***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 Carefully design ed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation ( TMS ) in psychiatric disorders . A major method ological concern is the design of the " sham " control for TMS . An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment . Strategies employed so far include alterations in the position of the stimulating coil , but there has been little systematic study of their validity . In this study , we investigated the effects of different coil positions on cortical activation and scalp sensation . METHODS In nine normal subjects , single TMS pulses were administered at a range of intensities with a " figure eight " coil held in various positions over the left primary motor cortex . Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle . Scalp sensation to TMS  with the coil in various positions over the prefrontal area was also assessed . RESULTS None of the coil positions studied met the criteria for an ideal sham . Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex . CONCLUSIONS The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive " stimulation . " Further research is needed to develop the best sham condition for a range of applications 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 OBJECTIVE There is growing interest in neuropsychiatry for repetitive transcranial magnetic stimulation ( rTMS ) as a neuromodulatory treatment . However , there are limitations in interpreting rTMS effects as a real consequence of physiological brain changes or as placebo-mediated unspecific effects , which may be particularly strong in psychiatric patients . This is due to the fact that existing sham rTMS procedures are less than optimal . A new placebo tool is introduced here , called real electro-magnetic placebo ( REMP ) device , which can simulate the scalp sensation induced by the real TMS , while leaving both the visual impact and acoustic sensation of real TMS unaltered . METHODS Physical , neurophysiological and behavioural variables of monophasic and biphasic single-pulse TMS and biphasic 1Hz and 20Hz rTMS procedures ( at different intensities ) were tested in subjects who were expert or naïve of TMS . Results of the real TMS were compared with those induced by the REMP device and with two other currently used sham procedures , namely the commercially available Magstim sham coil and tilting the real coil by 90 degrees . RESULTS The REMP device , besides producing scalp sensations similar to the real TMS , attenuated the TMS-induced electric field ( as measured by a dipole probe ) to a biologically inactive level . Behaviourally , neither expert nor naïve TMS subjects identified the " coil at 90 degrees " or the " Magstim sham coil " as a real TMS intervention , whilst naïve subjects were significantly more likely to identify the REMP-attenuated TMS as real . CONCLUSIONS The " goodness of sham " of the REMP device is demonstrated by physical , neurophysiological , and behavioural results . SIGNIFICANCE Such placebo TMS is superior to the available sham procedures when applied on subjects naïve to TMS , as in case of patients undergoing a clinical rTMS trial 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 with treatment-resistant major depression . The treatment response accumulates to a clinical ly meaningful level over 4 to 6 weeks of active treatment BACKGROUND Repetitive transcranial magnetic stimulation ( TMS ) as a treatment for depression has shown statistically significant effects , but the clinical significance of these effects has been question ed . METHODS Patients with medication-resistant depression were r and omized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110 % the estimated prefrontal cortex threshold . Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains . The primary end point was treatment response defined as a > or=50 % decrease in Hamilton Depression Rating Scale ( HDRS ) score at both 1 and 2 weeks following the final repetitive TMS treatment . Remission was defined as a HDRS score < 8 . RESULTS The response rate for the TMS group was 30.6 % ( 11/35 ) , significantly ( p = .008 ) greater than the 6.1 % ( 2/33 ) rate in the sham group . The remission rate for the TMS group was 20 % ( 7/35 ) , significantly ( p = .033 ) greater than the 3 % ( 1/33 ) rate in the sham group . The HDRS scores showed a significantly ( p < .002 ) greater decrease over time in the TMS group compared with the sham group . CONCLUSIONS Transcranial magnetic stimulation can produce statistically and clinical ly significant antidepressant effects in patients with medication-resistant major depression CONTEXT Daily left prefrontal repetitive transcranial magnetic stimulation ( rTMS ) has been studied as a potential treatment for depression , but previous work had mixed outcomes and did not adequately mask sham conditions . OBJECTIVE To test whether daily left prefrontal rTMS safely and effectively treats  major depressive disorder . DESIGN Prospect i ve , multisite , r and omized , active sham-controlled ( 1:1 r and omization ) , duration -adaptive design with 3 weeks of daily weekday treatment ( fixed-dose phase ) followed by continued blinded treatment for up to another 3 weeks in improvers . SETTING Four US university hospital clinics . PATIENTS Approximately 860 out patients were screened , yielding 199 antidepressant drug-free patients with unipolar nonpsychotic major depressive disorder . INTERVENTION We delivered rTMS to the left prefrontal cortex at 120 % motor threshold ( 10 Hz , 4-second train duration , and 26-second intertrain interval ) for 37.5 minutes ( 3000 pulses per session ) using a figure-eight solid-core coil . Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations . MAIN OUTCOME MEASURE In the intention-to-treat sample ( n = 190 ) , remission rates were compared for the 2 treatment arms using logistic regression and controlling for site , treatment resistance , age , and duration of the current depressive episode . RESULTS Patients , treaters , and raters were effectively masked . Minimal adverse effects did not differ by treatment arm , with an 88 % retention rate ( 90 % sham and 86 % active ) . Primary efficacy analysis revealed a significant effect of treatment on the proportion of remitters ( 14.1 % active rTMS and 5.1 % sham ) ( P = .02 ) . The odds of attaining remission were 4.2 times greater with active rTMS than with sham ( 95 % confidence interval , 1.32 - 13.24 ) . The number needed to treat was 12 . Most remitters had low antidepressant treatment resistance . Almost 30 % of patients remitted in the open-label follow-up ( 30.2 % originally active and 29.6 % sham ) . CONCLUSION Daily left prefrontal rTMS as monotherapy produced statistically significant and clinical ly meaningful antidepressant therapeutic effects greater than sham . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00149838 Abstract Objectives . High frequency left-sided ( HFL ) and low frequency right-sided ( LFR ) unilateral repetitive transcranial magnetic stimulation ( rTMS ) are efficacious in treatment-resistant major depression ( TRD ) . Similar benefit has been suggested for sequential bilateral rTMS ( LFR then HFL ) . There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS . Therefore , this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD . Methods . Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital . Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale ( HDRS ) greater than 21 were r and omized to receive unilateral , bilateral , or sham rTMS . The rates of remission were compared among the three treatment groups . Results . The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy ( ECT ) during the current episode . The remission rate was significantly higher in the bilateral group than the sham group . The remission rate in the unilateral group did not differ from either group . Conclusion . These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD Selecting a suitable sham condition within the frame of repetitive transcranial magnetic stimulation ( rTMS ) treatment trials is a central issue . On the one h and , the ideal sham condition should not have a real stimulation effect ; on the other h and , it should not be recognized as sham by patients , particularly when considering that real stimulation conditions come along with rTMS specific side effects . Within the course of a multi-centre trial assessing the antidepressant effects of rTMS , patients were r and omized to sham or real stimulation , in both cases using a st and ard stimulation coil . In one centre , patients ( n=33 ) were asked about their impression whether they received the sham or the real treatment , and if they would recommend the treatment to others . 29 patients returned the question naires and were included into the analysis . From 15 subjects with real stimulation , 11 suggested to have obtained real , and 4 to have obtained sham . From 14 sham stimulated subjects , 9 suggested to have obtained the real condition and 5 to have been sham stimulated . This difference was not significant ( p=0.60 , chi square test ) . In addition , the major part of patients in both stimulation conditions would recommend rTMS  to others . In both conditions , real and sham , the majority of subjects believed to have obtained the real condition . This implies suitability of the sham condition used since subjects appeared not to be able to identify the condition . The results imply the feasibility of a valid sham condition with a " real " coil OBJECTIVES Repetitive transcranial magnetic stimulation ( rTMS ) has been shown to improve depressive symptoms . We design ed and carried out the following left prefrontal rTMS study to determine the safety , feasibility , and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder ( BPAD ) . METHODS We recruited and enrolled 23 depressed BPAD patients ( 12 BPI depressed state , nine BPII depressed state , two BPI mixed state ) . Patients were r and omly assigned to receive either daily left prefrontal rTMS ( 5 Hz , 1 
    Output:
    
In summary , existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation