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: Major Depression with Psychotic Features ( psychotic depression ) is a common , debilitating psychiatric disease . We hypothesized that mifepristone , a cortisol receptor ( GRII ) antagonist , would significantly reduce psychotic symptoms in psychotic depression . Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were r and omized to mifepristone or placebo for 7 days . The primary outcome was rapid and sustained response , defined as a 50 % or greater decrease in Brief Psychiatric Rating Scale - Positive Symptom Subscale scores at the end of treatment ( day7 ) and 49 days later ( day 56 ) . Cochran-Mantel-Haenszel compared proportions of responders to mifepristone versus placebo adjusting for site . Exploratory analyses compared response of patients with mifepristone plasma concentrations of > or = 1800 ng/ml to placebo . The primary endpoint was not statistically significant . However , the Breslow-Day test indicated a statistically significant site-by-treatment interaction . Mifepristone produced significantly higher response among the twenty sites who participated from the trial onset ( p<.05 ) , whereas no difference was observed at the nine sites added late in the trial . Patients with  mifepristone plasma levels > or = 1800 ng/ml were significantly more likely to respond than placebo patients ( Intent-to-Treat : OR=2.4 , p=.03 ; Initial 20 sites : OR=4.1 , p=.002 ) . The results of this trial are instructive in two respects . First , while statistical adjustments for [ corrected ] site are common in multisite clinical trials , this study reminds trialists to formally evaluate the interaction of site by treatment . Second , the association between increased  mifepristone plasma concentration levels and greater clinical response , detected despite the site-by-treatment interaction , suggests that higher plasma levels may be needed for maximizing the probability of a positive response Objective To compare the efficacy of imipramine and fluvoxamine in in patients from two centers suffering from a depressive disorder according to DSM IV criteria . Methods The study included 141 patients with a depressive disorder according to DSM IV criteria . After a drug-free and placebo run-in period of 1 week , patients were r and omized to imipramine or fluvoxamine ; doses of both drugs were adjusted to a predefined target blood level . Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level . Results The mean age of the study group ( 47 males , 94 females ) was 51.8 ( range 19–65 ) years . Of these 141 patients , 56 had episode duration longer than 1 year , 48 had mood congruent psychotic features , and 138 patients received medication . Seven patients did not complete the medication trial . The total number of patients using concurrent medication was 12/138 ( 8.6 % ) . On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI ( χ2 exact trend test=4.089 , df=1 , P=0.048 ) . There was no significant difference in 50 % or more reduction on the HRSD , the other primary outcome criterion . On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group ( mean difference=3.1 , st and ard error (SE)=1.4 , t=2.15 , df=136 , P=0.033 ) . There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation . Conclusions In depressed in patients imipramine is more efficacious than fluvoxamine . Both drugs were well tolerated by all patients This article reports on the evidence for the validity of psychotic major depression as a distinct subtype based on cross-sectional and 1-year prospect i ve data from the Epidemiologic Catchment Area study . Consistent with findings from previous clinical studies , only about 14 % of major depressions were accompanied by psychotic features . Psychotic as compared with nonpsychotic depression had a more severe course , as reflected in increased risk of relapse , persistence over 1 year , suicide attempts , hospitalization , comorbidity , and financial dependency . These differences could not be explained by differences in demographic characteristics or by symptom severity , as assessed by symptom profile or number of symptoms . The boundary problem with schizophrenia and bipolar affective disorder that is seen in clinical studies was also found in this sample . To our knowledge , this is the first study to examine the validity of psychotic depression in a community sample ; the findings are consistent with those from clinical sample s. They support the clinical significance of psychotic depression and the continuation of its inclusion as a distinct subtype in DSM-IV The rationale for treating psychotic major depression with glucocorticoid receptor ( GR ) antagonists is review ed . Five patients with psychotic major depression were given 600 mg of mifepristone in a 4-day , double-blind , placebo-controlled crossover study . All the patients completed the protocol and adverse effects were not observed or reported . All of the five patients showed substantial improvements in their Hamilton Rating Scale for Depression scores while they were receiving mifepristone , and four of the five patients showed substantial improvement in their Brief Psychiatric Rating Scale scores . Little , if any , improvement was seen with placebo . These preliminary results suggest that short-term use of GR antagonists may be effective in the treatment of psychotic major depression and that additional study , perhaps using higher doses or more treatment days , seems warranted Patients with psychotic depression respond well when treated with a combination of an antidepressant and antipsychotic medication . We previously reported that they will respond in a similar fashion when treated with amoxapine monotherapy . There are few prospect i ve studies on the pharmacologic treatment response of psychotic depression subtypes . We treated 37 in patients , 21 with mood congruent ( MC ) psychotic depression and 16 with mood incongruent ( MI ) psychotic depression , in a r and omized double-blind fashion with either the combination of amitriptyline and perphenazine or with amoxapine for 4 weeks . Depression and psychosis ratings improved in a similar manner in both the MC or MI patients irrespective of medication treatment group . Global response rates were similar in the MI patients and MC patients . The data suggest that classifying psychotic depression into MC versus MI subtypes may have limited acute prognostic value in pharmacotherapy response rates High rates of attrition have been reported in r and omized controlled trials of patients with severe psychiatric illness , including psychotic depression ( MDpsy ) . The purpose of this study is to examine factors associated with overall attrition and with subtypes of attrition in the Study of the Pharmacotherapy of Psychotic Depression ( STOP-PD ) . Secondary analysis of data collected in a multi-site , r and omized , placebo-controlled trial . Clinical services of academic hospitals . Participants comprised 259 persons with MDpsy , aged 18 - 93 years . The intervention consisted of the r and om allocation to 12 weeks of treatment of either olanzapine plus sertraline or olanzapine plus placebo . Demographic and clinical variables associated with overall non-completion and sub-types of non-completion of r and omized treatment . One hundred and seventeen ( 45.2 % ) subjects did not complete 12 weeks of r and omized treatment . In a logistic regression analysis , inpatient entry status , olanzapine monotherapy , and higher cumulative medical burden were statistically significant independent predictors of overall non-completion . In a multinomial logistic regression model that examined predictors of subtypes of non-completion , subjects who entered the study as an inpatient were less likely to complete because of inadequate efficacy as determined by the investigator , and older subjects were less likely to complete because of poorer tolerability . Subjects who were assigned to olanzapine monotherapy , younger subjects , and subjects who entered the study as in patients were less likely to complete because of reasons other than efficacy or tolerability . Underst and ing factors that contribute to premature discontinuation in studies of MDpsy , and to the specific reasons for attrition , has the potential to improve the management of this disorder , as well as improve the design of future clinical trials of MDpsy Abstract : This prospect i ve study assessed the influence of resistance to antidepressant pharmacotherapy on the short-term response to subsequent electroconvulsive therapy ( ECT ) . Previous research has shown that patients with medication resistance were less likely to respond to ECT . This finding may be applicable to the population of depressed in patients in The Netherl and s , where ECT is often preceded by several medication trials . Eighty-five patients ( 61 female and 24 male patients ) with DSM-IV criteria for depressive disorder , both with and without mood congruent psychotic features , were included for analysis . Medication resistance was rated with the Antidepressant Treatment History Form . Medication resistance was predefined in accordance with the previous research in this field . When a reduction of at least 50 % on the 17-item version of the Hamilton Rating Scale for Depression ( HRSD ) between pre- and post-ECT is used as response criterion , medication-resistant patients were equally likely to respond to subsequent ECT ( 30/48 = 82.5 % ) than patients without medication resistance ( 30/37 = 81.1 % ) . Even when post-ECT HRSD score ≤7 was used ( full remission ) , there was no significant difference between medication-resistant patients ( 21/48 = 43.8 % ) and patients without medication resistance ( 15/37 = 40.5 % ) . When potential confounding variables were taken into account , these differences remain nonsignificant . In contrast to earlier research , medication resistance does not influence short-term response to subsequent ECT and it can still be of considerable efficacy Psychotic major depression ( PMD ) is found to be a relatively common psychiatric condition that affects up to nearly 20 % of patients with major depression . Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone , in addition to restoring a more normal afternoon cortisol release . The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed . In total , 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a r and omized double-blind manner . The Hamilton Depression Rating Scale ( HDRS ) and the Brief Psychiatric Rating Scale ( BPRS ) were administered at baseline and again after 8 days of treatment . Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment . Significantly , more patients in the mifepristone group ( seven of 15 ) showed a 50 % or greater decline on the BPRS positive symptom subscale , an index of psychotic symptoms , as compared to the placebo group ( two of 15 ) . Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo , but these differences were not statistically significant . In addition , mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo . Clinical and biological effects of mifepristone were comparable among males and females . Age was found to significantly and positively correlate with changes in cortisol and ACTH . These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis . Additional blinded studies are warranted The authors investigated the pharmacological treatment of  delusional depression  by assigning patients on a r and om double-blind basis to amitriptyline alone , perphenazine alone , or a combination of the two . Fourteen ( 78 % ) of the 18 patients assigned to amitriptyline plus perphenazine were responders , compared with seven ( 41 % ) of 17 patients treated with amitriptyline alone and three ( 19 % ) of the 16 patients treated with perphenazine alone . The combination of amitriptyline and perphenazine was clearly superior ( p less than .01 ) Preliminary open trials performed by the authors and others with Moclobemide , a new MAO-A inhibitor , indicated that the drug has a satisfactory antidepressant activity . In the present double-blind study Moclobemide has been compared to placebo in a group of 34 unipolar psychotic or neurotic depressed patients . The mean daily dose of Moclobemide was 297 mg and treatment lasted from two to four weeks . Drug effectiveness was measured by improvements in the Hamilton Rating Scale for Depression ( HRSD ) , Clinical Global Impression ( CGI ) and 100 mm Visual Analogue Scale ( VAS ) . The results have shown that the active drug was markedly superior to placebo . The mean total score of HRSD was reduced from 41.7 to 16.5 in 18 pts . treated with Moclobemide and from 36.3 to 29.1 in 16 pts . who received placebo .  Self- assessment with VAS showed a mean reduction from 82.7 mm to 42.2 mm and from 84.3 to 70.6 mm respectively . Moderate to marked improvement was observed by the CGI in 15 cases treated with Moclobemide and mild to moderate in 5 cases who received placebo . The treatment was well tolerated Open-label studies and r and omized clinical trials have suggested that mifepristone may be effective for the treatment of major depression with psychotic features ( psychotic depression ) . A recent study reported a correlation between mifepristone plasma concentration and clinical response . The current study aim ed to evaluate the safety and 
    Output:
    
agent
Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo .
Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone
***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: Major Depression with Psychotic Features ( psychotic depression ) is a common , debilitating psychiatric disease . We hypothesized that mifepristone , a cortisol receptor ( GRII ) antagonist , would significantly reduce psychotic symptoms in psychotic depression . Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were r and omized to mifepristone or placebo for 7 days . The primary outcome was rapid and sustained response , defined as a 50 % or greater decrease in Brief Psychiatric Rating Scale - Positive Symptom Subscale scores at the end of treatment ( day7 ) and 49 days later ( day 56 ) . Cochran-Mantel-Haenszel compared proportions of responders to mifepristone versus placebo adjusting for site . Exploratory analyses compared response of patients with mifepristone plasma concentrations of > or = 1800 ng/ml to placebo . The primary endpoint was not statistically significant . However , the Breslow-Day test indicated a statistically significant site-by-treatment interaction . Mifepristone produced significantly higher response among the twenty sites who participated from the trial onset ( p<.05 ) , whereas no difference was observed at the nine sites added late in the trial . Patients with  mifepristone plasma levels > or = 1800 ng/ml were significantly more likely to respond than placebo patients ( Intent-to-Treat : OR=2.4 , p=.03 ; Initial 20 sites : OR=4.1 , p=.002 ) . The results of this trial are instructive in two respects . First , while statistical adjustments for [ corrected ] site are common in multisite clinical trials , this study reminds trialists to formally evaluate the interaction of site by treatment . Second , the association between increased  mifepristone plasma concentration levels and greater clinical response , detected despite the site-by-treatment interaction , suggests that higher plasma levels may be needed for maximizing the probability of a positive response Objective To compare the efficacy of imipramine and fluvoxamine in in patients from two centers suffering from a depressive disorder according to DSM IV criteria . Methods The study included 141 patients with a depressive disorder according to DSM IV criteria . After a drug-free and placebo run-in period of 1 week , patients were r and omized to imipramine or fluvoxamine ; doses of both drugs were adjusted to a predefined target blood level . Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level . Results The mean age of the study group ( 47 males , 94 females ) was 51.8 ( range 19–65 ) years . Of these 141 patients , 56 had episode duration longer than 1 year , 48 had mood congruent psychotic features , and 138 patients received medication . Seven patients did not complete the medication trial . The total number of patients using concurrent medication was 12/138 ( 8.6 % ) . On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI ( χ2 exact trend test=4.089 , df=1 , P=0.048 ) . There was no significant difference in 50 % or more reduction on the HRSD , the other primary outcome criterion . On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group ( mean difference=3.1 , st and ard error (SE)=1.4 , t=2.15 , df=136 , P=0.033 ) . There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation . Conclusions In depressed in patients imipramine is more efficacious than fluvoxamine . Both drugs were well tolerated by all patients This article reports on the evidence for the validity of psychotic major depression as a distinct subtype based on cross-sectional and 1-year prospect i ve data from the Epidemiologic Catchment Area study . Consistent with findings from previous clinical studies , only about 14 % of major depressions were accompanied by psychotic features . Psychotic as compared with nonpsychotic depression had a more severe course , as reflected in increased risk of relapse , persistence over 1 year , suicide attempts , hospitalization , comorbidity , and financial dependency . These differences could not be explained by differences in demographic characteristics or by symptom severity , as assessed by symptom profile or number of symptoms . The boundary problem with schizophrenia and bipolar affective disorder that is seen in clinical studies was also found in this sample . To our knowledge , this is the first study to examine the validity of psychotic depression in a community sample ; the findings are consistent with those from clinical sample s. They support the clinical significance of psychotic depression and the continuation of its inclusion as a distinct subtype in DSM-IV The rationale for treating psychotic major depression with glucocorticoid receptor ( GR ) antagonists is review ed . Five patients with psychotic major depression were given 600 mg of mifepristone in a 4-day , double-blind , placebo-controlled crossover study . All the patients completed the protocol and adverse effects were not observed or reported . All of the five patients showed substantial improvements in their Hamilton Rating Scale for Depression scores while they were receiving mifepristone , and four of the five patients showed substantial improvement in their Brief Psychiatric Rating Scale scores . Little , if any , improvement was seen with placebo . These preliminary results suggest that short-term use of GR antagonists may be effective in the treatment of psychotic major depression and that additional study , perhaps using higher doses or more treatment days , seems warranted Patients with psychotic depression respond well when treated with a combination of an antidepressant and antipsychotic medication . We previously reported that they will respond in a similar fashion when treated with amoxapine monotherapy . There are few prospect i ve studies on the pharmacologic treatment response of psychotic depression subtypes . We treated 37 in patients , 21 with mood congruent ( MC ) psychotic depression and 16 with mood incongruent ( MI ) psychotic depression , in a r and omized double-blind fashion with either the combination of amitriptyline and perphenazine or with amoxapine for 4 weeks . Depression and psychosis ratings improved in a similar manner in both the MC or MI patients irrespective of medication treatment group . Global response rates were similar in the MI patients and MC patients . The data suggest that classifying psychotic depression into MC versus MI subtypes may have limited acute prognostic value in pharmacotherapy response rates High rates of attrition have been reported in r and omized controlled trials of patients with severe psychiatric illness , including psychotic depression ( MDpsy ) . The purpose of this study is to examine factors associated with overall attrition and with subtypes of attrition in the Study of the Pharmacotherapy of Psychotic Depression ( STOP-PD ) . Secondary analysis of data collected in a multi-site , r and omized , placebo-controlled trial . Clinical services of academic hospitals . Participants comprised 259 persons with MDpsy , aged 18 - 93 years . The intervention consisted of the r and om allocation to 12 weeks of treatment of either olanzapine plus sertraline or olanzapine plus placebo . Demographic and clinical variables associated with overall non-completion and sub-types of non-completion of r and omized treatment . One hundred and seventeen ( 45.2 % ) subjects did not complete 12 weeks of r and omized treatment . In a logistic regression analysis , inpatient entry status , olanzapine monotherapy , and higher cumulative medical burden were statistically significant independent predictors of overall non-completion . In a multinomial logistic regression model that examined predictors of subtypes of non-completion , subjects who entered the study as an inpatient were less likely to complete because of inadequate efficacy as determined by the investigator , and older subjects were less likely to complete because of poorer tolerability . Subjects who were assigned to olanzapine monotherapy , younger subjects , and subjects who entered the study as in patients were less likely to complete because of reasons other than efficacy or tolerability . Underst and ing factors that contribute to premature discontinuation in studies of MDpsy , and to the specific reasons for attrition , has the potential to improve the management of this disorder , as well as improve the design of future clinical trials of MDpsy Abstract : This prospect i ve study assessed the influence of resistance to antidepressant pharmacotherapy on the short-term response to subsequent electroconvulsive therapy ( ECT ) . Previous research has shown that patients with medication resistance were less likely to respond to ECT . This finding may be applicable to the population of depressed in patients in The Netherl and s , where ECT is often preceded by several medication trials . Eighty-five patients ( 61 female and 24 male patients ) with DSM-IV criteria for depressive disorder , both with and without mood congruent psychotic features , were included for analysis . Medication resistance was rated with the Antidepressant Treatment History Form . Medication resistance was predefined in accordance with the previous research in this field . When a reduction of at least 50 % on the 17-item version of the Hamilton Rating Scale for Depression ( HRSD ) between pre- and post-ECT is used as response criterion , medication-resistant patients were equally likely to respond to subsequent ECT ( 30/48 = 82.5 % ) than patients without medication resistance ( 30/37 = 81.1 % ) . Even when post-ECT HRSD score ≤7 was used ( full remission ) , there was no significant difference between medication-resistant patients ( 21/48 = 43.8 % ) and patients without medication resistance ( 15/37 = 40.5 % ) . When potential confounding variables were taken into account , these differences remain nonsignificant . In contrast to earlier research , medication resistance does not influence short-term response to subsequent ECT and it can still be of considerable efficacy Psychotic major depression ( PMD ) is found to be a relatively common psychiatric condition that affects up to nearly 20 % of patients with major depression . Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone , in addition to restoring a more normal afternoon cortisol release . The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed . In total , 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a r and omized double-blind manner . The Hamilton Depression Rating Scale ( HDRS ) and the Brief Psychiatric Rating Scale ( BPRS ) were administered at baseline and again after 8 days of treatment . Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment . Significantly , more patients in the mifepristone group ( seven of 15 ) showed a 50 % or greater decline on the BPRS positive symptom subscale , an index of psychotic symptoms , as compared to the placebo group ( two of 15 ) . Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo , but these differences were not statistically significant . In addition , mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo . Clinical and biological effects of mifepristone were comparable among males and females . Age was found to significantly and positively correlate with changes in cortisol and ACTH . These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis . Additional blinded studies are warranted The authors investigated the pharmacological treatment of  delusional depression  by assigning patients on a r and om double-blind basis to amitriptyline alone , perphenazine alone , or a combination of the two . Fourteen ( 78 % ) of the 18 patients assigned to amitriptyline plus perphenazine were responders , compared with seven ( 41 % ) of 17 patients treated with amitriptyline alone and three ( 19 % ) of the 16 patients treated with perphenazine alone . The combination of amitriptyline and perphenazine was clearly superior ( p less than .01 ) Preliminary open trials performed by the authors and others with Moclobemide , a new MAO-A inhibitor , indicated that the drug has a satisfactory antidepressant activity . In the present double-blind study Moclobemide has been compared to placebo in a group of 34 unipolar psychotic or neurotic depressed patients . The mean daily dose of Moclobemide was 297 mg and treatment lasted from two to four weeks . Drug effectiveness was measured by improvements in the Hamilton Rating Scale for Depression ( HRSD ) , Clinical Global Impression ( CGI ) and 100 mm Visual Analogue Scale ( VAS ) . The results have shown that the active drug was markedly superior to placebo . The mean total score of HRSD was reduced from 41.7 to 16.5 in 18 pts . treated with Moclobemide and from 36.3 to 29.1 in 16 pts . who received placebo .  Self- assessment with VAS showed a mean reduction from 82.7 mm to 42.2 mm and from 84.3 to 70.6 mm respectively . Moderate to marked improvement was observed by the CGI in 15 cases treated with Moclobemide and mild to moderate in 5 cases who received placebo . The treatment was well tolerated Open-label studies and r and omized clinical trials have suggested that mifepristone may be effective for the treatment of major depression with psychotic features ( psychotic depression ) . A recent study reported a correlation between mifepristone plasma concentration and clinical response . The current study aim ed to evaluate the safety and 
    Output:
    