***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 
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    Input: OBJECTIVES A growing number of atypical antipsychotics are available for clinicians to choose from in the treatment of psychotic disorders . However , a number of important questions concerning medication selection , dosing and dose equivalence , and the management of inadequate response , compliance problems , and relapse have not been adequately addressed by clinical trials . To aid clinical decision-making , a consensus survey of expert opinion on the pharmacologic treatment of psychotic disorders was undertaken to address questions not definitively answered in the research literature . METHOD Based on a literature review , a written survey was developed with 60 questions and 994 options . Approximately half of the options were scored using a modified version of the R AND 9-point scale for rating the appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or check a box to indicate their preferred answer . The survey was sent to 50 national experts on the pharmacologic treatment of psychotic disorders , 47 ( 94 % ) of whom completed it . In analyzing the responses to items rated on the 9-point scale , consensus on each option was defined as a non r and om distribution of scores by chi-square " goodness-of-fit"test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 88 % of the options rated on the 9-point scale . The experts overwhelmingly endorsed the atypical antipsychotics for the treatment of psychotic disorders . Risperidone was the top choice for first-episode and multi-episode patients , with the other newer atypicals rated first line or high second line depending on the clinical situation . Clozapine and a long-acting injectable atypical ( when available)were other high second line options for multi-episode patients . The expert 's dosing recommendations agreed closely with the package inserts for the drugs , and their estimates of dose equivalence among the antipsychotics followed a linear pattern . The experts considered 3 - 6 weeks an adequate antipsychotic trial , but would wait a little longer ( 4 - 10 weeks ) before making a major change in treatment regimen if there is a partial response . The experts recommended trying to improve response by increasing the dose of atypical and depot antipsychotics before switching to a different agent ; there was less agreement about increasing the dose of conventional antipsychotics before switching , probably because of concern about side effects at higher doses . If it is decided to switch because of inadequate response , risperidone was the expert 's first choice to switch to , no matter what drug was initially tried . Although there was some disparity in the expert 's recommendations concerning how many agents to try before switching to clozapine , the expert 's responses suggest that switching to clozapine should be Clozapine was also the antipsychotic of choice for patients with suicidal behavior . When switching oral antipsychotics , the experts considered cross-titration the preferred strategy . When switching to an injectable antipsychotic , the experts stressed the importance of continuing the oral antipsychotic until therapeutic levels of the injectable agent are achieved . The experts considered psychosocial interventions the first choice strategy for partially compliant patients , with pharmacologic interventions the first choice for patients with clear evidence of noncompliance . However , because it can be difficult to distinguish partially compliant from noncompliant patients , the editors recommended combining psychosocial and pharmacologic interventions to improve compliance whenever possible . When patients relapse because of compliance problems or if there is any doubt about compliance , the experts recommended the use of a long-acting injectable antipsychotic and would select an injectable atypical when this option becomes available . The experts would also consider using an injectable atypical antipsychotic ( when available ) in many clinical situations that do not involve compliance problems . The experts stressed the importance of monitoring for health problems-especially obesity , diabetes , cardiovascular problems , HIV risk behaviors , medical complications of substance abuse , heavy smoking and its effects , hypertension , and amenorrhea-in patients being treated with antipsychotics . Although many patients are prescribed adjunctive treatments , multiple antipsychotics , and combinations of different classes of drugs ( e.g. , antipsychotics plus mood stabilizers or antidepressants ) in an effort to enhance response , the experts gave little support to any of these strategies , with the exception of antidepressants for patients with  dysphoria/depression  , antidepressants or ECT for patients with suicidal behavior , and mood stabilizers for patients with aggression/violence . When asked about indicators of remission and recovery , the experts considered acute improvement in psychotic symptoms the most important indicator of remission , whereas they considered more sustained improvement in multiple outcome domains ( e.g. , occupational/educational functioning , peer relationships , independent living ) important in assessing recovery . CONCLUSIONS The experts reached a high level of consensus on many of the key treatment questions in the survey . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas that arise in the pharmacologic treatment of psychotic disorders . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Clinicians should keep in mind that no guidelines can address the complexities involved in the care of each individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations Clozapine is the only available therapy for about 30 % of schizophrenia patients otherwise refractory to antipsychotics . Unfortunately , the mechanism of action of the drug is still unknown and there are no biomarkers that can predict a positive response to clozapine . We aim ed to examine serum neurotrophins and glutamate levels as putative biomarkers for clozapine response based on the hypothesized mode-of-action of the compound . Blood sample s of 89 chronic schizophrenia patients maintained on clozapine  were analyzed in a cross-sectional design . Serum brain derived neurotrophic factor ( BDNF ) , vascular endothelial growth factor ( VEGF ) , neurotrophic growth factor ( NGF ) , glial derived neurotrophic factor ( GDNF ) and glutamate were determined . Differences between responders and non-responders to clozapine and correlation between clinical and biological measures were analyzed . Our sample consisted of 54 ( 61 % ) responders and 35 ( 39 % ) non-responders . Responders had higher mean BDNF levels than non-responders ( 2066±814 vs. 1668±820pg/ml , p<0.05 . respectively ) and higher serum glutamate levels ( 1.61±2.2 vs. 0.66±0.9pg/ml , respectively , p<0.05 ) . Furthermore , there was a significant correlation between serum glutamate levels and positive symptoms among the clozapine-responder group ( rho=0.47 , p<0.005 ) . High serum levels of BDNF and glutamate were associated with response to clozapine , while glutamate levels correlated with the psychosis severity in clozapine responders only . Large-scale , prospect i ve longitudinal studies are needed to support these findings and the assumption that serum glutamate and BDNF can discriminate between clozapine responders and non-responders OBJECTIVE Maintenance treatment of schizophrenia with antipsychotic medications has become a st and ard for the prevention of psychotic relapse . However , little is known about the effectiveness of antipsychotic drugs for maintenance treatment in " real-world " population s with schizophrenia . We carried out a prospect i ve study to assess the effectiveness of the most frequently prescribed antipsychotic drugs in the maintenance treatment of schizophrenia from 2 community setting s. METHODS This study was conducted from October 2011 to December 2014 . All participants were diagnosed with schizophrenia according to DSM-IV , were treated with an antipsychotic monotherapy , and were registered in a case management program with monthly monitoring for 24 months . The primary outcome measure , Positive and Negative Syndrome Scale ( PANSS ) , and the Clinical Global Impressions-Severity of Illness ( CGI-S ) and -Improvement ( CGI-I ) scales were used to evaluate symptom severity and treatment response . The Personal and Social Performance scale ( PSP ) was used to evaluate the patients ' social functioning . The Medication Adherence Rating Scale ( MARS ) was used to assess medication adherence behavior . On the basis of antipsychotic used at baseline , patients were clustered into 7 groups : aripiprazole ( n = 21 ) , clozapine ( n = 84 ) , chlorpromazine ( n = 61 ) , olanzapine ( n = 34 ) , perphenazine ( n = 21 ) , quetiapine ( n = 27 ) , and risperidone ( n = 99 ) . RESULTS Of the 347 patients enrolled in the study , 312 completed the 24-month follow-up . There were no significant differences among the treatment groups in the PANSS total and subscale scores or the CGI-S and CGI-I scores over 24 months ( all P values > .05 ) . There were also no significant differences in interactions between PSP scores and antipsychotic drugs ( P = .17 ) . The remission rates increased as the follow-time lapsed in all groups , but no significant difference was observed in remission rates at each time point among the 7 groups ( P values > .05 ) . At the endpoint , MARS total scores were over 6 , but did not significantly differ among the studied drugs ( P = .24 ) . CONCLUSIONS These findings suggest that antipsychotic drugs can achieve equivalent effectiveness in maintenance treatment of first-episode schizophrenia through a well-organized case management program and family participation OBJECTIVE To assess the relation between plasma concentrations of clozapine and its 2 main metabolites desmethyl clozapine and clozapine N-oxide , and clinical change in a sample of in patients with schizophrenia who were resistant to conventional neuroleptics . METHOD Thirty-seven patients ( 27 men and 10 women , mean age 34.8 yr ) with treatment-resistant schizophrenia were treated with clozapine for 18 weeks ; dosage was adjusted according to clinical response , and plasma concentrations of clozapine and of its metabolites were measured weekly by high-performance liquid chromatography .  Clinical status was also assessed weekly with the Positive and Negative Syndrome Scale ( PANSS ) . Patients were considered " responsive " if they showed at least a 20 % improvement over their baseline PANSS ratings . RESULTS The mean endpoint  clozapine dosage was 486.5 mg/day . There was a significant correlation between the daily dosage of clozapine  and the plasma levels of clozapine and of its metabolites ( p < 0.05 ) . There was no correlation between the  clozapine plasma level and the percent improvement on the PANSS . Clozapine plasma levels were not significantly different between those who responded to clozapine ( n = 19 ) and those who did not ( n = 18 ) and were not significantly different between patients who smoked ( n = 28 ) and those who did not ( n = 9 ) . Receiver operating characteristic ( ROC ) curve analysis determined the plasma level threshold ( above which a better clinical response was obtained ) to be 550 ng/mL. Using the total of plasma levels of clozapine and its metabolites did not lead to a better sensitivity and specificity . CONCLUSIONS Our calculated plasma clozapine threshold was higher than that reported by others , but this may be related to the severity of symptoms of our patient sample . Monitoring plasma rates remains a useful tool , together with clinical evaluation , to establish the clozapine dosage for an optimum benefit-risk ratio Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment . Patients from our early psychosis service who met the inclusion criteria ( n = 48 ) were r and omized to one of four treatment groups : clozapine , clozapine plus CBT , thioridazine , or thioridazine plus CBT . The degree of psychopathology and functionality of all participants was measured at baseline then again at 6 , 12 and 24 weeks , and the treatment outcomes for each group determined by statistical analysis . A substantial proportion ( 52 % ) of those treated with clozapine  achieved symptomatic remission , as compared to 35 % of those who were treated with thioridazine . Overall , those who received clozapine  responded more rapidly to treatment than those receiving the alternative treatments . Interestingly , during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment , as well having as a stabilizing effect over time This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications . A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry . Patients in the original study were r and omly assigned to haloperidol or clozapine and followed for 12 months , at maximum tolerable doses . Patients who completed a full year of treatment with clozapine ( n = 122 ) , or with either haloperidol 
    Output:
    
The results of our meta-analyses suggest that three baseline demographic and clinical features are associated with better  clozapine response , i.e. relatively young age , few negative symptoms and paranoid schizophrenia subtype .