***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 Current efforts to improve clinical effectiveness and utility of repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of major depression ( MD ) include theta burst stimulation ( TBS ) , a patterned form of rTMS . Here , we investigated the efficacy of bilateral TBS to the dorsolateral prefrontal cortex ( dlPFC ) in patients with MD in additon to ongoing medication and psychotherapy . METHODS In this r and omized-controlled trial , thirty-two patients with MD were treated for six weeks ( thirty sessions ) with either successively intermittent , activity enhancing TBS ( iTBS ) to the left and continuous , inhibiting TBS ( cTBS ) to the right dlPFC or with bilateral sham stimulation . Primary outcome measure was the proportion of treatment response defined as a Montgomery-Åsberg Depression Rating Scale (MADRS)≤50 % compared to baseline . Secondary outcomes comprised response and remission rates of the Hamilton Depression Rating Scale ( HAMD ) and the Beck Depression Inventory ( BDI ) . RESULTS A larger number of responders were found in the cTBS ( n=9 ) compared to the sham-stimulation ( n=4 ) group ( odds ratio : 3.86 ; Wald χ(2)=3.9 , p=0.048 ) . On secondary endpoint analysis , patient-reported outcome as assessed by the BDI , pointed towards a higher rate of remitters in the cTBS ( n=6 ) than in the sham ( n=1 ) group ( odds ratio : 9 ; Wald χ(2)=3.5 , p=0.061 ) . LIMITATIONS With regard to the pilot character of the study and the small sample size , the results have to be considered as preliminary . CONCLUSIONS These findings provide first evidence that six weeks treatment of MDD with iTBS to the left and cTBS to the right dlPFC for six weeks is safe , feasible and superior to sham stimulation applied add-on to pharmacological and psychotherapeutic treatment 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 This 5-week , r and omized , double-blind , placebo-controlled trial investigated the efficacy and tolerability of high frequency repetitive transcranial magnetic stimulation ( rTMS ) directed to the left prefrontal cortex in drug-resistant depressed patients . Fifty-four patients were r and omly assigned to receive 10 daily applications of either real or sham rTMS . Subjects assigned to receive active stimulation were divided into two further subgroups according to the intensity of stimulation : 80 % vs. 100 % of motor threshold ( MT ) . At study completion , the response rates were 61.1 % ( n=11 ) , 27.8 % ( n=5 ) and 6.2 % ( n=1 ) for the 100 % MT group , 80 % MT group and sham group , respectively . A significant difference ( Pearson chi(2 ) test ) was found between the 100 % MT and sham groups , while the 80 % MT group did not differ significantly from the sham group . Between the two active groups , a marginally significant difference was observed . Analysis of variance with repeated measures on Hamilton Depression Rating Scale scores revealed a significantly different decrease over time of depressive symptomatology among the three treatment groups . Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded , and on the whole the technique was well tolerated . The results of this double-blind trial showed that rTMS may be a useful and safe adjunctive treatment for drug-resistant depressed patients BACKGROUND Major depression is a worldwide severe mental health problem . Unfortunately , not all depressed patients respond to pharmacotherapy or psychotherapy , even when adhering to treatment guidelines . Even though current guidelines do not in particular advocate repetitive Transcranial Magnetic Stimulation ( rTMS ) in refractory treatment resistant depression ( TRD ) , using more intensive stimulation parameters might hold promise as a valuable alternative . OBJECTIVE Consequently , in this r and omized sham-controlled crossover study , we wanted to evaluate clinical outcome of intensive HF-rTMS treatment in TRD when applied to the left dorsolateral prefrontal cortex ( DLPFC ) . METHODS After a 2-week antidepressant washout , 20 unipolar TRD patients , at least stage III , received 20 sham-controlled high-frequency (HF)-rTMS sessions , in a crossover design . Five daily suprathreshold HF-rTMS sessions were spread over four successive days delivering in total 31,200 stimuli . RESULTS Overall , the procedure result ed in immediate statistical significant decreases in depressive symptoms regardless of order/type of stimulation ( real/sham ) , suggesting possible placebo responses . On the other h and , albeit only 35 % ( 7/20 ) of the patients showed a 50 % reduction of their initial Hamilton Depression rating score at the end of the two-week procedure , all these patients showed a prompt clinical response after real HF-rTMS treatment , not after sham . Furthermore , a shorter duration of the current depressive episode was a predictor for beneficial clinical outcome . Unresponsiveness to former ECT could be indicative for negative clinical outcome in these kinds of patients . LIMITATIONS Single center setup with relatively small sample size and no follow-up . CONCLUSIONS Our findings indicate that intensive HF-rTMS treatment might have the potential to result in fast clinical response when confronted with a refractory TRD patient BACKGROUND Multiple groups have reported on the use of repetitive transcranial magnetic stimulation ( rTMS ) in treatment-resistant major depression . The purpose of this study is to assess the efficacy of rTMS in unmedicated , treatment-resistant patients who meet criteria for major depression . METHODS Depressed subjects , who had failed to respond to a median of four treatment trials , were assigned in a r and omized double-blind manner to receive either active ( n = 10 ; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals ; delivered at 80 % motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex ) or sham ( n = 10 ; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp ) rTMS . These sequences were applied during 10 consecutive weekdays . Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained . RESULTS The group mean 25-item Hamilton Depression Rating Scale ( HDRS ) score was 37.2 ( + /- 2.0 SEM ) points . Adjusted mean decreases in HDRS scores were 14.0 ( + /- 3.7 ) and 0.2 ( + /- 4.1 ) points for the active and control groups , respectively ( p < .05 ) . One of 10 subjects receiving active treatment demonstrated a robust response ( i.e. , HDRS decreased from 47 to 7 points ) ; three other patients demonstrated 40 - 45 % decreases in HDRS scores . No patients receiving sham treatment demonstrated partial or full responses . CONCLUSIONS A 2-week course of active rTMS result ed in statistically significant but clinical ly modest reductions of depressive symptoms , as compared to sham rTMS in a population characterized by treatment resistance 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 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 BACKGROUND Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation ( rTMS ) over sham rTMS in patients with treatment-resistant depression ( TRD ) . These factors include unilateral stimulation ( i.e. , treatment of only the left dorsolateral prefrontal cortex [ DLPFC ] ) , suboptimal methods of targeting the DLPFC and insufficient stimulation intensity ( based on coil-to-cortex distance ) . METHODS We recruited patients with TRD between the ages of 18 and 85 years from a university hospital , and participants were r and omized to receive sequential bilateral rTMS ( 600 pulses at 1 Hz followed by 1500 pulses at 10 Hz ) , unilateral high-frequency left (HFL)-rTMS ( 2100 pulses at 10 Hz ) or sham rTMS for 3 or 6 weeks depending on treatment response . Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus , using 120 % of the coil-to-cortex adjusted motor threshold . Our primary outcome of interest was the remission rate . RESULTS A total of 121 patients participated in this study . The remission rate was significantly higher in the bilateral group than the sham group . The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups . There were no significant differences in reduction of depression scores among the 3 groups . LIMITATIONS The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials , and the sham condition did not involve active stimulation . CONCLUSION Our findings suggest 
    Output:
    
Placebo response was directly associated with publication year and depression improvement of the active group , and inversely associated with higher levels of treatment‐resistant depression .
Conclusion : Placebo response in rTMS depression trials was large and associated with depression improvement of the active treatment group .
Such result suggests that excluding placebo responders with a run‐in phase may not confer advantage since response to ‘ active ’ rTMS may decrease as well .
Moreover , placebo response may be a component of therapeutic response to rTMS in MDD .
Placebo response may be a component of the therapeutic response to rTMS depression trials