You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Randomized, Double-blind 6-Month Comparison of Olanzapine and Quetiapine in Patients With Schizophrenia or Schizoaffective Disorder With Prominent Negative Symptoms and Poor Functioning
Abstract 1:
Abstract : This study compared the effects of olanzapine ( OLZ ) with those of quetiapine ( QUE ) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning . In this 6-month , multicenter , double-blind clinical trial , patients were r and omized to treatment with OLZ ( n = 171 , 10 - 20 mg/d ) or QUE ( n = 175 , 300 - 700 mg/d ) . Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans . The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms . Secondary measures assessed changes in functioning , psychopathology , and treatment tolerability . Treatment with OLZ or QUE led to a significant reduction in negative symptoms , with no between-group difference ( P = 0.09 ) . Both treatment groups also showed significant improvement on most efficacy measures .  Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale , Quality of Life Instrumental Role domain , and level of effort in psychosocial or occupational rehabilitation programs . Significantly more OLZ-treated patients completed the study ( 52.6 % OLZ , 37.7 % QUE , P = 0.007 ) . Treatment differences in safety were relatively small and not thought to be clinical ly relevant . Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE . Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy


Title 2:
A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia
Abstract 2:
Background Bitopertin , a glycine reuptake inhibitor , was investigated as a novel treatment for schizophrenia . We report all the results of a double-blind r and omized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia . Methods This study enrolled Japanese out patients with schizophrenia who met criteria for either “ negative symptoms ” , i.e. , patients with persistent , predominant negative symptoms of schizophrenia even after long-term treatment with antipsychotics or “ sub-optimally controlled symptoms ” , i.e. , patients with insufficiently improved symptoms of schizophrenia even after long-term treatment with antipsychotics , respectively . One hundred sixty-one patients were r and omly assigned to receive 52-week treatments with bitopertin doses of 5 , 10 , or 20 mg/day at ratio of 1:5:5 , where existing antipsychotics were concomitantly administered . Efficacy endpoints included Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression ( CGI ) , and Personal and Social Performance ( PSP ) . The purpose of the present study is primarily to evaluate the safety , and secondarily to investigate the clinical efficacy of bitopertin . Results One hundred fourteen patients ( 71 % ) completed 52-week treatment with bitopertin . Most of the adverse events were mild or moderate in their severity . The patients in the 20-mg group experienced more adverse events than the patients in the other two groups . Common dose-dependent adverse events were somnolence and insomnia associated with worsening schizophrenia . The blood hemoglobin levels gradually decreased from baseline in a dose-dependent manner , but there were no patients with the decrease below 10 g/dL that would have led to their discontinuation . All the efficacy endpoints gradually improved in all the treatment groups for both of the two symptoms , while there were no clear differences among the three dose groups . Conclusions Altogether , bitopertin was found to be generally safe and well-tolerated for the treatment of patients with schizophrenia . All three bitopertin treated groups showed improvements in all the efficacy endpoints for both of the two symptoms , i.e. , “ negative symptoms ” and “ sub-optimally controlled symptoms ” , throughout the duration of the study .Trial registration Japan Pharmaceutical Information Center , number JapicCTI-111627 ( registered on September 20 , 2011


Title 3:
Application and Results of the Manchester Short Assessment of Quality of Life (Mansa)
Abstract 3:
Background Based on experiences and empirical evidence gained in studies using the Lancashire Quality of Life Profile ( LQLP ) , the Manchester Short Assessment of Quality of Life ( MANSA ) has been developed as a condensed and slightly modified instrument for assessing quality of life . Its properties have been tested in a sample of community care patients . Method Fifty-five r and omly selected patients on the Care Programme Approach were interviewed using the LQLP , the MANSA and the Brief Psychiatric Rating Scale .  Results Correlations between subjective quality of life scores on MANSA and LQLP were all 0.83 or higher ( 0.94 for the satisfaction mean score ) . Cronbach 's alpha for satisfaction ratings was 0.74 , and association with psychopathology was in line with results for LQLP as reported in the literature . Conclusions The MANSA is a brief instrument for assessing quality of life focusing on satisfaction with life as a whole and with life domains . Its psychometric properties appear satisfactory


Title 4:
Development and validation of a patient-based health-related quality of life questionnaire in schizophrenia: the S-QoL
Abstract 4:
We developed a self-administered instrument to assess  health-related quality of life ( HRQL ) among people with schizophrenia . The S-QoL , based on Calman 's approach to the subject 's point of view , is a multidimensional instrument that is sensitive to change . The scale is a 41-item question naire with eight subscales ( psychological well-being , self-esteem , family relationships , relationships with friends , resilience , physical well-being , autonomy and sentimental life ) and a total score . In-depth interviews with patients determined the pertinent issues for item development . The validation study , performed with 207 patients , showed high internal consistency reliability , reproducibility and responsiveness . Construct validity was confirmed using established clinical and HRQL measures . S-QoL covers domains that differ from areas tapped in other measures , with greater responsiveness . The S-QoL is an efficient instrument for the measurement of the impact of schizophrenia  on individuals ' lives


Title 5:
Improvement of schizophrenic patients’ subjective well-being under atypical antipsychotic drugs
Abstract 5:
Recent research indicates that subjective well-being is a major determinant of medication compliance in schizophrenia . However , it is yet unresolved whether atypical neuroleptics differ regarding subjective side-effects . A self-report instrument has been constructed to evaluate ' subjective well-being under neuroleptics  ' ( SWN ) . The primary aims of the present study were to develop a short form of the SWN and to investigate the extent to which the atypical antipsychotic improves the patient 's subjective well-being . The short form of the SWN was constructed following an item analysis based on data from 212 schizophrenic patients medicated with either typical or atypical antipsychotics .  The short form of the SWN showed sufficient internal consistency and good construct validity . The SWN was only moderately correlated with positive and negative syndrome scale ( PANSS ) scores or changes in psychopathology ( r=-0.20 to -0.37 ) . SWN-ratings in patients receiving olanzapine were superior compared to those of patients medicated with either clozapine or risperidone on three of five domains of well-being . Clozapine reduced global psychiatric symptoms significantly more than risperidone . It is concluded that the assessment of subjective well-being under antipsychotic treatment provides an independent outcome measure which is relevant to compliance


Title 6:
Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study
Abstract 6:
Current meta- analysis revealed small , but significant effects of repetitive transcranial magnetic stimulation ( rTMS ) on negative symptoms in patients with schizophrenia . There is a need for further controlled , multicenter trials to assess the clinical efficacy of rTMS on negative symptoms in schizophrenia in a larger sample of patients . The objective of this multicenter , r and omized , sham-controlled , rater- and patient-blind clinical trial is to investigate the efficacy of 3-week 10-Hz high frequency rTMS add on to antipsychotic therapy , 15 sessions per 3 weeks , 1,000 stimuli per session , stimulation intensity 110 % of the individual motor threshold ) of the left dorsolateral prefrontal cortex for treating negative symptoms in schizophrenia , and to evaluate the effect during a 12 weeks of follow-up . The primary efficacy endpoint is a reduction of negative symptoms as assessed by the negative sum score of the positive and negative symptom score ( PANSS ) .  A sample size of 63 in each group will have 80 % power to detect an effect size of 0.50 . Data analysis will be based on the intention to treat population . The study will be conducted at three university hospitals in Germany . This study will provide information about the efficacy of rTMS  in the treatment of negative symptoms . In addition to psychopathology , other outcome measures such as neurocognition , social functioning , quality of life and neurobiological parameters will be assessed to investigate basic mechanisms of rTMS in schizophrenia . Main limitations of the trial are the potential influence of antipsychotic dosage changes and the difficulty to ensure adequate blinding


Title 7:
The Selective Glycine Uptake Inhibitor Org 25935 as an Adjunctive Treatment to Atypical Antipsychotics in Predominant Persistent Negative Symptoms of Schizophrenia: Results From the GIANT Trial
Abstract 7:
Abstract Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic ( SGA ) was hypothesized to ameliorate negative and /or cognitive symptoms in subjects with schizophrenia . Subjects with predominant persistent negative symptoms ( previously stabilized ≥3 months on an SGA ) were enrolled in a r and omized , placebo-controlled trial to investigate adjunctive treatment with Org 25935 , a selective inhibitor of type 1 glycine transporter , over 12 weeks in a flexible dose design . Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo . Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score . Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores , depressive symptoms ( Calgary Depression Scale for Schizophrenia ) , global functioning ( Global Assessment of Functioning scale ) , and cognitive measures using a computerized battery ( Central Nervous System Vital Signs ) . Responder rates were assessed post hoc . A total of 215 subjects were r and omized , of which 187 ( 87 % ) completed the trial . Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms , Positive and Negative Syndrome Scale ( total or subscale scores ) , Global Assessment of Functioning , or the majority of tested cognitive domains .  Org 25935 was generally well tolerated within the tested dose range , with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects . Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA . In our study population , Org 25935 appeared to be well tolerated in the tested dose ranges


Title 8:
Identifying clinically meaningful symptom response cut-off values on the SANS in predominant negative symptoms
Abstract 8:
BACKGROUND The treatment and measurement of negative symptoms are currently at issue in schizophrenia , but the clinical meaning of symptom severity and change is unclear . AIM To offer a clinical ly meaningful interpretation of severity and change scores on the Scale for the Assessment of Negative Symptoms ( SANS ) . METHOD Patients were intention-to-treat participants ( n=383 ) in two double-blind r and omized placebo-controlled clinical trials that compared amisulpride with placebo for the treatment of predominant negative symptoms . Equipercentile linking was used to examine extrapolation from ( a ) CGI-S to SANS severity ratings , and ( b ) CGI-I to SANS percentage change ( n=383 ) . Linking was conducted at baseline , 8 - 14 days , 28 - 30 days , and 56 - 60 days of the trials . RESULTS Across visits , CGI-S ratings of ' not ill ' linked to SANS scores of 0 - 13 , and ranged to ' extreme ' ratings that linked to SANS scores of 102 - 105 . The relationship between the CGI-S and the SANS severity scores assumed a linear trend ( 1=0 - 13 , 2=15 - 56 , 3=37 - 61 , 4=49 - 66 , 5=63 - 75 , 6=79 - 89 , 7=102 - 105 ) . Similarly the relationship between CGI-I ratings and SANS percentage change followed a linear trend . For instance , CGI-I ratings of ' very much improved ' were linked to SANS percent changes of -90 to -67 , ' much improved ' to -50 to -42 , and ' minimally improved ' to -21 to -13 . CONCLUSIONS The current results uniquely contribute to the debate surrounding negative symptoms by providing clinical meaning to SANS severity and change scores and so offer direction regarding clinical ly meaningful response cut-off scores to guide treatment targets of predominant negative symptoms
Conclusion : No HRQoL instrument has been vali date d in patients with SNS only ; for the remaining instruments identified , it remains unclear whether they were intended to capture HRQoL in patients with SNS