***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 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 OBJECTIVE The Treatment-Resistant Depression Registry investigated whether adjunctive vagus nerve stimulation ( VNS ) with treatment as usual in depression has superior long-term outcomes compared with treatment as usual only . METHOD This 5-year , prospect i ve , open-label , nonr and omized , observational registry study was conducted at 61 U.S. sites and included 795 patients who were experiencing a major depressive episode ( unipolar or bipolar depression ) of at least 2 years ' duration or had three or more depressive episodes ( including the current episode ) , and who had failed four or more depression treatments ( including ECT ) . Patients with a history of psychosis or rapid-cycling bipolar disorder were excluded . The primary efficacy measure was response rate , defined as a decrease of ≥50 % in baseline Montgomery-Åsberg Depression Rating Scale ( MADRS ) score at any postbaseline visit during the 5-year study . Secondary efficacy measures included remission . RESULTS Patients had chronic moderate to severe depression at baseline ( the mean MADRS score was 29.3 [ SD=6.9 ] for the treatment-as-usual group and 33.1 [ SD=7.0 ] for the adjunctive VNS group ) . The registry results indicate that the adjunctive VNS group had better clinical outcomes than the treatment-as-usual group , including a significantly higher 5-year cumulative response rate ( 67.6 % compared with 40.9 % ) and a significantly higher remission rate ( cumulative first-time remitters , 43.3 % compared with 25.7 % ) . A sub analysis demonstrated that among patients with a history of response to ECT , those in the adjunctive VNS group had a significantly higher 5-year cumulative response rate than those in the treatment-as-usual group ( 71.3 % compared with 56.9 % ) . A similar significant response differential was observed among ECT nonresponders ( 59.6 % compared with 34.1 % ) . CONCLUSIONS This registry represents the longest and largest naturalistic study of efficacy outcomes in treatment-resistant depression , and it provides additional evidence that adjunctive VNS has enhanced antidepressant effects compared with treatment as usual in this severely ill patient population BACKGROUND The need for effective , long-term treatment for recurrent or chronic , treatment-resistant depression is well established . METHODS This naturalistic follow-up describes out patients with nonpsychotic major depressive ( n = 185 ) or bipolar ( I or II ) disorder , depressed phase ( n = 20 ) who initially received 10 weeks of active ( n = 110 ) or sham vagus nerve stimulation ( VNS ) ( n = 95 ) . The initial active group received another 9 months , while the initial sham group received 12 months of VNS .  Participants received antidepressant treatments and VNS , both of which could be adjusted . RESULTS The primary analysis ( repeated measures linear regression ) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression ( HRSD(24 ) ) scores ( average improvement , .45 points [ SE = .05 ] per month ( p < .001 ) . At exit , HRSD(24 ) response rate was 27.2 % ( 55/202 ) ; remission rate ( HRSD(24 ) < or = 9 ) was 15.8 % ( 32/202 ) . Montgomery Asberg Depression Rating Scale ( 28.2 % [ 57/202 ] ) and Clinical Global Impression-Improvement ( 34.0 % [ 68/200 ] ) showed similar response rates . Voice alteration , dyspnea , and neck pain were the most frequently reported adverse events . CONCLUSIONS These 1-year open trial data found VNS to be well tolerated , suggesting a potential long-term , growing benefit in treatment-resistant depression , albeit in the context of changes in depression treatments . Comparative long-term data are needed to determine whether these benefits can be attributed to VNS OBJECTIVE To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation ( VNS )  following US Food and Drug Administration ( FDA ) approval of this intervention . METHOD We implanted a VNS device in 15 consecutive out patients with treatment-resistant major depressive episodes , including 10 with major depressive disorder and 5 with bipolar disorder ( DSM-IV criteria ) , between November 2005 and August 2006 . Existing antidepressant treatment remained fixed as far as clinical ly possible . The primary outcome was change from baseline in the Beck Depression Inventory ( BDI ) score . Outcomes were assessed at 6 and 12 months postimplant and compared to those of the VNS pivotal efficacy trial that led to FDA approval of VNS . RESULTS The BDI score decreased significantly compared to baseline at 6 months ( P < .05 ) and 12 months ( P < .01 ) , from a mean of 37.8 ( SD = 7.8 ) before VNS activation to a mean of 24.6 ( SD = 11.4 ) at 12 months . By 1 year , 28.6 % ( n = 4 ) of the sample responded to VNS and 7.1 % ( n = 1 ) remitted according to the BDI . Secondary outcomes on the Hamilton Depression Rating Scale 24-Item showed similar improvement at 1 year , with a 43 % response rate ( n = 6 ) and 14.3 % remission rate ( n = 2 ) . No obvious predictors of response were detected . Side effects of VNS included hoarseness ( 73 % ) , dyspnea ( 47 % ) , nausea ( 40 % ) , pain ( 33 % ) , and anxiety ( 20 % ) ; no patient terminated treatment due to intolerable side effects . CONCLUSIONS We found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice , with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile BACKGROUND Major depressive disorder is a prevalent , disabling , and often chronic or recurrent psychiatric condition . About 35 % of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression ( TRD ) . OBJECTIVE We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation ( VNS ) therapy for the treatment of TRD . METHODS In a multicenter , double blind study , 331 patients with TRD were r and omized to one of three dose groups : LOW ( 0.25 mA current , 130 μs pulse width ) , MEDIUM ( 0.5 - 1.0 mA , 250 μs ) , or HIGH ( 1.25 - 1.5 mA , 250 μs ) . A highly treatment-resistant population ( > 97 % had failed to respond to ≥6 previous treatments ) was enrolled . Response and adverse effects were assessed for 22 weeks ( end of acute phase ) , after which output current could be increased , if clinical ly warranted . Assessment s then continued until Week 50 ( end of long-term phase ) . RESULTS VNS therapy was well tolerated . During the acute phase , all groups showed statistically significant improvement on the primary efficacy endpoint ( change in Inventory of Depressive Symptomatology-Clinician Administered Version [ IDS-C ] ) , but not for any between-treatment group comparisons . In the long-term phase , mean change in IDS-C scores showed continued improvement . Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms ; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose . CONCLUSIONS TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline , and the effect was durable over 1 year . Higher electrical dose parameters were associated with response durability This open pilot study of vagus nerve stimulation ( VNS ™ ) in 60 patients with treatment-resistant major depressive episodes ( MDEs ) aim ed to : 1 ) define the response rate ; 2 ) determine the profile of side effects ; and , most importantly ; 3 ) establish predictors of clinical outcome . Participants were out patients with nonatypical , nonpsychotic , major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE . While on stable medication regimens , the patients completed a baseline period followed by device implantation . A 2-week , single blind , recovery period ( no stimulation ) was followed by 10 weeks of VNS . Of 59 completers ( one patient improved during the recovery period ) , the response rate was 30.5 % for the primary HRSD28 measure , 34.0 % for the Montgomery-Äsberg Depression Rating Scale ( MADRAS ) , and 37.3 % for the Clinical Global Impression-Improvement Score ( CGI-I of 1 or 2 ) . The most common side effect was voice alteration or hoarseness , 55.0 % ( 33/60 ) , which was generally mild and related to output current intensity . History of treatment resistance was predictive of VNS outcome . Patients who had never received ECT ( lifetime ) were 3.9 times more likely to respond . Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE , none responded , compared to 39.1 % of the remaining 46 patients ( p = .0057 ) . Thus , VNS appears to be most effective in patients with low to moderate , but not extreme , antidepressant resistance . Evidence concerning VNS  ' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression AIM The purpose of this study was to evaluate the efficacy of vagus nerve stimulation ( VNS ) as a therapeutic option for treatment-resistant depression ( TRD ) , with follow-up periods of 1 , 3 and 5 years after VNS surgery . METHODS We examined 27 consecutive patients with unipolar TRD .  Depressive symptoms were evaluated both at baseline and at follow-up after the surgery by means of the 21-item Hamilton Rating Scale for Depression ( HAM-D 21 ) . RESULTS The mean HAM-D preoperative score was 25.6 . Twenty-two patients were evaluated after 1 year of treatment , and the mean improvement of the HAM-D score was of 10.3 . Five patients ( 20 % ) went into complete remission ( HAM-D < 7 ) after 1 year , six patients ( 22.3 % ) were considered responders ( 50 % reduction of HAM-D scoring ) and eight patients had score reduction of less then 20 % . Nineteen patients were evaluated after 24–36 months : the average improvement on the HAM-D score was of 12.1 points ( 47.2 % ) . One patient went into complete remission and eight patients ( 42.1 % ) were responders . Up to the present date , seven patients have undergone re-evaluation at 48–60 months from surgery showing an average score reduction of 14.2 . Two more patients obtained complete remission , while four of them did not have any improvement since their last follow-up control visit . CONCLUSION VNS antidepressant was successful in 20 % of 
    Output:
    
Analyses demonstrated that antidepressant benefits improved to 24 months and safety issues were minimal .
Despite limitations in the evidence base , our comprehensive summary of VNS+TAU outcomes suggests that this treatment provides improving benefit and hope for this very hard-to-treat chronic population .