rTMS For Major Depression Research Articles

A randomized sham-controlled trial of high-dosage accelerated intermittent theta burst rTMS in major depression: study protocol

BackgroundIntermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), can be administered in 1/10th of the time of standard rTMS (~ 3 min vs. 37.5 min) yet achieves similar outcomes in depression. The brief nature of the iTBS protocol allows for the administration of multiple iTBS sessions per day, thus reducing the overall course length to days rather than weeks. This study aims to compare the efficacy and tolerability of active versus sham iTBS using an accelerated regimen in patients with treatment-resistant depression (TRD). As a secondary objective, we aim to assess the safety, tolerability, and treatment response to open-label low-frequency right-sided (1 Hz) stimulation using an accelerated regimen in those who do not respond to the initial week of treatment.MethodsOver three years, approximately 230 outpatients at the Centre for Addiction and Mental Health and University of British Columbia Hospital, meeting diagnostic criteria for unipolar MDD, will be recruited and randomized to a triple blind sham-controlled trial. Patients will receive five consecutive days of active or sham iTBS, administered eight times daily at 1-hour intervals, with each session delivering 600 pulses of iTBS. Those who have not achieved response by the week four follow-up visit will be offered a second course of treatment, regardless of whether they initially received active or sham stimulation.DiscussionBroader implementation of conventional iTBS is limited by the logistical demands of the current standard course consisting of 4–6 weeks of daily treatment. If our proposed accelerated iTBS protocol enables patients to achieve remission more rapidly, this would offer major benefits in terms of cost and capacity as well as the time required to achieve clinical response.Trial registrationClinicalTrials.gov Identifier: NCT04255784.

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.

Challenge to appropriate use of rTMS for major depression in Japan

Challenge to appropriate use of rTMS for major depression in Japan

Personality Trait Predictive Utility and Stability in Transcranial Magnetic Stimulation (rTMS) for Major Depression: Dissociation of Neuroticism and Self-Criticism: Utilité prédictive et stabilité des traits de personnalité dans la stimulation magnétique transcrânienne répétitive (SMTr) pour la dépression majeure : dissociation du neuroticisme et de l’autocritique

Background: Cost-efficient and non-invasive predictors of antidepressant response to repetitive transcranial magnetic stimulation (rTMS) are required. The personality vulnerabilities—neuroticism and self-criticism—are associated with antidepressant outcomes in other modalities; however, self-criticism has not been examined in response to rTMS, and the literature on neuroticism and rTMS is inconsistent. Methods: This naturalistic, 4-week study involved daily dorsolateral prefrontal cortex (DLFPC) rTMS for major depression (15 unipolar, 2 bipolar). Participants completed the Big Five Inventory (neuroticism) and the Depressive Experiences Questionnaire (self-criticism) at baseline and at the end of treatment. Changes in depressive symptoms, as rated by the clinician, were quantified using the 21-item Hamilton Depression Rating Scale. Given the inconsistencies in data regarding the stability of neuroticism in patients receiving rTMS, we performed a systematic review and quantitative meta-analysis of trials examining rTMS and neuroticism. Results: rTMS significantly improved depressive symptoms, and this was predicted by higher levels of self-criticism but not neuroticism. Self-criticism was stable over the 4 weeks of rTMS; however, neuroticism decreased, and this was not related to decreases in depressive symptoms. Our quantitative meta-analysis of 4 rTMS trials in major depression ( n = 52 patients) revealed decreases in neuroticism, with a moderate effect size. Limitations: Our results are limited by a small sample size, and the absence of a sham-rTMS group. Our meta-analysis included only 4 trials. Conclusion: Highly self-critical patients appear to benefit more from rTMS than less self-critical patients. Neuroticism, a conceptually similar but distinct personality domain, does not appear to predict antidepressant response, yet this vulnerability factor for depression decreases after rTMS.

Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics. This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics. Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory. Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.

Challenge to appropriate use of rTMS for major depression in Japan

Challenge to appropriate use of rTMS for major depression in Japan

RTMS for major depression: Treatment outcomes at an academic medical center

rTMS for major depression: Treatment outcomes at an academic medical center

Number of pulses or number of sessions? An open-label study of trajectories of improvement for once-vs. twice-daily dorsomedial prefrontal rTMS in major depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) shows efficacy in the treatment of major depressive episodes (MDEs), but can require ≥4–6 weeks for maximal effect. Recent studies suggest that multiple daily sessions of rTMS can accelerate response without reducing therapeutic efficacy. However, it is unresolved whether therapeutic effects track cumulative number of pulses, or cumulative number of sessions. ObjectiveThis open-label study reviewed clinical outcomes over a 20–30 session course of high-frequency bilateral dorsomedial prefrontal cortex (DMPFC)-rTMS among patients receiving 6000 pulses/day delivered either in twice-daily sessions 80 min apart (at 20 Hz) or single, longer, once-daily sessions (at 10 Hz). MethodsA retrospective chart review identified 130 MDD patients who underwent 20–30 daily sessions of bilateral DMPFC-rTMS (Once-daily, n = 65; Twice-daily, n = 65) at a single Canadian clinic. ResultsMixed-effects modeling revealed significantly faster improvement (group-by-time interaction) for twice-daily versus once-daily DMPFC-rTMS. Across both groups, the pace of improvement showed a consistent relationship with number of cumulative sessions, but not with cumulative number of pulses. Although the twice-daily group completed treatment in half as many days, final clinical outcomes did not differ significantly between groups on dichotomous measures (response/remission rates: once-daily, 35.4%/33.8%; twice-daily, 41.5%/35.4%), or continuous measures, or on overall response distribution. ConclusionsTwice-daily rTMS appears feasible, tolerable, and capable of achieving comparable results to once-daily rTMS, while also reducing course length approximately twofold. Therapeutic gains tracked the cumulative number of sessions, not pulses. Future randomized studies comparing once-daily to multiple-daily rTMS sessions, while controlling for number of pulses, may be warranted.

Brain influences of accelerated rTMS in major depression

Brain influences of accelerated rTMS in major depression

Number of pulses or number of sessions? Trajectories of improvement for once-daily vs. twice-daily dorsomedial prefrontal rTMS in major depression

Number of pulses or number of sessions? Trajectories of improvement for once-daily vs. twice-daily dorsomedial prefrontal rTMS in major depression

Increase of sleep spindle density induced by rTMS for major depression

Increase of sleep spindle density induced by rTMS for major depression

Safety, feasibility, and efficacy of rTMS for major depression in borderline personality disorder: A 2-case report

Safety, feasibility, and efficacy of rTMS for major depression in borderline personality disorder: A 2-case report

Transcranialis mágneses stimuláció terápiás alkalmazása major depresszióban

[The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention.]

Neuroplasticity possibly induced by a series of prefrontal rTMS for major depression

Neuroplasticity possibly induced by a series of prefrontal rTMS for major depression

Resting-state functional connectivity to subgenual cingulate cortex differentially predicts treatment response for 10 Hz versus intermittent theta-burst rTMS in major depression

s / Brain Stimulation 8 (2015) 395e411 396 included age, gender, years with disease, doses of L-DOPA, dyskinesias, stadium by Hoehn and Yahr. rTMS was performed with a Magstim Rapid2, 5 consecutive days, for 3 months, resting 3 weeks per month, 100 pulses, 25 Hz, 80% of motor threshold. Results: We recruited a total of 2 men and 2 women, stadium Hoehn and Yahr 1.5-3, age 67 8. 76, 7.75 2. 5 years with PD, basal doses of L-dopa 850 270.80 with dyskinesias type 3 in 3 patients and basal UPDR of 53 26.99. After the third week of rTMS, patients were able to score by UPDRS 40.75 20.23, and revealed a dose reduction in L-DOPA of 578.12 93.74. Conclusions: According with the clinical features of our patients, the predominant type of dyskinesias is type 3. Preliminary results in response to rTMS treatment showa reduction in the UPDRS scale, as well as a decrease in L-DOPA dosage, which could be reduced monthly in all 4 patients.

Dorsomedial prefrontal rTMS for major depression: safety, tolerability, and effectiveness for 10 Hz versus iTBS 185 in consecutive cases

Dorsomedial prefrontal rTMS for major depression: safety, tolerability, and effectiveness for 10 Hz versus iTBS 185 in consecutive cases

Identifying brain imaging correlates of clinical response to repetitive transcranial magnetic stimulation (rTMS) in major depression

BackgroundPartial response and non-response to treatments are common problems in major depression. The identification of biological markers of clinical response may be of special interest for some adjunctive treatments, such as repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve their cost-effectiveness. ObjectiveTo identify pre-treatment functional imaging correlates of clinical response to rTMS in major depression. MethodsWe evaluated 21 depressed patients. They were randomized to receive 15 sessions of active or sham rTMS on the left dorsolateral prefrontal cortex. Functional magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain activity evoked by a word generation task. These regional activations were correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D) reduction between baseline and end of treatment. A group of 13 healthy controls was also assessed using the same fMRI protocol to obtain reference imaging measurements. ResultsAt the end of treatment, the percentage of patients with a HAM-D reduction greater than 50% was larger in the active than in the sham rTMS group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were significantly correlated with smaller deactivations during pre-treatment fMRI assessment in the anterior cingulate, the left medial orbitofrontal and the right middle frontal cortices, in addition to larger activations in the left ventral-caudal putamen. ConclusionsThese results suggest that brain activity in regions arguably relevant for major depression may predict clinical response to rTMS. This approach may help in identifying the most suitable candidates to undergo rTMS treatment.

Stimulation magnétique transcrânienne répétée dans la prise en charge des épisodes dépressifs majeurs : facteurs prédictifs de réponse thérapeutique

Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique that has been investigated as a novel treatment for psychiatric disorders, notably in major depression, and has shown statistically significant effects. The authors found it necessary to propose an up-to-date review of positive predictors for antidepressive response to repetitive transcranial magnetic stimulation. Based on an exhaustive consultation of Medline data, supplemented by a manual research, only works evaluating response factors of rTMS in major depression were retained. Twenty-nine studies were retained, including meta-analyses, reviews, randomized controlled trials and open trials. The most concordant data clearly indicate that a high score of treatment resistance, a long duration of current episode, advanced age, and psychotic symptoms are negative predictors for treatment response to rTMS. In the older patients, menopausal women are especially concerned. However, some parameters should be adapted to the degree of cortical atrophy such as intensity of stimulation or total number of rTMS sessions. Previous response to rTMS therapy seems to be a good predictor contrary to non-response to electroconvulsive therapy. Adjunctive antidepressant treatment shows greater responsiveness to rTMS contrary to benzodiazepine or anticonvulsant treatment. To our knowledge, no study compares unipolar and bipolar depression, the profile of depression is not established yet. Imaging studies show that TMS antidepressant responders differed from non-responders in inferior frontal activity, at baseline, and even more so following treatment. Furthermore, reduced baseline cerebral metabolism in cerebellar, temporal, anterior cingulate and occipital regions of the brain was correlated with improvement after two weeks of fast (20Hz) left dorsolateral prefrontal cortex (DLPFC) rTMS. Additionally, a right frontal region emerges with divergent polarity in the metabolic prediction of response to low rTMS. Inhibiting right DLPFC or stimulating DLPFC shows similar results, the choice on the side of stimulation does not seem determining. Bilateral stimulation for the moment does not seem superior to unilateral stimulation. Parameters of stimulation associated with effectiveness of rTMS are an intensity of stimulation higher than 100% of the motor threshold, a number of stimulations per sessions superior to 1000, and a full number of days of treatment greater than 10. Parameters of stimulation must be adapted according to the treated patients. For example, older patients who present cortical atrophy need higher intensity of stimulation. Other criteria could influence effectiveness of rTMS in the same way. Would it be necessary, for example, to adapt the duration or the intensity of stimulation according to the severity of the depressive episode or its duration of evolution? Do antecedents of resistance to a pharmacological treatment oblige us to stimulate differently? Few studies exceed 10 days of treatment; will longer duration of treatment be more effective? Also, we did not find any data on the interest of maintenance treatment among responders. Should the characteristics of the depressive disorder or its evolution require maintenance treatment? What will be its rhythm and its duration? Should we adapt rTMS parameters to abnormalities highlighted by functional neuroimagery? The prospects for work remain numerous.

Acute prefrontal cortex TMS in healthy volunteers: Effects on brain 11C-αMtrp trapping

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) is a technique with purported efficacy as a treatment for major depression. Here, we assessed in vivo, in healthy volunteers, the effect of acute rTMS of the LDLPFC, relative to the stimulation of the left occipital cortex (LOC), on brain regional serotonin synthesis capacity, using the [(11)C]-alpha-methyl-tryptophan ((11)C-alphaMtrp)/PET method. Ten subjects were studied twice, once following rTMS of the LDLPFC and once following rTMS of the LOC in a randomized counterbalanced order. Three blocks of 15 trains of 10 Hz rTMS were delivered 10 min apart. Behavioural and autonomic measures were recorded before and after each rTMS session. Comparisons of TMS-related changes in regional normalized brain uptake and trapping of (11)C-alphaMtrp (K*) values were carried out using SPM99. Statistically significant regional differences were identified on the basis of an extent threshold of 50 voxels, with a peak threshold of p=0.005 uncorrected. Behavioural and autonomic measures were unaffected by rTMS. Relative to LOC stimulation, LDLPFC rTMS was associated with marked changes in normalized K* in limbic areas, with significantly lower values in the left parahippocampal gyrus (BA 28) and the right insula (BA 13), and higher values in the right cingulate gyrus (BA 31) and cuneus (BA 18). These findings indicate that acute rTMS of the LDLPFC in healthy volunteers modulates aspects of tryptophan/5-HT metabolism in limbic areas. Such adaptive changes may contribute to the mechanism of action of prefrontal rTMS in major depression.

A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression

Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have mostly involved once-daily treatment, with positive but modest clinical results. This study tested the efficacy and safety of twice-daily rTMS over 2 weeks. Thirty-eight depressed subjects enrolled in a double-blind, sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110% intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological functioning were assessed weekly by blind raters, using the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton Rating Scale for Depression (HRSD) and self-report measures. After the blind period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS. Subjects were moderately treatment resistant. Active treatment resulted in significantly greater improvement than sham over the 2-week blind period on one outcome measure only (MADRS p<0.05). Subjects showed further improvement over the 6 weeks of active rTMS. Neuropsychological test scores did not change significantly. rTMS given twice daily was effective and safe, with no adverse neuropsychological effects.