Factors That Influence Patients' Decisions About Repetitive Transcranial Magnetic Stimulation as a Treatment Option for Treatment-Resistant Depression: Protocol for a Prospective Mixed Methods Cohort Study.

Changes in Regional Cerebral Blood Flow After Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression

BackgroundCognitive behavioral therapy (CBT) and pharmacotherapy have been shown to be effective for depression, but inflexible cognition makes it difficult to introduce these therapies, and even when treated with CBT, cognitive change is not achieved, and medication adherence is likely to be inadequate. This is thought to be related to a lack of cognitive flexibility, which is defined as the ability to rapidly change behavior in the face of changing circumstances. On the other hand, transcranial magnetic stimulation (TMS) has not only the efficacy for depression but also the potential to improve cognitive flexibility. By clarifying the effects of TMS on cognitive flexibility, we can develop new treatment and methods to maximize the effectiveness of CBT and pharmacotherapy.Aims & ObjectivesThe main objective of this study is to clarify the impact of TMS on cognitive flexibility by comparing the results of psychological tests before and after TMS.MethodThe subjects were patients with major depressive disorder who had undergone TMS at University Hospital, Kyoto Prefectural University of Medicine. The Japanese version of the cognitive flexibility scale (CFS-J) was used as a quantitative measure of cognitive flexibility and the primary outcome was the change in CFS-J scores before and after the TMS course. Other information such as age, gender, and changes in Hamilton Rating Scale for Depression (HAM-D) were also collected. They received TMS treatments for 1 session per day and 5 days per week for a total of 30 sessions based on protocols covered by insurance in Japan. Each treatment included 3000 pulses at 10 Hz and 100–120% motor threshold, and the stimulation lasted for 4 seconds, followed by a 26-34 seconds stimulation interval. To evaluate the change in scores from baseline to the end of the TMS course paired samples t-tests were performed for the CFS-J. The study was reviewed and approved by the Institutional Review Board of the Kyoto Prefectural University of Medicine.ResultsData were collected from 3 subjects (2 males and 1 female), with a mean age of 71 years. The mean CFS-J before TMS was 40.3 and after TMS was 51.3; CFS-J scores were improved with TMS (p = 0.069). Meanwhile, the mean pre-TMS HAM-D score was 17.7 and post-TMS was 10; HAM-D scores were improved (p = 0.063).Discussion & ConclusionThis study quantitatively demonstrated that TMS enhanced cognitive flexibility, but did not show statistically significant differences. Due to the small sample size of this preliminary report, we will continue to accumulate data and examine changes in the CFS-J before and after TMS, as well as the relationship between various factors and cognitive flexibility, including the rate of improvement in depressive symptoms. Cognitive flexibility plays a significant role in depression, as studies of patients with treatment-resistant depression have reported that cognitive flexibility is a predictor of treatment response. Since cognitive flexibility contributes to the promotion of treatment efficacy, attention should be paid not only to the improvement of depressive symptoms with TMS, but also to its effect on cognitive flexibility.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

Accelerated Intermittent Theta Burst Stimulation: Expediting and Enhancing Treatment Outcomes in Treatment-Resistant Depression.

Over the past two decades, the number of somatic treatments for psychiatric disorders has expanded, leading to new insights into the complex relationship between chemical and electric transmission of signals in the brain. In this article, the authors discuss the different device-based treatments currently available in psychiatry. They review clinical indications; putative mechanism of action; efficacy and adverse effects; the results and limitations of salient clinical trials; and active areas of research into the neurobiology of device-based stimuli.

Within-Session Mood Changes From TMS in Depressed Patients

P281 Augmentative repetitive transcranial magnetic stimulation (RTMS) in highly treatment-resistant unipolar and bipolar depression – First Polish experiences

Optimally combining transcranial magnetic stimulation with antidepressants in major depressive disorder: A systematic review and Meta-analysis

BackgroundDespite its morbidity and mortality, the neurobiology of treatment-resistant depression (TRD) in adolescents and the impact of treatment on this neurobiology is poorly understood.MethodsUsing automatic segmentation in FreeSurfer, we examined brain magnetic resonance imaging baseline volumetric differences among healthy adolescents (n = 30), adolescents with major depressive disorder (MDD) (n = 19), and adolescents with TRD (n = 34) based on objective antidepressant treatment rating criteria. A pooled subsample of adolescents with TRD were treated with 6 weeks of active (n = 18) or sham (n = 7) 10-Hz transcranial magnetic stimulation (TMS) applied to the left dorsolateral prefrontal cortex. Ten of the adolescents treated with active TMS were part of an open-label trial. The other adolescents treated with active (n = 8) or sham (n = 7) were participants from a randomized controlled trial.ResultsAdolescents with TRD and adolescents with MDD had decreased total amygdala (TRD and MDD: −5%, P = .032) and caudal anterior cingulate cortex volumes (TRD: −3%, P = .030; MDD: −.03%, P = .041) compared with healthy adolescents. Six weeks of active TMS increased total amygdala volumes (+4%, P < .001) and the volume of the stimulated left dorsolateral prefrontal cortex (+.4%, P = .026) in adolescents with TRD.ConclusionsAmygdala volumes were reduced in this sample of adolescents with MDD and TRD. TMS may normalize this volumetric finding, raising the possibility that TMS has neurostructural frontolimbic effects in adolescents with TRD. TMS also appears to have positive effects proximal to the site of stimulation.

Treatments for major depression – Authors' reply

Aims: Major depressive disorder (MDD) and treatment-resistant depression (TRD) are significant public health challenges that not only severely affect quality of life but also place a substantial burden on healthcare systems. Individuals with TRD are at an increased risk of suicide, making early intervention essential.Two prominent neuromodulation treatments, electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), are commonly used in clinical practice. Despite numerous studies comparing these interventions, definitive conclusions regarding their relative efficacy in treating depression are still lacking. This systematic review aims to compare the antidepressive effects of ECT and TMS, as measured by the Hamilton Depression Rating Scale (HAM-D), whilst also evaluating their clinical feasibility, tolerability, and patient acceptability to guide evidence-based treatment decisions.Methods: A systematic literature review was conducted using the PubMed and Scopus databases, using keywords “TMS AND depression”, “ECT AND depression”, and “TMS OR ECT AND depression”. Out of 170 initially retrieved articles, six studies met the inclusion criteria of directly comparing the effects of ECT and TMS in patients diagnosed with MDD or TRD. Three other studies were also included in the analysis for their valuable insights on related outcomes.Results: The findings suggest that ECT has a superior short-term antidepressive effect compared with TMS. Specifically, ECT achieved a response rate of 64.4% and remission rate of 53%, whereas high frequency rTMS (HFrTMS) yielded response and remission rates of 48.7% and 32.2%, respectively. Low frequency rTMS (LFrTMS) demonstrated a notably lower response rate of 20%. In cases of psychotic depression, ECT led to a 58.8% reduction in HAM-D scores, whilst TMS produced a 38% reduction. However, bilateral rTMS (BL-rTMS) emerged as a promising option, offering moderate efficacy alongside superior tolerability and lower dropout rates.Conclusion: Whilst ECT remains the most effective short-term treatment for depression, its need for general anaesthesia and seizure induction may limit its acceptability. Despite being considered safe and effective by many psychiatrists, the stigma surrounding ECT creates a potential barrier to its widespread acceptance. TMS, particularly BL-rTMS, presents a less invasive alternative with better tolerability, making it a potentially reasonable option for patients and clinicians. These findings highlight the importance of personalised treatment plans that consider clinical severity, patient preference, and available resources. Future longitudinal studies are needed to assess long-term outcomes and adverse effects, such as the mild memory loss associated with ECT in the long term, to further refine the role of these neuromodulation therapies in managing MDD and TRD.

Back to table of contents Previous article Next article Clinical & ResearchFull AccessIs Magnetic Seizure Therapy Ready to Round the Corner?Nick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:25 May 2021https://doi.org/10.1176/appi.pn.2021.5.44AbstractAn ongoing phase 3 trial comparing magnetic seizure therapy with electroconvulsive therapy may finally provide the proof needed to get this promising intervention into clinical use.In May of 2000, Sarah Lisanby, M.D., then an assistant professor of psychiatry at Columbia University, was flying over to Bern, Switzerland, to test out a new tool in the fight against depression. She had spent the previous five years building and testing a device that used strong magnetic waves to stimulate controlled seizures in the brain. The hope was that this new approach to neuromodulation might provide severely depressed patients welcome relief from their symptoms without some of the risks associated with electroconvulsive therapy (ECT), which uses electricity to stimulate controlled seizures.Sarah Lisanby, M.D., prepares to administer magnetic seizure therapy to the first human volunteer in 2000.Courtesy of Sarah Lisanby, M.D.Lisanby’s colleague Thomas Schlaepfer, M.D., had identified a young woman with treatment-resistant depression who lived in Switzerland and was willing to undergo the experimental procedure. So, with a suitcase full of spare machine parts, Lisanby set out to conduct the first in-human trial of magnetic seizure therapy (MST).The results of that trial, which were published 20 years ago this spring, were promising, setting magnetic seizure therapy on a long clinical journey that may soon reach fruition.Magnetic Pulses Have AdvantagesThe research by Lisanby, now the director of the Noninvasive Neuromodulation Unit at the NIH Clinical Center, followed decades of work by others to increase options for patients with treatment-resistant depression. Lisanby is also the director of the Division of Translational Research at the National Institute of Mental Health (NIMH).“Attempts to modify how ECT is given are nearly as old as ECT itself,” she explained. By adjusting the amount of current delivered and changing where the electrodes are placed on the scalp, researchers looked for ways to increase the efficacy and reduce the side effects of ECT, including short-term memory loss. One of the most significant safety advances in ECT practice was shifting the placement of electrodes from bilateral (one on each side of the scalp) to unilateral (one on the right side and one on the center top of the head), she noted.“But physics limits how far we can advance with electric stimulation,” Lisanby said. Electrical currents meet heavy resistance and diffuse as they pass through skin and skull, thus making it difficult to target a specific region of the brain. Additionally, excess electrical energy spills out to surrounding brain regions, which leads to side effects.In contrast, magnetic waves can pass through biological tissue unimpeded.The idea of triggering brain seizures via magnetism was conceptualized in the early 1990s by Columbia’s Harold Sackeim, Ph.D., one of Lisanby’s mentors and a leading authority on ECT. At that time, a novel approach known as transcranial magnetic stimulation (TMS) was making headlines as a potential depression treatment. Though TMS relied on low-level magnetic energy to “gently” modulate brain activity, these pulses were found to induce seizures in rare instances. Sackeim reasoned that stronger magnetic pulses could induce more focalized seizures and mimic ECT’s antidepressant effects with fewer unwanted side effects.MST is not without risks, as patients who receive the procedure report transient scalp pain and headaches, said Shawn McClintock, Ph.D., an associate professor of psychiatry at the University of Texas Southwestern Medical Center (UTSW) who studies neurostimulation therapies. “But the risk of short-term amnesia and other cognitive problems that have contributed to ECT’s stigma is far less.”MST Hurdles Left to ClearIn the 21 years since Lisanby successfully treated her first patient with MST, the technology has undergone a steady if plodding progression toward clinical use. Numerous small studies, including a couple of head-to-head comparisons, have shown MST is about as effective as ECT at reducing depressive symptoms with fewer cognitive side effects. Some research centers, notably the Temerty Centre for Therapeutic Brain Intervention in Toronto, have also begun testing whether MST might be effective in patients with treatment-resistant bipolar depression or schizophrenia.Researchers at the University of Texas Southwest Medical Center demonstrate a contemporary MST device, which is believed to provide the antidepressant efficacy of electroconvulsive therapy with reduced cognitive side effects.UTSWDespite more than 20 years of positive data and the approval of TMS for treatment-resistant depression in 2008, experts say it will likely be years before MST machines appear in clinics.“MST requires a different device and uses different frequencies than TMS, so it is essentially a brand-new therapy and not a modified form of TMS,” said McLintock. “Seizure therapy is also an intensive treatment, so you want to proceed with the highest rigor, especially when it comes to safety, even if it takes more time.”Another factor contributing to delays in moving MST to the clinic is that the medical device industry has not invested in this new technology as they did with TMS, Lisanby acknowledged. Currently, only MagVenture (based in Denmark) builds MST devices, and the company does not have the capital to sponsor large, multicenter studies (though they have donated machines for clinical research).“NIMH recently stepped up to the plate and agreed to support a phase 3 trial” evaluating MST for treatment-resistant depression—a pivotal step for clinical approval, Lisanby explained. The trial is known as CREST-MST (for Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression). The multicenter trial will be led by Daniel Blumberger, M.D., the director of Toronto’s Temerty Centre, and Carol Tamminga, M.D., the Lou and Ellen McGinley Distinguished Chair and the McKenzie Chair in Psychiatry at UTSW.Comparison Trial UnderwayAs the director of the largest ECT service in Canada, Blumberger knows firsthand that ECT is the most effective treatment for severe treatment-resistant depression. He also knows it is the treatment option most refused when suggested to patients.“If we could offer patients an alternative, we could help so many more,” he said. The same belief was held by the Centre’s prior director, Jeff Daskalakis, M.D., Ph.D., who in 2011 led the effort to obtain an MST device and funding to start clinical trials in Canada.A decade later, the Temerty Centre has become a leader in clinical neuromodulation research and is a fitting choice to lead CREST-MST. Blumberger recently oversaw a head-to-head study that ultimately led to the FDA clearance of a new, rapid form of TMS known as theta-burst stimulation.The CREST-MST trial is enrolling 260 adults with treatment-resistant depression at both the Temerty Centre and UTSW and providing them with either ECT or MST in a random and blinded fashion. (Both procedures are done under anesthesia so patients are not aware of their treatment; the clinicians assessing patient recovery will also be unaware of the treatment patients are receiving.) Blumberger told Psychiatric News that the trial has two primary goals. “The intent is to see whether MST is as clinically effective as ECT in terms of depression improvement and whether it has a better cognitive side-effect profile,” he said.The trial had enrolled about 25% of participants when the COVID-19 pandemic hit last spring. Enrollment had to be put on hold as research activities and patient volumes were limited at both participating centers. Both sites have since reopened, and Blumberger is hopeful that the study can get back to full speed. He is also looking to re-launch another trial with his colleagues in Vancouver and London, Ontario, which is comparing MST and ECT for bipolar depression.“When all the data are in, I am hopeful MST will meet the bar for regulatory approval and within a few years become a new option for treatment-resistant depression and potentially other refractory psychiatric disorders,” he said.‘One Size Does Not Fit All’If MST does emerge as a safer alternative to ECT, will that spell the end for the original neuromodulation therapy?Lisanby won’t rule anything out but thinks it’s most likely that MST will become another option for patients with treatment-resistant depression rather than a replacement for ECT. She noted that despite the consensus that unilateral ECT was a tremendous advance over bilateral ECT, some patients still receive the latter procedure. “Patients who qualify for ECT have severe and treatment-resistant depression, so we want as broad a range of options as possible.”“One size does not fit all,” agreed McClintock, who will also be working on CREST-MST. “As the field advances, we may find that ECT might be better in certain cases, such as patients with psychotic symptoms or suicidal ideation. That’s why we need to find biomarkers that may suggest which treatment would work best for a given patient.”A key element of personalizing these brain stimulation procedures is to understand how they exert their effects—the mechanisms of ECT and MST are still somewhat of a black box. One of the focuses of McClintock’s research is using neurocognitive and neuroimaging tools to measure the changes in the brain after therapeutic seizures are induced. “We need to know why these treatments are doing what they are doing,” he said. ■The details of the first MST trial, “Magnetic Seizure Therapy of Major Depression,” is posted here.More information on CREST-MST is posted here. ISSUES NewArchived

Evaluating real-world effectiveness of accelerated transcranial magnetic stimulation for treatment-resistant depression in a tertiary referral center based in Quebec, Canada

Major depression is a common mental health condition and is associated with significant disease burden. Up to a third of individuals suffer from treatment resistant depression (TRD), which is a...

Objectives. Deep transcranial magnetic stimulation (DTMS) has been shown to be efficacious and relatively safe for major depressive disorder (MDD). However, its clinical utility as an augmenting strategy for treatment-resistant depression (TRD) remains unexplored. Methods. In an open label trial, 17 outpatients with severe TRD received 4 weeks of daily high frequency DTMS over the left dorsolateral prefrontal cortex. Depressive and anxious symptoms, suicidality and quality of life (QOL) were measured at baseline (i.e., in the week prior to the start of the DTMS treatment) and at week 5 (i.e., in the week following the end of the DTMS treatment). Primary outcome measures were rates of response and remission at week 5 using an intention-to-treat approach. Results. Response and remission rates at week 5 were 70.6 and 41.2%, respectively. Also, depression, anxiety, and suicidality ratings were significantly improved by week 5 (with Hedges’ g estimates ranging from 0.6 to 1.72), as well as four of the five QOL domain scores (i.e., global, psychological, environmental and social). Finally, two patients dropped out of the study at week 1 because of significant scalp discomfort during stimulation. Conclusions. Our study suggests that DTMS, when used as an augmenting strategy for antidepressants in severe TRD, is efficacious, safe and relatively well tolerated. However, controlled studies with larger samples are needed to confirm and expand our preliminary findings.