extensor carpi radialis muscle over the same 192 s duration. Four interventions were compared: (1) iTBS with concurrent and synchronized 50 Hz NMES; (2) iTBS with concurrent and synchronized 5 Hz NMES; (3) iTBS with concurrent and asynchronized 41 Hz NMES; (4) iTBS with 5 s delayed and synchronized 50 Hz NMES. Single-pulse motor evoked potential (MEP) responses elicited by transcranial magnetic stimulation of the primary motor cortex and maximum motor responses (Mmax) elicited by radial nerve stimulation were compared before and for 30 min after each intervention. Our results showed that corticospinal excitability (MEP/Mmax) was only facilitated after the iTBS and concurrent 50 Hz NMES intervention, but the responses returned to baseline within 10 min of completing the intervention. This result demonstrates that short-duration concurrent and synchronized stimulation could be applied to effectively neuromodulate corticospinal excitability. Therefore, repetitive synchronized associative stimulation of the primary motor cortical networks and sensorimotor peripheral circuits may be enhanced using synchronized 50 Hz frequency of activation during concurrent stimulation.

Assessing the mechanisms of brain plasticity by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a non-invasive technique for focal brain stimulation based on electromagnetic induction where a fluctuating magnetic field induces a small intracranial electric current in the brain. For more than 35 years, TMS has shown promise in the diagnosis and treatment of neurological and psychiatric disorders in adults. In this review, we provide a brief introduction to the TMS technique with a focus on repetitive TMS (rTMS) protocols, particularly theta-burst stimulation (TBS), and relevant rTMS-derived metrics of brain plasticity. We then discuss the TMS-EEG technique, the use of neuronavigation in TMS, the neural substrate of TBS measures of plasticity, the inter- and intraindividual variability of those measures, effects of age and genetic factors on TBS aftereffects, and then summarize alterations of TMS-TBS measures of plasticity in major neurological and psychiatric disorders including autism spectrum disorder, schizophrenia, depression, traumatic brain injury, Alzheimer's disease, and diabetes. Finally, we discuss the translational studies of TMS-TBS measures of plasticity and their therapeutic implications.

PO080 / #705 NOVEL MULTI-TARGET REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION PROTOCOL FOR THE TREATMENT OF COMORBID DEPRESSION AND CHRONIC PAIN: E-POSTER VIEWING

Major Depressive Disorder (MDD) and chronic pain are frequently co-occurring, and the onset of either condition can either precede or follow the onset of the other. Notably, clinical outcome for pharmacological and rTMS treatment for depression is significantly worse in the presence of chronic pain symptoms. To improve clinical care for depression it is thus critical to address the comorbidity of depression and chronic pain in a unified approach rather than treating them as separate conditions. We examined whether an open label multi-target rTMS protocol including stimulation of the left dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1), the most effective rTMS target for pain, would improve depressive and chronic pain symptoms more than a single target DLPFC stimulation.

24.1 Is Repetitive Transcranial Magnetic Stimulation (rTMS) Ready for Clinical Use as a Treatment Tool for Mental Health Targets in Children and Youth With ASD?

ObjectivesRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation tool with potential for broad application in individuals with neuropsychiatric conditions.MethodsBased on a narrative review and editorial that will be published in spring 2022, a limited number of rTMS studies have been conducted in children and youth with other primary diagnoses, including ASD.ResultsThree published rTMS studies have used a rigorous RCT design in individuals with ASD. Much of the available rTMS research in ASD uses inhibitory rTMS protocols to enhance inhibitory function, which is hypothesized to be impaired in ASD. The efficacy of rTMS in treating youth with ASD is currently inconclusive due to the heterogeneity of the treatment protocols and outcomes measured, as well as limited studies designed with a proper blinded, sham-controlled group. However, a handful of studies show that rTMS treatments may reduce repetitive behavior, improve executive functioning, and support enhanced social interaction, with only mild adverse events such as transient headaches or scalp discomfort.ConclusionsResults point to the need for a more robust body of evidence to identify the potential benefit of treating youth with ASD through rTMS, along with the optimal protocols.ASD, ND, NM ObjectivesRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation tool with potential for broad application in individuals with neuropsychiatric conditions. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation tool with potential for broad application in individuals with neuropsychiatric conditions. MethodsBased on a narrative review and editorial that will be published in spring 2022, a limited number of rTMS studies have been conducted in children and youth with other primary diagnoses, including ASD. Based on a narrative review and editorial that will be published in spring 2022, a limited number of rTMS studies have been conducted in children and youth with other primary diagnoses, including ASD. ResultsThree published rTMS studies have used a rigorous RCT design in individuals with ASD. Much of the available rTMS research in ASD uses inhibitory rTMS protocols to enhance inhibitory function, which is hypothesized to be impaired in ASD. The efficacy of rTMS in treating youth with ASD is currently inconclusive due to the heterogeneity of the treatment protocols and outcomes measured, as well as limited studies designed with a proper blinded, sham-controlled group. However, a handful of studies show that rTMS treatments may reduce repetitive behavior, improve executive functioning, and support enhanced social interaction, with only mild adverse events such as transient headaches or scalp discomfort. Three published rTMS studies have used a rigorous RCT design in individuals with ASD. Much of the available rTMS research in ASD uses inhibitory rTMS protocols to enhance inhibitory function, which is hypothesized to be impaired in ASD. The efficacy of rTMS in treating youth with ASD is currently inconclusive due to the heterogeneity of the treatment protocols and outcomes measured, as well as limited studies designed with a proper blinded, sham-controlled group. However, a handful of studies show that rTMS treatments may reduce repetitive behavior, improve executive functioning, and support enhanced social interaction, with only mild adverse events such as transient headaches or scalp discomfort. ConclusionsResults point to the need for a more robust body of evidence to identify the potential benefit of treating youth with ASD through rTMS, along with the optimal protocols.ASD, ND, NM Results point to the need for a more robust body of evidence to identify the potential benefit of treating youth with ASD through rTMS, along with the optimal protocols.

A New Treatment Protocol of Combined High-Dose Levothyroxine and Repetitive Transcranial Magnetic Stimulation for the Treatment of Rapid-Cycling Bipolar Spectrum Disorders: A Cohort Evaluation of 55 Patients.

Background: Bipolar spectrum disorders (BSD) are highly disabling, with rapid cycling being treatment resistant. High-dose levothyroxine (HDT) has been reported to be effective. Diagnosis is associated with mutations in thyroid-activating enzymes and cerebral transporter protein carrier. Repetitive transcranial magnetic stimulation (rTMS) has neuroplastic effects. Methods: We report data on 55 severely symptomatic patients with rapid-cycling BSD treated with a combination protocol of HDT and rTMS. Of the patients, 31 patients (56.4%) were female and 40 (72.7%) had at least one additional diagnosis. Results: Patients were evaluated at three monthly intervals after acute treatment. Remission was measured using the Sheehan Disability Scale (SDS). The average number of medications prescribed was 1.8, with 32 patients (58.2%) needing only levothyroxine. The average dose of levothyroxine was 303.7 mcg (50 mcg–1000 mcg). A total of 53 patients were in remission (96.4%), with an average duration of 2.0 years. The SDS scores decreased significantly (Cohen’s d = 2.61 (95% C.I. 1.81 to 2.83, p < 0.001). One patient had reversible side effects. A total of 52 (94.3%) patients had Deiodinase 1 and 2 (DiO1/DiO2) or SLCO1C1 protein carrier gene mutations. Conclusion: The data support the safety and acceptability of combined HDT/rTMS. Patients achieved long remissions with substantial improvements in quality of life.

A Different rTMS Protocol for a Different Type of Depression: 20.000 rTMS Pulses for the Treatment of Bipolar Depression Type II

In this open-label naturalistic study, we assess the feasibility, tolerability, and effectiveness of a repetitive transcranial magnetic stimulation protocol with a reduced total pulse number for treating patients suffering from bipolar disorder type II. All patients received one rTMS treatment session of 1000 pulses for 20 consecutive working days, accumulating to 20.000 rTMS pulses applied over 4 weeks. We measured the patients’ symptoms before the start, halfway through, directly after, and one month after treatment. We quantified the depression symptoms using both the Beck depression inventory scale and the symptom checklist-90 depression subscale. Patients showed a significant reduction in depression symptoms directly after treatment and an even further reduction one month after treatment. The remission rates were at 26% halfway through treatment (after the 10th session), 61% directly after treatment (after the 20th session), and increased to 78% at the 1-month follow-up. Importantly, the protocol proved to be feasible and highly tolerable in this patient population, with no adverse effects being reported. Considering these positive results, further research should focus on replicating these findings in larger clinical samples with control groups and longer follow-up periods, while potentially adding maintenance sessions to optimize the treatment effect and stability for bipolar disorder type II patients.