***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: Despite many pharmacological and psychosocial treatment options , schizophrenia remains a debilitating disorder . Thus , new treatment strategies rooted in the pathophysiology of the disorder are needed . Recently , vagus nerve stimulation ( VNS ) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia . The objective of this study was to investigate for the first time the feasibility , safety and efficacy of transcutaneous VNS in stable schizophrenia . A bicentric r and omized , sham-controlled , double-blind trial was conducted from 2010 to 2012 . Twenty schizophrenia patients were r and omly assigned to one of two treatment groups . The first group ( active tVNS ) received daily active stimulation of the left auricle for 26 weeks . The second group ( sham tVNS ) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation . Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12 . Various other secondary measures were assessed to investigate safety and efficacy . The intervention was well tolerated with no relevant adverse effects . We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period . Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups . Application of tVNS was well tolerated , but did not improve schizophrenia symptoms in our 26-week trial . While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia , the overall pattern of symptom change might warrant further investigations in this 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 BACKGROUND Chronic vagus nerve stimulation ( VNS ) is effective in the management of treatment-resistant epilepsy . Open-trial evidence suggests that VNS has clinical ly significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes . However , limited information regarding the effects of VNS on neurocognitive performance exists . OBJECTIVE The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration . METHOD A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS .  Thirteen neurocognitive tests sample d the domains of motor speed , psychomotor function , language , attention , memory , and executive function . RESULTS No evidence of deterioration in any neurocognitive measure was detected . Relative to baseline , improvement in motor speed ( finger tapping ) , psychomotor function ( digit-symbol test ) , language ( verbal fluency ) , and executive functions ( logical reasoning , working memory , response inhibition , or impulsiveness ) was found . For some measures , improved neurocognitive performance correlated with the extent of reduction in depressive symptoms , but VNS output current was not related to changes in cognitive performance . CONCLUSIONS Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function , primarily among patients who show clinical improvement . Controlled investigation is needed to rule out the contribution of practice effects 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 TRD patients , although some patients required several months to obtain clinical improvement or remission of symptomatology . Nonetheless this procedure can be considered as a useful option in treating TRD BACKGROUND Vagus nerve stimulation ( VNS ) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders . An open trial has suggested efficacy . METHODS This 10-week , acute , r and omized , controlled , masked trial compared adjunctive VNS with sham treatment in 235 out patients with nonpsychotic major depressive disorder ( n = 210 ) or nonpsychotic , depressed phase , bipolar disorder ( n = 25 ) . In the current episode , participants had not responded adequately to between two and six research -qualified medication trials . A two-week , single-blind recovery period ( no stimulation ) and then 10 weeks of masked active or sham VNS followed implantation . Medications were kept stable . Primary efficacy outcome among 222 evaluable participants was based on response rates ( > /=50 % reduction from baseline on the 24-item Hamilton Rating Scale for Depression [ HRSD(24 ) ] ) . RESULTS At 10-weeks , HRSD(24 ) response rates were 15.2 % for the active ( n = 112 ) and 10.0 % for the sham ( n = 110 ) groups 
    Output:
    
At this point , no final conclusion can be made regarding the efficacy of VNS  to improve symptoms in psychiatric disorders other than in affective disorders