human
***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 Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment . Functional brain correlates of this phenomenon have not been fully characterized . METHOD Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo  as part of an inpatient imaging study of fluoxetine . Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week , double-blind trial . RESULTS Placebo response was associated with regional metabolic increases involving the prefrontal , anterior cingulate , premotor , parietal , posterior insula , and posterior cingulate and metabolic decreases involving the subgenual cingulate , parahippocampus , and thalamus . Regions of change overlapped those seen in responders administered active fluoxetine . Fluoxetine response , however , was associated with additional subcortical and limbic changes in the brainstem , striatum , anterior insula , and hippocampus , sources of efferent input to the response-specific regions identified with both agents . CONCLUSIONS The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission , regardless of treatment modality . Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms . The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention OBJECTIVE For decades , lithium has been prescribed to treat bipolar disorder . Its efficacy has been documented by clinical trials and by data from specialized clinics . An issue of considerable interest is the use of lithium in managed care systems . This project examined the use of lithium and its continuity of use by enrollees of a health maintenance organization ( HMO ) . METHOD In a 6-year longitudinal cohort study , 1,594 lithium users aged 15 years and older who were enrolled in an HMO were followed from 1986 - 1991 . Data were obtained from automated data bases and from medical record review of a r and om 5 % sub sample of the group ( N = 74 ) . RESULTS Bipolar disorder was the most frequent morbidity treated . Eighty-four percent ( N = 62 or 74 ) received services from a psychiatrist . Annual prevalence of lithium use increased over the 6-year period from 1.4 to 2.3 persons per thous and HMO members . Duration of use varied widely with some long-term but many short-term users . Discontinuation of treatment was associated with evaluated rates of psychiatric hospitalization and use of psychiatric emergency services .  Lithium users were much more likely to receive a variety of other psychotropic drugs than nonusers of the same sex and age . CONCLUSIONS Lithium use in this population was more often sporadic than continuous . Discontinuation of lithium was associated with psychiatric hospitalization . If lithium is to be a cost-effective treatment for bipolar disorder , managed care systems will need to improve adherence to drug treatment regimens Maintenance studies in bipolar disorder have received increased attention in recent years . The interest is driven by apparent contradictions between results of early placebo-controlled trials of lithium and recent open studies , as well as interest in a new group of drugs with mood-stabilizing properties . The multiple outcome indices that require attention in prophylactic bipolar disorder studies add a dimension not present in acute studies of bipolar disorder . We present the methodology of a recently completed r and omized , double-blind , placebo-controlled , parallel-group comparison of divalproex and lithium . We examine the consequences of salient design features , along with their implication s for future studies . A fundamental conclusion is that such maintenance studies should be design ed and executed to emphasize enrollment of patients with relatively active , severe forms of the illness . This goal is not achieved simply , as inherent features of long-term , placebo-controlled studies drive recruitment and enrollment in the direction of patients with milder forms of bipolar disorder . Attention to the frequency of both manic and depressive episodes and the severity of an index manic episode may aid in the selection of patients most suitable for studies design ed to achieve adequate statistical power OBJECTIVE The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania . METHOD The design involved a r and om-assignment , double-blind , placebo-controlled parallel group study of 3 weeks ' duration . After a 2- to 4-day screening period , qualified patients were assigned to either olanzapine ( N = 70 ) or placebo ( N = 69 ) . Patients began double-blind therapy with either olanzapine , 10 mg , or placebo given once per day . After the first day of treatment , the daily dose could be adjusted upward or downward , as clinical ly indicated , by one capsule ( olanzapine , 5 mg/day ) within the allowed range of one to four capsules . The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale . Clinical response was defined a priori as a decrease of 50 % or more from baseline in Young Mania Rating Scale total score . RESULTS The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group . On the basis of the clinical response criteria , significantly more olanzapine-treated patients ( 48.6 % ) responded than those assigned to placebo ( 24.2 % ) . Somnolence , dizziness , dry mouth , and weight gain occurred significantly more often with olanzapine . There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism , akathisia , and dyskinesias . No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group . CONCLUSIONS The results from this study suggest that compared with placebo , olanzapine has superior efficacy for the symptoms of acute mania 
    Output:
    
agent
Placebo response in bipolar disorder trials is more likely to occur in patients who are mildly ill , bipolar II , mixed-episode , first-episode , rapid cycling , atypical , non-psychotic , substance abusers and medically ill .
The use of concomitant medication such as benzodiazepines , a high frequency of visits , a high number of treatment groups and sites , fixed-dose design s , and the concomitant use of psychotherapy are likely to increase placebo response .
There are a number of clinical and method ological variables that are associated with placebo response
***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 Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment . Functional brain correlates of this phenomenon have not been fully characterized . METHOD Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo  as part of an inpatient imaging study of fluoxetine . Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week , double-blind trial . RESULTS Placebo response was associated with regional metabolic increases involving the prefrontal , anterior cingulate , premotor , parietal , posterior insula , and posterior cingulate and metabolic decreases involving the subgenual cingulate , parahippocampus , and thalamus . Regions of change overlapped those seen in responders administered active fluoxetine . Fluoxetine response , however , was associated with additional subcortical and limbic changes in the brainstem , striatum , anterior insula , and hippocampus , sources of efferent input to the response-specific regions identified with both agents . CONCLUSIONS The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission , regardless of treatment modality . Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms . The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention OBJECTIVE For decades , lithium has been prescribed to treat bipolar disorder . Its efficacy has been documented by clinical trials and by data from specialized clinics . An issue of considerable interest is the use of lithium in managed care systems . This project examined the use of lithium and its continuity of use by enrollees of a health maintenance organization ( HMO ) . METHOD In a 6-year longitudinal cohort study , 1,594 lithium users aged 15 years and older who were enrolled in an HMO were followed from 1986 - 1991 . Data were obtained from automated data bases and from medical record review of a r and om 5 % sub sample of the group ( N = 74 ) . RESULTS Bipolar disorder was the most frequent morbidity treated . Eighty-four percent ( N = 62 or 74 ) received services from a psychiatrist . Annual prevalence of lithium use increased over the 6-year period from 1.4 to 2.3 persons per thous and HMO members . Duration of use varied widely with some long-term but many short-term users . Discontinuation of treatment was associated with evaluated rates of psychiatric hospitalization and use of psychiatric emergency services .  Lithium users were much more likely to receive a variety of other psychotropic drugs than nonusers of the same sex and age . CONCLUSIONS Lithium use in this population was more often sporadic than continuous . Discontinuation of lithium was associated with psychiatric hospitalization . If lithium is to be a cost-effective treatment for bipolar disorder , managed care systems will need to improve adherence to drug treatment regimens Maintenance studies in bipolar disorder have received increased attention in recent years . The interest is driven by apparent contradictions between results of early placebo-controlled trials of lithium and recent open studies , as well as interest in a new group of drugs with mood-stabilizing properties . The multiple outcome indices that require attention in prophylactic bipolar disorder studies add a dimension not present in acute studies of bipolar disorder . We present the methodology of a recently completed r and omized , double-blind , placebo-controlled , parallel-group comparison of divalproex and lithium . We examine the consequences of salient design features , along with their implication s for future studies . A fundamental conclusion is that such maintenance studies should be design ed and executed to emphasize enrollment of patients with relatively active , severe forms of the illness . This goal is not achieved simply , as inherent features of long-term , placebo-controlled studies drive recruitment and enrollment in the direction of patients with milder forms of bipolar disorder . Attention to the frequency of both manic and depressive episodes and the severity of an index manic episode may aid in the selection of patients most suitable for studies design ed to achieve adequate statistical power OBJECTIVE The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania . METHOD The design involved a r and om-assignment , double-blind , placebo-controlled parallel group study of 3 weeks ' duration . After a 2- to 4-day screening period , qualified patients were assigned to either olanzapine ( N = 70 ) or placebo ( N = 69 ) . Patients began double-blind therapy with either olanzapine , 10 mg , or placebo given once per day . After the first day of treatment , the daily dose could be adjusted upward or downward , as clinical ly indicated , by one capsule ( olanzapine , 5 mg/day ) within the allowed range of one to four capsules . The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale . Clinical response was defined a priori as a decrease of 50 % or more from baseline in Young Mania Rating Scale total score . RESULTS The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group . On the basis of the clinical response criteria , significantly more olanzapine-treated patients ( 48.6 % ) responded than those assigned to placebo ( 24.2 % ) . Somnolence , dizziness , dry mouth , and weight gain occurred significantly more often with olanzapine . There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism , akathisia , and dyskinesias . No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group . CONCLUSIONS The results from this study suggest that compared with placebo , olanzapine has superior efficacy for the symptoms of acute mania 
    Output:
    