***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: OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of acute quetiapine monotherapy in adolescents with schizophrenia . METHODS Patients ages 13 - 17 years with an American Psychiatric Association , Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , Text Revision ( DSM-IV-TR ) diagnosis of schizophrenia and a Positive and Negative Syndrome Scale ( PANSS ) total score ≥60 were r and omized to 6 weeks of quetiapine ( 400 or 800 mg/day ) or placebo treatment . The primary efficacy measure was change in PANSS total score from baseline to day 42 . Safety endpoints included adverse events and assessment s of clinical chemistry values , suicidality , and extrapyramidal symptoms . RESULTS The intent-to-treat population included 220 patients . Least-squares mean change in PANSS total score from baseline to endpoint was -27.31 with quetiapine 400 mg/day , -28.44 with quetiapine 800 mg/day , and -19.15 with placebo ( p=0.043 and 0.009 for quetiapine 400 and 800 mg/day , respectively , vs. placebo ; mixed-model , repeated- measures analysis ) . Several secondary efficacy outcomes , including Clinical Global Impressions-Improvement score , supported the primary outcome measure in demonstrating significantly greater improvement in quetiapine groups than in the placebo group . Mean changes in body weight at day 42 were 2.2 kg and 1.8 kg for quetiapine 400 and 800 mg/day , respectively , and -0.4 kg for placebo . Mean changes in certain clinical chemistry parameters , including total cholesterol and triglycerides , were numerically greater in the quetiapine groups than in the placebo group . Adverse events associated with quetiapine were mostly mild to moderate in intensity and were consistent with its known profile in adults with schizophrenia . CONCLUSIONS In this 6-week study of adolescent patients  , quetiapine at doses of 400 and 800 mg/day provided significant improvements in symptoms associated with schizophrenia in adolescent patients , including the primary efficacy measure of PANSS total score change . Quetiapine was generally well tolerated with a profile broadly similar to that reported in adult and adolescent population s. CLINICAL TRIAL REGISTRATION INFORMATION Quetiapine Fumarate ( SEROQUEL ( ™ ) ) Compared to Placebo in the Treatment of Adolescent Patients With Schizophrenia ( ANCHOR 112 ) . Available at : http://www . clinical trials.gov/ct2/show/NCT00090324?term=quetiapine+112&rank=1 OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable , obese , or overweight patients with schizophrenia or schizoaffective disorder . Patients receiving olanzapine were r and omized to continuing olanzapine treatment ( N = 68 ; 7.5–20 mg/day ) or switching to  quetiapine ( N = 65 ; 300–800 mg/day ) . Time to relapse was the primary study objective ; secondary objectives included changes in weight , metabolic parameters , and psychiatric symptoms , and discontinuation rates . No significant difference in time to relapse was observed ( p = 0.293 ) , but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group ( 70.6 % vs 43.1 % ; p = 0.002 ) . Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events ( AEs ) compared to quetiapine ( 2.94 % vs 15.38 % , p = 0.015 ) . Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m2 . Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13 . Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse , but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials OBJECTIVE Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for design ing and interpreting research studies . Available dosing guidelines are limited by the methods and data from which they were generated . METHOD With a two-step Delphi method , the authors surveyed a diverse group of international clinical and research experts , seeking consensus regarding antipsychotic dosing . The authors determined median clinical dosing equivalents and recommended starting , target range , and maximum doses for 61 drugs , adjusted for selected clinical circumstances . RESULTS Participants ( N=43 ) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents . With olanzapine 20 mg/day as reference , estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol . Seventeen patient and treatment characteristics , including age , hepatic and renal function , illness stage and severity , sex , and diagnosis , were associated with dosing modifications . CONCLUSIONS In the absence of adequate prospect i ve , r and omized drug-drug comparisons , the present findings provide broad , international , expert consensus-based recommendations for most clinical ly employed antipsychotic drugs . They can support clinical practice , trial design , and interpretation of comparative antipsychotic trials OBJECTIVE  Placebo response and the rate of failed clinical trials are increasing in schizophrenia , resembling previous experience with antidepressant clinical trials . In depression , the percent of patients r and omized to placebo was shown to be strongly associated with drug-placebo differences ( signal detection).We hypothesized that this factor would also be important in recent schizophrenia clinical trials . To test this hypothesis a data base of acute schizophrenia placebo-controlled studies conducted between 1997 and 2008 was constructed . The data base contained 27 studies , with 79 active treatment arms . As percentage of patients r and omized to placebo increased , mean placebo improvement decreased ( p = 0.047 ) and mean drug-placebo differences tended to increase ( p = 0.166 ) . The frequency of significant contrasts from studies with ≥ 25 % r and omized to placebo was 83.3 % , compared with 58.3 % in studies with < 25 % r and omized to placebo . Caveats to these findings include limited data and confounding of potentially influential factors . These limitations prevent definitive conclusions . However , results are consistent with previous findings in depression where having a higher percent of patients r and omized to placebo increased drug-placebo differences OBJECTIVES This study aim ed to demonstrate efficacy of once-daily extended release quetiapine fumarate ( quetiapine XR ) versus placebo in patients with acute schizophrenia . METHODS In this 6-week , r and omized , double-blind study ( 5077IL/0041 ) patients were r and omized to receive quetiapine XR ( 300 , 600 , or 800 mg/day ) , quetiapine fumarate immediate release ( quetiapine IR ) [ 300 or 600 mg/day ] , or placebo . Primary endpoint was change from baseline in the Positive and Negative Syndrome Scale ( PANSS ) total score at Day 42 . Secondary variables included PANSS response rate at Day 42 ( > /=30 % decrease in PANSS total score from baseline ) and Clinical Global Impressions Severity ( CGI-S ) and Improvement ( CGI-I ) ratings . Safety assessment s included adverse event ( AE ) reporting and laboratory measures . RESULTS Of 532 patients r and omized , 222 ( 41.7 % ) completed the study . Improvements in PANSS total scores from baseline to Day 42 across treatment groups were : quetiapine XR 300 mg/day -5.01 , 600 mg/day -13.01 and 800 mg/day -11.17 , quetiapine IR 300 mg/day -9.42 and 600 mg/day -6.97 , and placebo -5.19 ; the difference in change was statistically significant only for quetiapine XR 600 mg/day ( p = 0.033 ) . There were no statistically significant differences between active treatment groups and placebo for PANSS response rates . Several post hoc analyses were conducted to explain the study efficacy outcome but these were inconclusive . Quetiapine XR was generally well tolerated with the majority of AEs being mild or moderate in intensity and no unexpected AEs . CONCLUSIONS Superior efficacy of quetiapine XR versus placebo in patients with schizophrenia was demonstrated for quetiapine XR 600 mg/day . The safety and tolerability profile of quetiapine XR was similar to that of quetiapine IR BACKGROUND Current antipsychotics have only a limited effect on 2 core aspects of schizophrenia : negative symptoms and cognitive deficits .  Minocycline is a second-generation tetracycline that has a beneficial effect in various neurologic disorders . Recent findings in animal models and human case reports suggest its potential for the treatment of schizophrenia . These findings may be linked to the effect of minocycline on the glutamatergic system , through inhibition of nitric oxide synthase and blocking of nitric oxide-induced neurotoxicity . Other proposed mechanisms of action include effects of minocycline on the dopaminergic system and its inhibition of microglial activation . OBJECTIVE To examine the efficacy of minocycline as an add-on treatment for alleviating negative and cognitive symptoms in early-phase schizophrenia . METHOD A longitudinal double-blind , r and omized , placebo-controlled design was used , and patients were followed for 6 months from August 2003 to March 2007 . Seventy early-phase schizophrenia patients ( according to DSM-IV ) were recruited and 54 were r and omly allocated in a 2:1 ratio to minocycline 200 mg/d  . All patients had been initiated on treatment with an atypical antipsychotic < or = 14 days prior to study entry ( risperidone , olanzapine , quetiapine , or clozapine ; 200 - 600 mg/d  chlorpromazine 
    Output:
    
Quetiapine IR caused sedation and increased rates of clinical ly significant weight gain , but no extrapyramidal effects were observed .
CONCLUSIONS Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2 - 12 weeks , but also leads to weight gain and sedation