***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: 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 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 The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy . We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram . However , because a recent meta- analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients , we decided to make an interim analysis . METHOD In patients with medication-resistant major depression we administered in a r and omised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily . After the last rTMS , the patients were followed for another 9 weeks on 20 mg escitalopram daily . The antidepressant effect was measured by the HAM-D(6 ) as primary outcome scale . RESULTS A total of 45 patients with complete data were r and omised so that 23 patients received sham TMS and 22 patients received active , high-frequency rTMS over the left cortex . Over the 3 weeks , the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6 ) above 0.70 , which indicates not only a statistically but also a clinical ly significant effect . The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study . Both the rTMS and escitalopram were well-tolerated . CONCLUSION High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants BACKGROUND Treatment-resistant depression ( TRD ) is a long-term , disabling illness . We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with st and ard care . METHOD This 2-year prospect i ve , multicenter , observational study ( patients enrolled from January 2001 through July 2004 ) tracked the outcomes of 124 patients with treatment-resistant , nonpsychotic major depressive disorder ( N = 109 ) or bipolar depressed phase disorder ( N = 15 ) who received treatment as usual ( TAU ) ( i.e. ,  any therapeutic regimen agreed to by patients and psychiatrists , including medications , electroconvulsive therapy [ ECT ] , and psychotherapy ) . Treatments could be adjusted , started , and stopped as necessary . The primary outcome , treatment response , was defined a priori as > or = 50 % improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS-SR-30 ) . Remission was defined as an IDS-SR-30 score of < or = 14 . The Medical Outcomes Study ( MOS ) 36-item Short Form Health Survey ( SF-36 ) was used to monitor quality -of-life changes . RESULTS The 12- and 24-month IDS-SR-30 response rates were 11.6 % ( 13/112 ) and 18.4 % ( 19/103 ) , respectively . Of the 13 responders at 12 months , only 5 were responders at 24 months . The 12- and 24-month IDS-SR-30 remission rates were 3.6 % ( 4/112 ) and 7.8 % ( 8/103 ) , respectively . Only 1 of the 4 12-month remitters was also a remitter at 24 months . The SF-36 indicated globally poor quality of life in this sample . CONCLUSIONS Despite the wide range of treatment options available for depression , the response rates , remission rates , and quality -of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU Rapid transcranial magnetic stimulation ( rTMS ) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects . Older depressed patients , however , in one study showed a lower response rate than younger patients . The current study examined treatment response in 20 depressed , treatment-refractory patients ( mean age 60.7 + /- 9.8 years ) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80 % of motor threshold or identical placebo stimulation , after patients had been withdrawn from their antidepressants . There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days ' follow-up . There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders ( p = .03 ) . These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS 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 Studies of repetitive transcranial magnetic stimulation ( rTMS ) in depression have found antidepressant effects when high frequency stimulation ( HF-rTMS ; > 1 Hz ) is applied over the left prefrontal cortex ( LPF ) . A few studies have also reported success with low frequency stimulation ( LF-rTMS ) to the right prefrontal cortex ( RPF ) . Both HF-rTMS and LF-rTMS have been reported to work better in areas with cerebral hypometabolism or hypermetabolism , respectively . Thirty medication-resistant patients with major depression were r and omized into three groups . The first group received sham rTMS and the second group received active rTMS ( 20-Hz rTMS to the LPF and 1-Hz rTMS to the RPF ) . The third group , however , received active rTMS that was focused on different regions of the brain after examination with single photon emission computed tomography ( 20-Hz rTMS to an area of relatively low activity and 1-Hz rTMS to an area showing relatively high activation ) . Patients and raters were blind to the treatment condition . Comparison of the sham rTMS group with the overall group that received active rTMS revealed statistically significant changes on the Hamilton Rating Scale for Depression after 10 sessions . This study demonstrated that combined 20 + 1-Hz rTMS was effective , but no additional advantages were obtained by focusing rTMS on areas identified by single photon emission tomography as showing high versus low levels of functional activity 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 OBJECTIVE The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation ( rTMS ) for treating resistant major depression were examined in a double-blind , controlled study . METHOD Eighteen medication-resistant depressed subjects were r and omly assigned to 2 weeks of real or sham rTMS , then permitted up to 4 weeks of real rTMS . Effects on mood , neuropsychological function , EEG , and hearing were assessed . RESULTS The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period , but there was no significant difference between groups . CONCLUSIONS Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment . A 4-week course of rTMS , as administered in this study , was safe In previous studies , fast repetitive transcranial magnetic stimulation ( rTMS ) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham 
    Output:
    
Conclusions : For patients with TRD , rTMS appears to provide significant benefits in short-term treatment studies .
However , the relatively low response and remission rates , the short duration s of treatment , and the relative lack of systematic follow-up studies suggest that further studies are needed before rTMS can be considered as a first-line monotherapy treatment for TRD