***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 / OBJECTIVE Repetitive transcranial magnetic stimulation ( rTMS ) has been mainly studied as adjunctive treatment for drug-resistant patients . We assessed the effectiveness of rTMS started concomitantly with antidepressant medications in non-drug-resistant major depressive disorder patients . We also evaluated if , among the 3 antidepressants administered , one had a better synergy with rTMS . METHOD In this 5-week , double-blind , r and omized , sham-controlled study , we recruited 99 in patients suffering from a major depressive episode ( DSM-IV criteria ) . They were r and omly assigned to receive venlafaxine , sertraline , or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex . Data were gathered from February 2004 to June 2005 . RESULTS The active rTMS group showed a significantly faster reduction in Hamilton Rating Scale for Depression ( HAM-D ) scores compared with the sham group ( p = .0029 ) . The response and remission rates were significantly greater in the active rTMS group after the stimulation period ( p = .002 and p = .003 , respectively ) , but not at the endpoint . We found no significant difference in HAM-D score reduction among the 3 drugs administered , either in the active or in the sham group . CONCLUSION These findings support the efficacy of rTMS in hastening the response to antidepressant drugs in patients with major depressive disorder . The effect of rTMS seems to be unaffected by the specific concomitantly administered drug 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 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 OBJECTIVE The present study examined the efficacy and tolerability of acute escitalopram treatment in depressed patients aged 60 years or older . METHODS Patients aged > or = 60 years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition major depressive disorder were r and omized to 12 weeks of double-blind , flexible-dose treatment with escitalopram ( 10 - 20 mg/day ; N = 130 ) or placebo ( N = 134 ) . The prospect ively defined primary efficacy end point was change from baseline to week 12 in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score using the last observation carried forward approach . RESULTS A total of 109 ( 81 % ) patients in the placebo group and 96 ( 74 % ) patients in the escitalopram group completed treatment . Mean age in both groups was approximately 68 years . Mean baseline MADRS scores were 28.4 and 29.4 for the placebo and escitalopram treatment groups , respectively . Escitalopram did not achieve statistical significance compared with placebo in change from baseline on the MADRS ( least square mean difference : -1.34 ; last observation carried forward ) . Discontinuation rates result ing from adverse events were 6 % for placebo and 11 % for escitalopram . Treatment-emergent adverse events reported by > 10 % of patients in the escitalopram group were headache , nausea , diarrhea , and dry mouth . CONCLUSIONS Escitalopram treatment was not significantly different from placebo treatment on the primary efficacy measure , change from baseline to week 12 in MADRS . In patients aged 60 years or older with major depression , acute escitalopram treatment appeared to be well tolerated BACKGROUND Transcranial magnetic stimulation ( TMS ) is a noninvasive method to stimulate the cortex , and the treatment of depression is one of its potential therapeutic applications . Three recent meta analyses strongly suggest its benefits in the treatment of depression . The present study investigates whether repetitive TMS ( rTMS ) accelerates the onset of action and increases the therapeutic effects of amitriptyline . METHODS Forty-six out patients meeting DSM-IV criteria for nonpsychotic depressive episode were r and omly assigned to receive rTMS ( n = 22 ) or sham repetitive TMS ( sham ) ( n = 24 ) during 4 weeks over dorsolateral prefrontal cortex ( DLPFC ) in this double-blind controlled trial . All patients were concomitantly taking amitriptyline ( mean dose 110 mg/d ) . The rTMS group received 20 sessions ( 5 sections per week ) of 5 Hz rTMS ( 120 % of motor threshold and 1250 pulses per session ) . Sham stimulation followed the same schedule , however , using a sham coil . The efficacy variables were the Hamilton Depression Rating Scale-17 items ( HAM-D/17 ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , a Visual Analogue Scale ( VAS ) , and the Clinical Global Impression ( CGI ) . Tolerability was assessed by clinical examination and a safety screening of TMS side effects . RESULTS Repetitive TMS had a significantly faster response to amitriptyline . There was a significant decrease in HAM-D/17 scores , already after the first week of treatment ( p < .001 compared with baseline and p < .001 compared with sham ) . The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study ( p < .001 at fourth week ) . CONCLUSIONS Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline Objective : This study investigated the impact of latency ( the time between illness onset and initiation of prophylactic treatment ) on the outcome of prophylaxis in bipolar disorders Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day  ( n = 191 ) or placebo  ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated BACKGROUND / OBJECTIVE There is evidence for an antidepressant effect of repetitive transcranial magnetic stimulation ( rTMS ) , but little is known about posttreatment course . Therefore , we conducted a placebo-controlled , double-blind study in depressed patients in order to investigate the effect of rTMS on depression over 12 weeks after completion of the 2-week stimulation period . METHOD 55 patients with a moderate or severe DSM-IV major depressive episode were r and omly assigned to rTMS or sham treatment . rTMS was given daily for 10 days over the left dorsolateral prefrontal cortex with the following treatment parameters : 20 Hz , 20 trains of 2 seconds , 30 seconds between trains , and 80 % motor threshold . The effect of rTMS on depression was rated repeatedly with the 17-item Hamilton Rating Scale for Depression ( HAM-D ) during the 2-week period of stimulation and the 12-week follow-up period conducted from 1997 to 2001 . RESULTS We found a modest , clinical ly nonrelevant decrease in HAM-D scores in both rTMS and sham patients over 2 weeks of treatment . However , over the subsequent 12-week follow-up , the rTMS group continued to improve significantly compared with the placebo group . CONCLUSION Decrease of depressive symptoms may continue after the cessation of rTMS stimulation 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 
    Output:
    
Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy , but not with age , gender and sham method utilized .
/ SIGNIFICANCE We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination ( add-on rTMS studies ) .
The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself