***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: Background Repetitive Transcranial Magnetic Stimulation ( rTMS ) is an effective treatment for Major Depressive Disorder ( MDD ) , and is based upon delivery of focal high-energy pulses of electromagnetic stimulation . We postulated that delivery of rTMS at the subject ’s individual alpha frequency ( synchronized TMS , or sTMS ) would achieve efficacy with lower energy of stimulation . We developed a device that rotates neodymium cylindrical magnets at three locations along the midline above the subject ’s scalp to impart low-energy , sinusoidal-waveform magnetic brain stimulation over a broad area , and performed this efficacy study . Method Fifty-two subjects with MDD were enrolled in a r and omized , sham controlled , double-blind treatment study ( Trial Registration : NCT01683019 ) . Forty-six subjects were included in the final analysis . Most subjects received concurrent antidepressant medications that remained unchanged during the study . Subjects were r and omized to three treatment groups : 1 ) active sTMS with a fixed frequency at the subject ’s alpha frequency ; 2 ) active sTMS with a r and om stimulus frequency that varied between 8 Hz and 13 Hz ; and , 3 ) sham sTMS . 20 half-hour sTMS sessions were administered 5 days per week for 4 weeks . Results Subjects with either fixed or r and om frequency active sTMS had statistically significantly greater percentage reduction in depression severity compared to sham ( 48.5 % vs. 19.3 % , respectively ; p = 0.001 ) . No significant difference was found between fixed and r and om groups ( p = 0.30 ) . No significant side effects were reported . Conclusions These results suggest that sTMS may be an effective treatment for MDD BACKGROUND Theta-burst transcranial magnetic stimulation ( TBS ) has been shown to induce potent and long lasting effects on cortical excitability . In a previous open study , we demonstrated safety , tolerability and antidepressant properties of continuous TBS ( cTBS ) in major depression ( MD ) . The present study was aim ed to evaluate the therapeutic efficacy of cTBS in depressed patients using a double-blind , sham-controlled design . METHODS Twenty nine patients with MD were r and omized to receive either active cTBS to the right dorsolateral prefrontal cortex ( n=15 ) or sham cTBS ( n=14 ) for 10 consecutive work days . After the 10th session , patients who received sham TBS were crossed over to active cTBS which consisted of 10 daily sessions . Patients who received active cTBS continued with the same treatment protocol for additional 10 treatments . Each treatment session consisted of 3600 stimuli at an intensity of 100 % of the active motor threshold . Severity of depression was assessed weekly . RESULTS Overall , there was no significant difference in the degree of clinical improvement between active and sham cTBS groups . However , in patients whose medication status remained unchanged before the trial ( n=8 ) and in those who were medication-free ( n=3 ) , active cTBS result ed in a significantly greater reduction of Hamilton depression scores as compared to sham cTBS . LIMITATIONS A small sample size , confounding effect of medication and short treatment period . CONCLUSIONS Our results suggest that the antidepressant effect of cTBS is modest , yet it might be beneficial to patients nonresponsive to ongoing pharmacological treatment . A direct comparison between cTBS and conventional rTMS protocol s is warranted Objectives : Transcranial direct current stimulation ( tDCS ) has demonstrated some efficacy in treatment-resistant major depression ( TRD ) . The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex ( DLPFC ) and a control location such as the supraorbital region for the cathode . Several open-label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC . Thus , this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS . Methods : Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital . Twenty-four subjects with TRD and a 17-item Hamilton Rating Scale for Depression greater than 21 were r and omized to receive tDCS or sham tDCS . The rates of remission were compared between the two treatment groups . Results : The remission rates did not differ significantly between the two groups using an intention to treat analysis . More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode . Side effects did not differ between the two groups and in general the treatment was very well tolerated . Conclusion : Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD . However , a number of method ological limitations warrant caution in generalizing from this study . Ongoing , controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD . Clinical Trials.gov Identifier : NCT01078948 Although accelerated repetitive Transcranial Magnetic Stimulation ( rTMS ) paradigms and intermittent Theta-burst Stimulation ( iTBS ) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression ( TRD ) , accelerated iTBS treatment has not yet been studied . In this registered r and omized double-blind sham-controlled crossover study , spread over four successive days , 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex ( DLPFC ) . The accelerated iTBS treatment procedure was found to be safe and result ed in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation ( real/sham ) . While only 28 % of the patients showed a 50 % reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure , this response rate increased to 38 % when assessed two weeks after the end of the sham-controlled iTBS protocol , indicating delayed clinical effects . Importantly , 30 % of the responders were considered in clinical remission . We found no demographic predictors for response . Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND 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 . METHOD 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 . RESULTS Subjects were moderately treatment resistant .  Active treatment result ed 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 . CONCLUSIONS rTMS given twice daily was effective and safe , with no adverse neuropsychological effects BACKGROUND We tested whether transcranial magnetic stimulation ( TMS ) over the left dorsolateral prefrontal cortex ( DLPFC ) is effective and safe in the acute treatment of major depression . METHODS In a double-blind , multisite study , 301 medication-free patients with major depression who had not benefited from prior treatment were r and omized to active  ( n = 155 ) or  sham TMS  ( n = 146 ) conditions . Sessions were conducted five times per week with TMS at 10 pulses/sec , 120 % of motor threshold , 3000 pulses/session , for 4 - 6 weeks . Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale ( HAMD ) and response and remission rates with the MADRS and HAMD . RESULTS Active TMS was significantly superior to sham TMS on the MADRS at week 4 ( with a post hoc correction for ine quality in symptom severity between groups at baseline ) , as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6 . Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6 . Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales ( but not the HAMD17 scale ) . Active TMS was well tolerated with a low dropout rate for adverse events ( 4.5 % ) that were generally mild and limited to transient scalp discomfort or pain . CONCLUSIONS Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported . It offers clinicians a novel alternative for the treatment of this disorder In previous studies , fast repetitive transcranial magnetic stimulation ( rTMS ) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS . However , it is not clear whether fast rTMS is superior to slow rTMS ( frequency < or = 1 Hz ) which is safe at therapeutically promising higher intensities . The aim of this double-blind study was to compare the action of fast , slow and sham rTMS .  Eighteen patients with pharmacotherapy-resistant major depression were r and omized to receive fast ( 10 Hz ) , slow ( 0.3 Hz ) or sham rTMS with 250 stimuli/day for 5 successive days . rTMS was applied at 90 % motor threshold intensity to the left dorsolateral prefrontal cortex . Scores on the Hamilton Depression Rating Scale ( HDRS ) , but not on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , showed a statistically significant time x group interaction with a reduction of 19 % after slow rTMS . However , the effect was clinical ly marginal and not reflected by self-rating scores . Verbal memory and reaction performance were not impaired after rTMS , and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS . In conclusion , this study further supported the safety of rTMS but does not show any clinical ly meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 OBJECTIVE High-frequency left-side repetitive transcranial magnetic stimulation ( rTMS ) and low-frequency stimulation to the right prefrontal cortex have both been shown to have antidepressant effects , but doubts remain about the magnitude of previously demonstrated treatment effects . The authors evaluated sequentially combined high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex for treatment-resistant depression . METHOD The authors conducted a 6-week double-blind , r and omized , sham-controlled trial in 50 patients with treatment-resistant depression .  Three trains of low-frequency rTMS to the right prefrontal cortex of 140 seconds ' duration at 1 Hz were applied daily , followed immediately by 15 trains of 5 seconds ' duration of high-frequency left-side rTMS at 10 Hz . Sham stimulation was applied with the coil angled at 45 degrees from the scalp , resting on the side of one wing of the coil . The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale . RESULTS There was a significantly greater response to active than sham stimulation at 2 weeks and across the full duration of the study . A significant proportion of the study group receiving active treatment met response ( 11 of 25 [ 44 % ] ) or remission ( nine of 25 [ 36 % ] ) criteria by study end compared to the sham stimulation group ( two of 25 [ 8 % ] and none of 25 respectively ) . CONCLUSIONS Sequentially applying both high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex , has substantial treatment efficacy in patients 
    Output:
    
Several non‐invasive brain stimulation treatments seem efficacious across different outcome metrics .
All‐cause discontinuation rates indicate no differences between sham and active treatment .
There were no differences in all‐cause discontinuation rates .
The strongest evidence was for high‐frequency rTMS over the left DLPFC .
Intermittent TBS provides an advance in terms of reduced treatment duration .
tDCS is a potential treatment for non‐treatment resistant depression .
To date , there is not sufficient published data available to draw firm conclusions about the efficacy and acceptability of TBS and sTMS