Repetitive Transcranial Magnetic Stimulation for People With Treatment-Resistant Depression: A Health Technology Assessment.
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SUBMITTER: Ontario Health (Quality)
PROVIDER: S-EPMC8129638 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Repetitive Transcranial Magnetic Stimulation for People With Treatment-Resistant Depression: A Health Technology Assessment.
Ontario health technology assessment series 20210506 4
<h4>Background</h4>Major depression is one of the most diagnosed mental illnesses in Canada. Generally, people are treated successfully with antidepressants or psychotherapy, but some people do not respond to these treatments (called treatment-resistant depression [TRD]). Repetitive transcranial magnetic stimulation (rTMS) delivers magnetic pulses to stimulate the areas of the brain associated with mood regulation. Several modalities of rTMS exist (e.g., high frequency rTMS, intermittent theta b ...[more]
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Project description:Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD. Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13-21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a >50% reduction in Ham-D scores. Safety and tolerability were also examined. Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p < 0.00001). We observed 18 (56%) responders (? 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ? 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%. Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01731678.
| S-EPMC6449763 | biostudies-literature
Project description:BACKGROUND:The management of late-life depression is challenged by high rates of treatment-resistance and adverse effects, along with medical comorbidities and polypharmacy. Together with the limited data on managing treatment-resistant depression in older adults, there is a need for investigating the efficacy of nonpharmacological treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is one modality that may better serve this patient population. METHODS:The present study examines data from two previous clinical trials (NCT00305045 and NCT01515215) to explore the efficacy of bilateral and unilateral high-frequency left-sided (HFL) rTMS in older adults suffering from treatment-resistant depression. A total of 43 adults aged 60 or older with a current major depressive episode were randomized to bilateral sequential, unilateral HFL, or sham. Bilateral sequential stimulation involved low-frequency (1 Hz) right dorsolateral prefrontal cortex (DLPFC) stimulation followed immediately by high-frequency (10 Hz) left DLPFC. The unilateral condition was HFL stimulation alone, and the placebo condition was either HFL or sequential bilateral form of sham. The primary outcome was remission of depression. RESULTS:Participants receiving bilateral rTMS experienced greater remission rates (40%) compared with unilateral (0%) or sham (0%) groups. Response to rTMS in the Hamilton Depression Rating Scale scores similarly favored the efficacy of bilateral rTMS. CONCLUSION:This study suggests that sequential bilateral treatment may be an optimal form of rTMS when used for treatment-resistant depression in older adults. Further large-scale comparative effectiveness trials of bilateral rTMS in this population are warranted.
| S-EPMC6488425 | biostudies-literature
Project description:BackgroundA significant proportion of patients with major depressive disorder (MDD) failed to respond to antidepressant medications. Repetitive transcranial magnetic stimulation (rTMS) is an effective option for treating such treatment-resistant patients with MDD (TRD). Reliable clinical predictors for antidepressant responses to rTMS remain elusive.MethodsIn total, 212 patients with MDD who failed to respond to at least one adequate antidepressant trial and had a detailed evaluation before rTMS were recruited for chart review. Demographic data, clinical characteristics, psychiatric comorbidities, symptom ratings [e.g., objective and subjective depression, life stress, depression refractoriness by Maudsley Staging Method (MSM)], and antidepressant treatment responses were analyzed.ResultsMSM-subitem1 (duration of current depressive episode; Beta = 0.209, p = 0.004), MSM-subitem5 (a history of ECT treatment; Beta = -0.210, p = 0.004), and psychiatric admissions (Beta = 0.241, p = 0.001) predicted antidepressant response of rTMS treatment. ECT was underutilized (only 3.3%). Psychiatric admissions [Exp(B) = 1.382, p = 0.021], a comorbidity of OCD [0.047, 0.005], and life stress level [0.984, 0.029] predicted the history of ECT treatment.ConclusionSeveral clinical variables (e.g., number of psychiatric admissions, OCD as a comorbidity, and life stress level) were reliable clinical factors associated with antidepressant responses of rTMS treatment and may be utilized in combination with MSM subitems to evaluate levels of TRD.
| S-EPMC9757691 | biostudies-literature
Project description:Repetitive transcranial magnetic stimulation (rTMS) has become a useful tool to treat different neuropsychiatric conditions such as depression, dementia and extrapyramidal syndromes insufficiently responding to conventional treatment. In this SHAM-controlled exploratory study safety, symptom improvement as well as changes in inflammation markers and neurotransmitter precursor amino acids availability were studied after a prefrontal cortex (PFC) stimulation using rTMS as add-on treatment in 29 patients with geriatric depression. Out of these, ten patients received SHAM treatment. Treatment was well tolerated, no serious adverse effects were observed. A clear improvement in symptoms of depression with a significant decrease in the HAMD-7 (U = 3.306, p = 0.001) was found by rTMS treatment. In parallel, serum phenylalanine dropped significantly (U = 2.340, p < 0.02), and there was a decline of tryptophan and of Phe/Tyr concentrations, both the effects, however, failed to reach the levels of statistical significance. In the patients who underwent SHAM treatment, no significant changes of HAMD-7 or the concentrations of any biomarker in the study could be found. In addition to the significant effect of rTMS on depression scores, these results point to a possible influence of rTMS on the enzyme phenylalanine hydroxylase (PAH), which plays a crucial role in the biosynthesis of neurotransmitter precursors related to geriatric depression.
| S-EPMC6647391 | biostudies-literature
Project description:ObjectivesTo evaluate the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT), and combining both treatments in a stepped care pathway for patients with treatment-resistant depression (TRD) in Ontario.MethodsA cost-utility analysis evaluated the lifetime costs and benefits to society of rTMS and ECT as first-line treatments for TRD using a Markov model, which simulates the costs and health benefits of patients over their lifetime. Health states included acute treatment, maintenance treatment, remission, and severe depression. Treatment efficacy and health utility data were extracted and synthesized from randomized controlled trials and meta-analyses evaluating these techniques. Direct costing data were obtained from national and provincial costing databases. Indirect costs were derived from government records. Scenario, threshold, and probabilistic sensitivity analyses were performed to test robustness of the results.ResultsrTMS dominated ECT, as it was less costly and produced better health outcomes, measured in quality-adjusted life years (QALYs), in the base case scenario. rTMS patients gained an average of 0.96 additional QALYs (equivalent to approximately 1 year in perfect health) over their lifetime with costs that were $46,094 less than ECT. rTMS remained dominant in the majority of scenario and threshold analyses. However, results from scenarios in which the model's maximum lifetime allowance of rTMS treatment courses was substantially limited, the dominance of rTMS over ECT was attenuated. The scenario that showed the highest QALY gain (1.19) and the greatest cost-savings ($46,614) was when rTMS nonresponders switched to ECT.ConclusionFrom a societal perspective utilizing a lifetime horizon, rTMS is a cost-effective first-line treatment option for TRD relative to ECT, as it is less expensive and produces better health outcomes. The reduced side effect profile and greater patient acceptability of rTMS that allow it to be administered more times than ECT in a patient's lifetime may contribute to its cost-effectiveness.
| S-EPMC7019468 | biostudies-literature
Project description:Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for depression; however, its potential has likely been hindered due to non-optimized targeting, unclear ideal stimulation parameters, and lack of information regarding how the brain is physiologically responding during and after stimulation. While neuroimaging is ideal for obtaining such critical information, existing modalities have been limited due to poor resolutions, along with significant noise interference from the electromagnetic spectrum. In this study, we used a novel diffuse optical tomography (DOT) device in order to advance our understanding of the neurophysiological effects of rTMS in depression. Healthy and depressed subjects aged 18-70 were recruited. Treatment parameters were standardized with targeting of the left dorsolateral prefrontal cortex with a magnetic field intensity of 100% of motor threshold, pulse frequency of 10 per second, a 4 s stimulation time and a 26 s rest time. DOT imaging was simultaneously acquired from the contralateral dorsolateral prefrontal cortex. Six healthy and seven depressed subjects were included for final analysis. Hemoglobin changes and volumetric three-dimensional activation patterns were successfully captured. Depressed subjects were observed to have a delayed and less robust response to rTMS with a decreased volume of activation compared to healthy subjects. In this first-in-human study, we demonstrated the ability of DOT to safely and reliably capture and compare cortical response patterns to rTMS in depressed and healthy subjects. We introduced this emerging optical functional imaging modality as a novel approach to investigating targeting, new treatment parameters, and physiological effects of rTMS in depression.
| S-EPMC8016845 | biostudies-literature
Project description:BackgroundPeripartum depression is a common disorder with very high potential hazards for both the patients and their babies. The typical treatment options include antidepressants and electroconvulsive therapy. However, these treatments do not ensure the safety of the fetus. Recently, repetitive transcranial magnetic stimulation has emerged as a promising treatment for neuropathies as well as depression. Nevertheless, many studies excluded pregnant women. This systematic review was conducted to confirm whether repetitive transcranial magnetic stimulation was a suitable treatment option for peripartum depression.MethodsWe performed a systematic review that followed the PRISMA guidelines. We searched for studies in the MEDLINE, PsycINFO, EMBASE, and Cochrane library databases published until the end of September 2020. Eleven studies were selected for the systematic review, and five studies were selected for quantitative synthesis. Data analysis was conducted using Comprehensive Meta-Analysis 3 software. The effect size was analyzed using the standardized mean difference, and the 95% confidence interval (CI) was determined by the generic inverse variance estimation method.ResultsThe therapeutic effect size of repetitive transcranial magnetic stimulation for peripartum depression was 1.394 (95% CI: 0.944-1.843), and the sensitivity analysis effect size was 1.074 (95% CI: 0.689-1.459), indicating a significant effect. The side effect size of repetitive transcranial magnetic stimulation for peripartum depression was 0.346 (95% CI: 0.214-0.506), a meaningful result. There were no severe side effects to the mothers or fetuses.ConclusionsFrom various perspectives, repetitive transcranial magnetic stimulation can be considered an alternative treatment to treat peripartum depression to avoid exposure of fetuses to drugs and the severe side effects of electroconvulsive therapy. Further research is required to increase confidence in the results.
| S-EPMC7874443 | biostudies-literature
Project description:ObjectivesThe authors previously reported that repetitive transcranial magnetic stimulation (rTMS) produced a response rate of 39.4% among 62 patients with treatment resistant vascular depression. This study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS.DesignPatients were randomly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods. After rTMS, all patients were given 20 mg/day of citalopram for 9 weeks and reevaluated at 3, 6, and 9 weeks.SettingOutpatient continuation treatment trial.ParticipantsPatients with vascular depression (N = 62), as determined by magnetic resonance imaging hyperintensities and three or more clinical risk factors for vascular disease without other major medical illness, were recruited. They had onset of major depression after age 50 and failed at least one trial of antidepressants.InterventionAfter rTMS or sham treatment, all treatment responders were given citalopram for 9 weeks.ResultsAmong the 33 patients who were given rTMS, 13 responded (i.e., >50% decline in Hamilton Depression Scale score). Of these 13, all completed the 9 weeks of continuation treatment. There were nine patients who continued to be responders and four who had a relapse of depression.ConclusionMore effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders.
| S-EPMC2758492 | biostudies-literature
Project description:BackgroundRepetitive 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.MethodsData 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.FindingsIn 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.InterpretationThere 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.FundingCanadian Institutes of Health Research, Brain Canada.
| S-EPMC9722479 | biostudies-literature
Project description:ImportanceTreatment-resistant major depression (TRMD) in veterans is a major clinical challenge given the high risk for suicidality in these patients. Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a novel treatment modality for these veterans.ObjectiveTo determine the efficacy of rTMS in the treatment of TRMD in veterans.Design, setting, and participantsA double-blind, sham-controlled randomized clinical trial was conducted from September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A total of 164 veterans with TRD participated.InterventionsParticipants were randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold, 4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment sessions.Main outcomes and measuresThe primary dependent measure of the intention-to-treat analysis was remission rate (Hamilton Rating Scale for Depression score ≤10, indicating that depression is in remission and not a clinically significant burden), and secondary analyses were conducted on other indices of posttraumatic stress disorder, depression, hopelessness, suicidality, and quality of life.ResultsThe 164 participants had a mean (SD) age of 55.2 (12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these, 81 were randomized to receive active rTMS and 83 to receive sham. For the primary analysis of remission, there was no significant effect of treatment (odds ratio, 1.16; 95% CI, 0.59-2.26; P = .67). At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active treatment group achieved remission of depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment group. Overall, 64 of 164 (39.0%) of the participants achieved remission.Conclusions and relevanceA total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population.Trial registrationClinicalTrials.gov Identifier: NCT01191333.
| S-EPMC6142912 | biostudies-literature