***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of major depressive disorder ( MDD ) . PARTICIPANTS Participants included a group of 17 expert clinicians and research ers with expertise in the clinical application of rTMS , representing both the National Network of Depression Centers ( NNDC ) rTMS Task Group and the American Psychiatric Association Council on Research ( APA CoR ) Task Force on Novel Biomarkers and Treatments . EVIDENCE The consensus statement is based on a review of extensive literature from 2 data bases ( OvidSP MEDLINE and PsycINFO ) search ed from 1990 through 2016 . The search terms included variants of major depressive disorder and transcranial magnetic stimulation . The results were limited to articles written in English that focused on adult population s. Of the approximately 1,500 retrieved studies , a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice setting s. CONSENSUS PROCESS In cases in which the research evidence was equivocal or unclear , a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as " expert opinion . " CONCLUSIONS Multiple r and omized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy . These consensus recommendations , developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments , provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD Major depressive disorder ( MDD ) is a prevalent and disabling condition , and many patients do not respond to available treatments . Deep transcranial magnetic stimulation ( dTMS ) is a new technology allowing non-surgical stimulation of relatively deep brain areas . This is the first double-blind r and omized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD . We recruited 212 MDD out patients , aged 22 - 68 years , who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode . They were r and omly assigned to monotherapy with active or sham dTMS . Twenty sessions of dTMS ( 18 Hz over the prefrontal cortex ) were applied during 4 weeks acutely , and then biweekly for 12 weeks . Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale ( HDRS-21 ) score and response/remission rates at week 5 , respectively . dTMS induced a 6.39 point improvement in HDRS-21 scores , while a 3.28 point improvement was observed in the sham group ( p=0.008 ) , result ing in a 0.76 effect size . Response and remission rates were higher in the dTMS than in the sham group ( response : 38.4 vs. 21.4 % , p=0.013 ; remission : 32.6 vs. 14.6 % , p=0.005 ) . These differences between active and sham treatment were stable during the 12-week maintenance phase . dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred . These results suggest that dTMS constitutes a novel intervention in MDD , which is efficacious and safe in patients not responding to antidepressant medications , and whose effect remains stable over 3 months of maintenance treatment Abstract 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 out patients 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 sample s are needed to confirm and exp and our preliminary findings BACKGROUND Electroconvulsive therapy ( ECT ) is an effective alternative for pharmacotherapy in treatment-resistant depressive patients , but the side effects limit its use . Transcranial magnetic stimulation ( TMS ) has been proposed as a refined alternative , but most studies do not indicate that TMS is as effective as ECT for severe depression . OBJECTIVE We propose that the limited effectiveness of st and ard TMS resides in its superficial effect on the cortex , although much of the pathophysiology of depression is associated with deeper and larger brain regions implicated in the reward system . Herein , we tested the effectiveness and safety of a novel TMS coil , the " H-coil , " which enables direct stimulation of deeper brain regions , at the expense of focality . METHODS We have studied the antidepressant and cognitive effects induced by 4 weeks of high-frequency ( 20 Hz ) repeated deep TMS ( DTMS ) over the prefrontal cortex ( PFC ) of 65 medication-free depressive patients , who have failed to benefit from prior medications . Patients were r and omly assigned to various treatment configurations , differing in stimulation intensity and laterality . Effects were assessed by the 24-item Hamilton depression rating scale ( HDRS-24 ) and several secondary outcome measures . RESULTS A significant improvement in HDRS scores was found when high , but not low , stimulation intensity was used . Several cognitive improvements were evident , and no treatment-related serious adverse events were observed . CONCLUSIONS DTMS over the PFC was found safe and effective in alleviating depression . The results accentuate the significance of deep , high-intensity stimulation over low , and serve as the first study to indicate the potential of DTMS in psychiatric and neurologic disorders OBJECTIVES Deep transcranial magnetic stimulation ( DTMS ) is an emerging and promising treatment for major depression . In our study , we explored the effectiveness of a second antidepressant course of deep TMS in major depression . We enrolled eight patients who had previously responded well to DTMS but relapsed within 1 year in order to evaluate whether a second course of DTMS would still be effective . METHODS Eight depressive patients who relapsed after a previous successful deep TMS course expressed their wish to be treated again . Upon their request , they were recruited and treated with 20 daily sessions of DTMS at 20 Hz using the Brainsway 's H1 coil . The Hamilton depression rating scale ( HDRS ) , Hamilton anxiety rating scale ( HARS ) and the Beck depression inventory ( BDI ) were used weekly to evaluate the response to treatment . RESULTS Similar to the results obtained in the first course of treatment , the second course of treatment ( after relapse ) induced significant reductions in HDRS , HARS and BDI scores , compared to the ratings measured prior to treatment . The magnitude of response in the second course was smaller relative to that obtained in the first course of treatment . CONCLUSIONS Our results suggest that depressive patients who previously responded well to deep TMS treatment are likely to respond again . However , the slight reduction in the magnitude of the response in the second treatment raises the question of whether tolerance or resistance to this treatment may eventually develop Late-life  depression ( LLD ) is a growing worldwide problem due to demographic changes , with limited treatment options due to high rates of pharmacotherapy adverse effects , accessibility of psychotherapy , and tolerability of electroconvulsive therapy . Novel neuromodulation techniques , such as repetitive transcranial magnetic stimulation ( rTMS ) , may overcome these limitations . The objective of this study is to determine the efficacy , tolerability , and cognitive effects of high-dose deep rTMS in LLD . In this study we r and omized older adults between 60 and 85 years old with major depressive disorder ( MDD ) to sham or active deep rTMS ( H1 coil , 6012 pulses , 18 Hz , 120 % of resting motor threshold ) delivered over the dorsolateral and ventrolateral prefrontal cortex 5 days per week over 4 weeks . Our primary outcome was remission of depression in an intention-to-treat analysis . We also assessed change in cognitive functioning with rTMS treatment and tolerability based on adverse effects . Fifty-two participants were r and omized to active ( n = 25 ) or sham H1 coil ( n = 27 ) . Remission rate was significantly higher with active than sham rTMS ( 40.0 % vs 14.8 % ) with a number needed to treat of 4.0 ( 95 % CI : 2.1–56.5 ) . There was no change on any measure of executive function and no serious adverse events . Adverse effect profiles were similar between active and sham rTMS , except for reports of pain being significantly more common in the active condition ( 16.0 % vs 0 % ) . High-dose deep rTMS appears to be safe , well tolerated , and efficacious in the treatment of LLD INTRODUCTION Chronic treatment resistant depression takes a substantial toll on patients ' quality of life and alternative treatment options are limited . This prospect i ve multicenter study evaluated the safety , tolerability and efficacy of four weeks of thrice-a-week deep transcranial magnetic stimulation ( dTMS ) in combination with selective serotonin reuptake inhibitors ( SSRIs ) . METHODS Forty patients who failed to respond during a 16-week double-blind placebo controlled ( DBPC ) trial of dTMS or sham dTMS as monotherapy were screened and started a treatment of previously tolerable but ineffective SSRI . After ten days of medication , high frequency dTMS was added three times a week for four weeks . RESULTS dTMS combined with SSRIs was well tolerated , with only headaches as a related adverse event ( n = 4 ) , which did not cause drop outs . Six patients were excluded from analysis : 1 was missing screening data and 5 received less than 10 sessions . Out of 34 patients included in this study , 12 ( 35.3 % ) patients remitted ( HDRS-21 < 10 ) . No significant differences were found between patients who had received sham or active dTMS in the earlier DBPC multicenter trial . LIMITATIONS This was a small scale open study of dTMS with SSRIs in patients that failed to respond during a DBPC dTMS trial , although a carryover effect can not be excluded . Comparative efficacy of dTMS with and without SSRIs and specific dosing and protocol parameters warrant specifically- design ed large-scale controlled studies . CONCLUSIONS Thrice weekly dTMS at 120 % motor threshold(MT ) , 10 HZ , 3‑s trains , 20‑s intervals , 2400 daily pulses , can augment formerly ineffective SSRI treatment OBJECTIVE 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 . METHODS This was a secondary analysis of a r and omized noninferiority trial ( N=388 ) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation ( iTBS ) rTMS .  Participants were adult out patients 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 . RESULTS 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 . CONCLUSIONS 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 protocol Repetitive transcranial magnetic stimulation ( rTMS ) is 
    Output:
    
Importantly , the dTMS group showed favorable tolerability without major adverse events .
CONCLUSIONS dTMS is a safe and effective intervention in patients with TRD .
Studies combining dTMS and antidepressant medications seemed to show greater therapeutic effects .