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: This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy These data provide evidence for the antidepressant efficacy of paroxetine . Paroxetine- and imipramine-treated patients were significantly different from  placebo-treated patients , but little different to each other , on all depressive outcome measures . However , paroxetine appeared to have a possibly greater and earlier beneficial effect on anxiety symptoms associated with depression , when compared with imipramine . Both active therapies were effective in treating patients with severe depression . Side effects for paroxetine were typical of other serotonin ( 5-HT ) uptake inhibitors but different from those of imipramine . In particular , anticholinergic and cardiovascular symptoms were reduced , and premature withdrawal less likely BACKGROUND Citalopram is a racemic selective serotonin reuptake inhibitor ( SSRI ) indicated for the treatment of depression . Citalopram is a racemate and its serotonin reuptake inhibitory activity resides primarily in the single S-isomer , escitalopram , which is now being evaluated for its potential usefulness in the treatment of depression and other psychiatric disorders . RESULTS from placebo-controlled studies that also included citalopram as an active control have shown that escitalopram is effective in treating depression and associated symptoms of anxiety . However , none of these studies was powered sufficiently to detect differences between active treatment groups . The goal of the present analysis is to evaluate the efficacy of escitalopram compared with citalopram in the treatment of major depressive disorder . METHOD Data were pooled from three similarly design ed , r and omized , double-blind , placebo-controlled trials of escitalopram ( 10 - 20 mg/day ) and citalopram ( 20 - 40 mg/day ) . Patients were male or female , greater than or equal to 18 years of age , who met criteria for a major depressive episode with a Montgomery Asberg Depression Rating Scale ( MADRS ) score greater than or equal to 22 at baseline . Efficacy measures included change from baseline in MADRS score and the Clinical Global Impression of Improvement ( CGI-I ) scale . Improvement in associated symptoms of anxiety was measured using the change from baseline in the MADRS inner tension item . RESULTS Both escitalopram and citalopram significantly improved depression and anxiety symptoms compared with placebo , and there were significantly more MADRS responders ( defined as > /=50 % improvement in MADRS scores at end point ) in the escitalopram and citalopram treatment groups . Escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment , whereas citalopram treatment statistically separated from placebo at the end of week 4 ( CGI-I and MADRS inner tension ) or week 6 ( MADRS ) . Escitalopram treatment also was statistically significantly superior to citalopram treatment at a number of time points . CONCLUSION These data support the effectiveness of escitalopram and citalopram in the treatment of major depressive disorder , and suggest escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day  ( n = 191 ) or placebo  ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated The clinical profile of reboxetine , a selective noradrenaline reuptake inhibitor , was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind , multicenter , parallel-group clinical trial of patients with major depression . Among the 381 patients treated with reboxetine 8 to 10 mg/day , fluoxetine 20 to 40 mg/day , or placebo for up to 8 weeks , a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression ( 21-item HAM-D ) total score ( the primary efficacy variable ) was seen for both active treatment groups compared with placebo ( p < 0.024 ) . A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response ( ≥50 % reduction in HAM-D ) or remission ( HAM-D ≤10 points ) than those who received placebo ( p < 0.01 for both analyses ) . Similar findings were recorded in a sub population of severely ill patients , with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo ( p < 0.024 ) . Additional efficacy assessment s ( Montgomery-Åsberg Depression Rating Scale , Clinical Global Impression ) reflected the primary efficacy analysis , with both active treatments offering comparable efficacy that was superior to that of placebo . Reboxetine and fluoxetine are more effective  than placebo in the treatment of major depression . Futhermore , both antidepressants are well tolerated but possess different adverse event profiles As part of a study in which reduced rapid eye movement latency was used to predict treatment response , fluoxetine and placebo were compared in 89 out patients with major depression with ( n = 52 ) and without ( n = 37 ) DSM-III-R melancholia , to determine whether the presence or absence of melancholia predicted antidepressant and /or placebo response . Following a 2-week , single blind placebo lead-in , men and women were assigned by r and om allocation to double-blind fluoxetine , 20 mg/day , or placebo for 8 weeks . Fluoxetine was statistically significantly superior to placebo in patients with melancholia  ( endpoint change in the Montgomery-åsberg Depression Rating Scale [ MADRS ] score , response rates and remission rates ) . A weekly analysis demonstrated statistical superiority of fluoxetine compared with placebo at week 3 and continuing for the remainder of the study . Fluoxetine was statistically significantly more likely to reduce suicidal ideation compared with placebo , using the MADRS item 10 ( suicidal ideation question ) CONTEXT Paroxetine controlled release ( CR ) is approved for the treatment of major depressive disorder ( MDD ) in the dosage range of 25 to 62.5 mg daily . However , lower daily doses ( 12.5 mg and 25 mg ) of this formulation have not been investigated in the treatment of MDD . If the 12.5-mg and 25-mg doses are found to be efficacious , these lower doses may well convey a superior tolerability profile for paroxetine CR in the treatment of MDD . OBJECTIVE To evaluate the antidepressant efficacy and tolerability profile of daily doses of paroxetine CR 12.5 mg and 25 mg versus placebo in the treatment of MDD . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 40 clinical investigation centers in the United States . PARTICIPANTS 44 
    Output:
    
agent
Treatment with SSRIs rather than placebo was associated with clinical improvement by the end of the first week of use .
CONCLUSIONS Treatment with SSRIs is associated with symptomatic improvement in depression by the end of the first week of use , and the improvement continues at a decreasing rate for at least 6 weeks
***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: This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy These data provide evidence for the antidepressant efficacy of paroxetine . Paroxetine- and imipramine-treated patients were significantly different from  placebo-treated patients , but little different to each other , on all depressive outcome measures . However , paroxetine appeared to have a possibly greater and earlier beneficial effect on anxiety symptoms associated with depression , when compared with imipramine . Both active therapies were effective in treating patients with severe depression . Side effects for paroxetine were typical of other serotonin ( 5-HT ) uptake inhibitors but different from those of imipramine . In particular , anticholinergic and cardiovascular symptoms were reduced , and premature withdrawal less likely BACKGROUND Citalopram is a racemic selective serotonin reuptake inhibitor ( SSRI ) indicated for the treatment of depression . Citalopram is a racemate and its serotonin reuptake inhibitory activity resides primarily in the single S-isomer , escitalopram , which is now being evaluated for its potential usefulness in the treatment of depression and other psychiatric disorders . RESULTS from placebo-controlled studies that also included citalopram as an active control have shown that escitalopram is effective in treating depression and associated symptoms of anxiety . However , none of these studies was powered sufficiently to detect differences between active treatment groups . The goal of the present analysis is to evaluate the efficacy of escitalopram compared with citalopram in the treatment of major depressive disorder . METHOD Data were pooled from three similarly design ed , r and omized , double-blind , placebo-controlled trials of escitalopram ( 10 - 20 mg/day ) and citalopram ( 20 - 40 mg/day ) . Patients were male or female , greater than or equal to 18 years of age , who met criteria for a major depressive episode with a Montgomery Asberg Depression Rating Scale ( MADRS ) score greater than or equal to 22 at baseline . Efficacy measures included change from baseline in MADRS score and the Clinical Global Impression of Improvement ( CGI-I ) scale . Improvement in associated symptoms of anxiety was measured using the change from baseline in the MADRS inner tension item . RESULTS Both escitalopram and citalopram significantly improved depression and anxiety symptoms compared with placebo , and there were significantly more MADRS responders ( defined as > /=50 % improvement in MADRS scores at end point ) in the escitalopram and citalopram treatment groups . Escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment , whereas citalopram treatment statistically separated from placebo at the end of week 4 ( CGI-I and MADRS inner tension ) or week 6 ( MADRS ) . Escitalopram treatment also was statistically significantly superior to citalopram treatment at a number of time points . CONCLUSION These data support the effectiveness of escitalopram and citalopram in the treatment of major depressive disorder , and suggest escitalopram may have a faster onset and greater overall magnitude of effect than citalopram in improving symptoms of depression and anxiety in patients with major depressive disorder Escitalopram , a selective serotonin reuptake inhibitor ( SSRI ) , was compared to placebo in a study of patients with major depressive disorder ( DSM-IV ) who had baseline Montgomery – Åsberg Depression Rating Scale ( MADRS ) total scores ≥22 and ≤40 . After a 1-week , single-blind placebo period , patients were r and omized to receive escitalopram 10 mg/day  ( n = 191 ) or placebo  ( n = 189 ) in an 8-week , double-blind period . The primary efficacy analysis of adjusted mean change in MADRS total score from baseline showed a statistically significantly larger effect for escitalopram than for placebo with a treatment difference at week 8 ( last observation carried forward , LOCF ) of 2.7 points ( SE 0.85;P = 0.002 ) . In further by-week efficacy analyses , the effect of escitalopram was consistently larger than that of placebo ( P < 0.05 ) beginning at week 1 ( Clinical Global Impression – Improvement score ) , week 2 ( MADRS score ) or week 3 ( Clinical Global Impression – Severity score ) . Escitalopram was very well tolerated with a low overall withdrawal rate similar to that for placebo . Nausea was the only adverse event reported significantly more in escitalopram-treated patients than in placebo-treated patients , although it was infrequent and transient . Escitalopram 10 mg/day had a statistically significantly better antidepressant effect than placebo as early as week 1 , and was safe and very well tolerated The clinical profile of reboxetine , a selective noradrenaline reuptake inhibitor , was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind , multicenter , parallel-group clinical trial of patients with major depression . Among the 381 patients treated with reboxetine 8 to 10 mg/day , fluoxetine 20 to 40 mg/day , or placebo for up to 8 weeks , a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression ( 21-item HAM-D ) total score ( the primary efficacy variable ) was seen for both active treatment groups compared with placebo ( p < 0.024 ) . A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response ( ≥50 % reduction in HAM-D ) or remission ( HAM-D ≤10 points ) than those who received placebo ( p < 0.01 for both analyses ) . Similar findings were recorded in a sub population of severely ill patients , with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo ( p < 0.024 ) . Additional efficacy assessment s ( Montgomery-Åsberg Depression Rating Scale , Clinical Global Impression ) reflected the primary efficacy analysis , with both active treatments offering comparable efficacy that was superior to that of placebo . Reboxetine and fluoxetine are more effective  than placebo in the treatment of major depression . Futhermore , both antidepressants are well tolerated but possess different adverse event profiles As part of a study in which reduced rapid eye movement latency was used to predict treatment response , fluoxetine and placebo were compared in 89 out patients with major depression with ( n = 52 ) and without ( n = 37 ) DSM-III-R melancholia , to determine whether the presence or absence of melancholia predicted antidepressant and /or placebo response . Following a 2-week , single blind placebo lead-in , men and women were assigned by r and om allocation to double-blind fluoxetine , 20 mg/day , or placebo for 8 weeks . Fluoxetine was statistically significantly superior to placebo in patients with melancholia  ( endpoint change in the Montgomery-åsberg Depression Rating Scale [ MADRS ] score , response rates and remission rates ) . A weekly analysis demonstrated statistical superiority of fluoxetine compared with placebo at week 3 and continuing for the remainder of the study . Fluoxetine was statistically significantly more likely to reduce suicidal ideation compared with placebo , using the MADRS item 10 ( suicidal ideation question ) CONTEXT Paroxetine controlled release ( CR ) is approved for the treatment of major depressive disorder ( MDD ) in the dosage range of 25 to 62.5 mg daily . However , lower daily doses ( 12.5 mg and 25 mg ) of this formulation have not been investigated in the treatment of MDD . If the 12.5-mg and 25-mg doses are found to be efficacious , these lower doses may well convey a superior tolerability profile for paroxetine CR in the treatment of MDD . OBJECTIVE To evaluate the antidepressant efficacy and tolerability profile of daily doses of paroxetine CR 12.5 mg and 25 mg versus placebo in the treatment of MDD . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 40 clinical investigation centers in the United States . PARTICIPANTS 44 
    Output:
    