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      Repetitive Transcranial Magnetic Stimulation in Youth With Treatment Resistant Major Depression

      brief-report

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          Abstract

          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

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          Most cited references21

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          Diagnosis and definition of treatment-resistant depression.

          Treatment-resistant depression (TRD) typically refers to inadequate response to at least one antidepressant trial of adequate doses and duration. TRD is a relatively common occurrence in clinical practice, with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment. A diagnostic re-evaluation is essential to the proper management of these patients. In particular, the potential role of several contributing factors, such as medical and psychiatric comorbidity, needs to be taken into account. An accurate and systematic assessment of TRD is a challenge to both clinicians and researchers, with the use of clinician-rated or self-rated instruments being perhaps quite helpful. It is apparent that there may be varying degrees of treatment resistance. Some staging methods to assess levels of treatment resistance in depression are being developed, but need to be tested empirically. Copyright 2003 Society of Biological Psychiatry
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            Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis

            Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people.
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              Using the international 10-20 EEG system for positioning of transcranial magnetic stimulation.

              The International 10-20 system for EEG electrode placement is increasingly applied for the positioning of transcranial magnetic stimulation (TMS) in cognitive neuroscience and in psychiatric treatment studies. The crucial issue in TMS studies remains the reliable positioning of the coil above the skull for targeting a desired cortex region. In order to asses the precision of the 10-20 system for this purpose, we tested its projections onto the underlying cortex by using neuronavigation. In 21 subjects, the 10-20 positions F3, F4, T3, TP3, and P3, as determined by a 10-20 positioning cap, were targeted stereotactically. The corresponding individual anatomical sites were identified in the Talairach atlas. The main targeted regions were: for F3 Brodmann areas (BA) 8/9 within the dorsolateral prefrontal cortex, for T3 BA 22/42 on the superior temporal gyrus, for TP3 BA 40/39 in thearea of the supramarginal and angular gyrus, and for P3 BA 7/40 on the inferior parietal lobe. However, in about 10% of the measurements adjacent and possibly functionally distinct BAs were reached. The ranges were mainly below 20 mm. Using the 10-20 system for TMS positioning is applicable at low cost and may reach desired cortex regions reliably on a larger scale level. For finer grained positioning, possible interindividual differences, and therefore the application of neuroimaging based methods, are to be considered.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                29 March 2019
                2019
                : 10
                : 170
                Affiliations
                [1] 1Departments of Pediatrics and Psychiatry, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada
                [2] 2Strategic Clinical Network for Addictions and Mental Health, Alberta Health Services , Calgary, AB, Canada
                [3] 3Department of Psychiatry and Psychology, Mayo Clinic , Rochester, NY, United States
                [4] 4Institute of Mental Health Research, University of Ottawa , Ottawa, ON, Canada
                [5] 5Departments of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada
                Author notes

                Edited by: Noah S. Philip, Warren Alpert Medical School of Brown University, United States

                Reviewed by: Manreena Kaur, Monash University, Australia; Amin Zandvakili, Warren Alpert Medical School of Brown University, United States

                *Correspondence: Frank P. MacMaster fmacmast@ 123456ucalgary.ca

                This article was submitted to Neuroimaging and Stimulation, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2019.00170
                6449763
                30984044
                99669900-7d15-40af-94c1-56502f91655b
                Copyright © 2019 MacMaster, Croarkin, Wilkes, McLellan, Langevin, Jaworska, Swansburg, Jasaui, Zewdie, Ciechanski and Kirton.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 January 2019
                : 08 March 2019
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 29, Pages: 6, Words: 4142
                Funding
                Funded by: Alberta Children's Hospital Foundation 10.13039/501100003206
                Categories
                Psychiatry
                Brief Research Report

                Clinical Psychology & Psychiatry
                adolescent,depression,transcrancial magnetic stimulation (tms),dorsolateral prefrontal cortex (dlpfc),brain stimulation

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