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: Antidepressant effects and unintended effects of paroxetine ( 30 mg/day ) and clomipramine ( 150 mg/day ) were compared in a double-blind , r and omized , inpatient , fixed-dose , plasma-level-controlled study . Patients with a DSM-III diagnosis of major depressive disorder participated . After 1 week of single-blind placebo treatment  120 patients fulfilled the criterion of a Hamilton ( 17-item ) score of greater than or equal to 18 and were started on active treatment for 6 weeks . Drop-outs on paroxetine ( n = 12 ) were largely due to lack of effect , and on clomipramine ( n = 19 ) due to lack of effect ( n = 7 ) , adverse reactions or severe side effects ( n = 10 ) and development of mania ( n = 2 ) . According to the protocol , non-responders ( Hamilton total greater than or equal to 16 ) after 4 weeks active treatment were terminated , and this occurred to 23 patients on paroxetine and four patients on clomipramine . Categorical response measures and group averages of rating scores showed a significantly better therapeutic effect of clomipramine from the second week of treatment on . These results are very similar to our earlier results with another selective serotonin reuptake inhibitor ( citalopram ) , but generally at variance with the literature on this class of antidepressants , which , however , mostly deals with outpatient studies This 8-week , r and omised , double-blind study compared the efficacy and tolerability of escitalopram to that of venlafaxine XR in primary care patients with major depressive disorder . The efficacy of escitalopram ( 10– 20 mg ; n = 148 ) was similar to venlafaxine XR ( 75– 150 mg ; n = 145 ) , based on mean change from baseline to week 8 in Montgomery and Åsberg Depression Rating Scale total score . In ad hoc analyses , escitalopram-treated patients achieved sustained remission significantly faster than did venlafaxine-treated patients . More venlafaxine-treated patients had nausea , constipation , and increased sweating ( p < 0.05 ) . When treatment was completed after 8 weeks , significantly more venlafaxine-treated patients had discontinuation symptoms ( p < 0.01 ) . Thus escitalopram treatment was similar to venlafaxine treatment with respect to efficacy and was better tolerated by patients in primary care ABSTRACT Objective : This study evaluated the efficacy and tolerability of escitalopram and duloxetine in the treatment of major depressive disorder ( MDD ) . Research design and methods : Patients were r and omised to 24 weeks of double-blind treatment with fixed doses of escitalopram ( 20 mg ) ( n = 143 ) or duloxetine ( 60 mg ) ( n = 151 ) . The primary analysis of efficacy was an analysis of covariance ( ANCOVA ) of change from baseline to endpoint ( week 24 ) in MADRS total score ( last observation carried forward ) . Main outcome measures ; Results : At week 8 , the mean change from baseline in total MADRS score was –19.5 for patients treated with escitalopram ( n = 141 ) and –17.4 for patients treated with duloxetine ( n = 146 ) , a difference of 2.1 points ( p < 0.05 ) . At week 8 , the proportion of responders ( ≥ 50 % decrease in MADRS ) was 69 % ( escitalopram ) and 58 % ( duloxetine ) ( p < 0.05 ) and remission ( MADRS ≤ 12 ) rates were 56 % ( escitalopram ) and 48 % ( duloxetine ) ( NS ) . For the primary endpoint , the mean change from baseline in total MADRS score at week 24 was –23.4 for patients treated with escitalopram and –21.7 for patients treated with duloxetine , a difference of 1.7 points ( p = 0.055 , one-sided ) . The difference in mean change from baseline in MADRS total score favoured escitalopram at weeks 1 , 2 , 4 , 8 , 12 and 16 ( p < 0.05 ) . The overall withdrawal rates were 22 % ( escitalopram ) and 25 % ( duloxetine ) ( NS ) . The withdrawal rate due to adverse events was lower for escitalopram ( 9 % ) compared to duloxetine ( 17 % ) ( p < 0.05 ) and significantly more patients treated with duloxetine reported insomnia ( 12.6 % vs. 4.9 % ) and constipation ( 8.6 % vs. 2.8 % ) . Conclusion : Escitalopram was superior to duloxetine in acute treatment and at least as efficacious and better tolerated in long-term treatment of MDD Objective : To test the hypothesis that in patients with major depressive disorder ( MDD ) , the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors ( SSRIs ) and that patterns of response will differ based on symptom severity at baseline . Method : Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD : 7 r and omized , double-blind , fixed-dose , 8-week studies of duloxetine  ( n = 1,133 )  versus SSRI  ( n = 689 )  versus placebo  ( n = 641 ) .  Duloxetine doses were 40 , 60 , 80 and 120 mg/day . SSRI doses were 10 mg/day ( escitalopram ) and 20 mg/day ( fluoxetine and paroxetine ) . Results : Compared to SSRI-treated patients , duloxetine-treated patients had a significantly greater ( p ≤ 0.05 ) reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score and HAMD17 items of work and activities , psychomotor retardation , genital symptoms and hypochondriasis . Differences favoring the SSRIs approached significance for middle insomnia ( p = 0.057 ) and late insomnia ( p = 0.06 ) , with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine . Similarly , the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms ( p = 0.056 ) , with an effect size twice that observed for the SSRIs . The HAMD17 total score difference was driven mostly by patients with lower baseline MDD severity ( HAMD17 total score ≤19 ) , where the HAMD17 effect size advantage for duloxetine over combined SSRIs was statistically significant ( p = 0.031 ) . Conclusion : Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity , and different HAMD17 items responded differently to duloxetine compared with SSRIs . Underst and ing these differences may be useful in tailoring antidepressant therapy for individual patients OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results In recent years , the use of the last observation carried forward ( LOCF ) approach in imputing missing data in clinical trials has been greatly criticized , and several likelihood-based modeling approaches are proposed to analyze such incomplete data . One of the proposed likelihood-based methods is the Mixed-Effect Model Repeated Measure ( MMRM ) model . To compare the performance of LOCF and MMRM approaches in analyzing incomplete data , two extensive simulation studies are conducted , and the empirical bias and Type I error rates associated with estimators and tests of treatment effects under three missing data paradigms are evaluated . The simulation studies demonstrate that LOCF analysis can lead to substantial biases in estimators of treatment effects and can greatly inflate Type I error rates of the statistical tests , whereas MMRM analysis on the available data leads to estimators with comparatively small bias , and controls Type I error rates at a nominal level in the presence of missing completely at r and om ( MCAR ) or missing at r and om ( MAR ) and some possibility of missing not at r and om ( MNAR ) data . In a sensitivity analysis of 48 clinical trial data sets obtained from 25 New Drug Applications ( NDA ) su bmi ssions of neurological and psychiatric drug products , MMRM analysis appears to be a superior approach in controlling Type I error rates and minimizing biases , as compared to LOCF ANCOVA analysis . In the exploratory analyses of the data sets , no clear evidence of the presence of MNAR missingness is found BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor ( SSRI ) , it is not known whether switching to one antidepressant is more effective than switching to another . METHODS We r and omly assigned 727 adult out patients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram  to receive one of the following drugs for up to 14 weeks : sustained-release bupropion ( 239 patients ) at a maximal daily dose of 400 mg , sertraline ( 238 patients ) at a maximal daily dose of 200 mg , or extended-release venlafaxine ( 250 patients ) at a maximal daily dose of 375 mg . The study was conducted in 18 primary and 23 psychiatric care setting s. The primary outcome was symptom remission , defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of the study . Scores on the Quick Inventory of Depressive Symptomatology - Self Report ( QIDS-SR-16 ) , obtained at treatment visits , determined secondary outcomes , including remission ( a score of 5 or less at exit ) and response ( a reduction of 50 percent or more on baseline scores ) . RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16 , respectively , were 21.3 percent and 25.5 percent for sustained-release bupropion , 17.6 percent and 26.6 percent for sertraline , and 24.8 percent and 25.0 percent for extended-release venlafaxine . QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion , 26.7 percent for sertraline , and 28.2 percent for extended-release venlafaxine . These treatments did not differ significantly with respect to outcomes , tolerability , or adverse events . CONCLUSIONS After unsuccessful treatment with an SSRI , approximately one in four patients had a remission of symptoms after switching to another antidepressant . Any one of the medications in the study provided a reasonable second-step choice for patients with depression . ( Clinical Trials.gov number , NCT00021528 . ) BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day 
    Output:
    
agent
Evidence from meta- analysis of r and omised controlled trials ( RCTs ) and r and omised pragmatic trials was found in support of greater efficacy of the serotonin noradrenaline reuptake inhibitors ( SNRIs ) , venlafaxine and duloxetine , in moderate to severe depression compared to SSRIs but no evidence was found for superiority of milnacipran .
There is sufficient current evidence that demonstrates an increase in efficacy , when noradrenaline reuptake is added to serotonin ( 5-HT ) reuptake , to suggest that patients with severe depression or those who have failed to reach remission with a SSRI may benefit from treatment with a SNRI .
***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: Antidepressant effects and unintended effects of paroxetine ( 30 mg/day ) and clomipramine ( 150 mg/day ) were compared in a double-blind , r and omized , inpatient , fixed-dose , plasma-level-controlled study . Patients with a DSM-III diagnosis of major depressive disorder participated . After 1 week of single-blind placebo treatment  120 patients fulfilled the criterion of a Hamilton ( 17-item ) score of greater than or equal to 18 and were started on active treatment for 6 weeks . Drop-outs on paroxetine ( n = 12 ) were largely due to lack of effect , and on clomipramine ( n = 19 ) due to lack of effect ( n = 7 ) , adverse reactions or severe side effects ( n = 10 ) and development of mania ( n = 2 ) . According to the protocol , non-responders ( Hamilton total greater than or equal to 16 ) after 4 weeks active treatment were terminated , and this occurred to 23 patients on paroxetine and four patients on clomipramine . Categorical response measures and group averages of rating scores showed a significantly better therapeutic effect of clomipramine from the second week of treatment on . These results are very similar to our earlier results with another selective serotonin reuptake inhibitor ( citalopram ) , but generally at variance with the literature on this class of antidepressants , which , however , mostly deals with outpatient studies This 8-week , r and omised , double-blind study compared the efficacy and tolerability of escitalopram to that of venlafaxine XR in primary care patients with major depressive disorder . The efficacy of escitalopram ( 10– 20 mg ; n = 148 ) was similar to venlafaxine XR ( 75– 150 mg ; n = 145 ) , based on mean change from baseline to week 8 in Montgomery and Åsberg Depression Rating Scale total score . In ad hoc analyses , escitalopram-treated patients achieved sustained remission significantly faster than did venlafaxine-treated patients . More venlafaxine-treated patients had nausea , constipation , and increased sweating ( p < 0.05 ) . When treatment was completed after 8 weeks , significantly more venlafaxine-treated patients had discontinuation symptoms ( p < 0.01 ) . Thus escitalopram treatment was similar to venlafaxine treatment with respect to efficacy and was better tolerated by patients in primary care ABSTRACT Objective : This study evaluated the efficacy and tolerability of escitalopram and duloxetine in the treatment of major depressive disorder ( MDD ) . Research design and methods : Patients were r and omised to 24 weeks of double-blind treatment with fixed doses of escitalopram ( 20 mg ) ( n = 143 ) or duloxetine ( 60 mg ) ( n = 151 ) . The primary analysis of efficacy was an analysis of covariance ( ANCOVA ) of change from baseline to endpoint ( week 24 ) in MADRS total score ( last observation carried forward ) . Main outcome measures ; Results : At week 8 , the mean change from baseline in total MADRS score was –19.5 for patients treated with escitalopram ( n = 141 ) and –17.4 for patients treated with duloxetine ( n = 146 ) , a difference of 2.1 points ( p < 0.05 ) . At week 8 , the proportion of responders ( ≥ 50 % decrease in MADRS ) was 69 % ( escitalopram ) and 58 % ( duloxetine ) ( p < 0.05 ) and remission ( MADRS ≤ 12 ) rates were 56 % ( escitalopram ) and 48 % ( duloxetine ) ( NS ) . For the primary endpoint , the mean change from baseline in total MADRS score at week 24 was –23.4 for patients treated with escitalopram and –21.7 for patients treated with duloxetine , a difference of 1.7 points ( p = 0.055 , one-sided ) . The difference in mean change from baseline in MADRS total score favoured escitalopram at weeks 1 , 2 , 4 , 8 , 12 and 16 ( p < 0.05 ) . The overall withdrawal rates were 22 % ( escitalopram ) and 25 % ( duloxetine ) ( NS ) . The withdrawal rate due to adverse events was lower for escitalopram ( 9 % ) compared to duloxetine ( 17 % ) ( p < 0.05 ) and significantly more patients treated with duloxetine reported insomnia ( 12.6 % vs. 4.9 % ) and constipation ( 8.6 % vs. 2.8 % ) . Conclusion : Escitalopram was superior to duloxetine in acute treatment and at least as efficacious and better tolerated in long-term treatment of MDD Objective : To test the hypothesis that in patients with major depressive disorder ( MDD ) , the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors ( SSRIs ) and that patterns of response will differ based on symptom severity at baseline . Method : Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD : 7 r and omized , double-blind , fixed-dose , 8-week studies of duloxetine  ( n = 1,133 )  versus SSRI  ( n = 689 )  versus placebo  ( n = 641 ) .  Duloxetine doses were 40 , 60 , 80 and 120 mg/day . SSRI doses were 10 mg/day ( escitalopram ) and 20 mg/day ( fluoxetine and paroxetine ) . Results : Compared to SSRI-treated patients , duloxetine-treated patients had a significantly greater ( p ≤ 0.05 ) reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score and HAMD17 items of work and activities , psychomotor retardation , genital symptoms and hypochondriasis . Differences favoring the SSRIs approached significance for middle insomnia ( p = 0.057 ) and late insomnia ( p = 0.06 ) , with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine . Similarly , the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms ( p = 0.056 ) , with an effect size twice that observed for the SSRIs . The HAMD17 total score difference was driven mostly by patients with lower baseline MDD severity ( HAMD17 total score ≤19 ) , where the HAMD17 effect size advantage for duloxetine over combined SSRIs was statistically significant ( p = 0.031 ) . Conclusion : Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity , and different HAMD17 items responded differently to duloxetine compared with SSRIs . Underst and ing these differences may be useful in tailoring antidepressant therapy for individual patients OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results In recent years , the use of the last observation carried forward ( LOCF ) approach in imputing missing data in clinical trials has been greatly criticized , and several likelihood-based modeling approaches are proposed to analyze such incomplete data . One of the proposed likelihood-based methods is the Mixed-Effect Model Repeated Measure ( MMRM ) model . To compare the performance of LOCF and MMRM approaches in analyzing incomplete data , two extensive simulation studies are conducted , and the empirical bias and Type I error rates associated with estimators and tests of treatment effects under three missing data paradigms are evaluated . The simulation studies demonstrate that LOCF analysis can lead to substantial biases in estimators of treatment effects and can greatly inflate Type I error rates of the statistical tests , whereas MMRM analysis on the available data leads to estimators with comparatively small bias , and controls Type I error rates at a nominal level in the presence of missing completely at r and om ( MCAR ) or missing at r and om ( MAR ) and some possibility of missing not at r and om ( MNAR ) data . In a sensitivity analysis of 48 clinical trial data sets obtained from 25 New Drug Applications ( NDA ) su bmi ssions of neurological and psychiatric drug products , MMRM analysis appears to be a superior approach in controlling Type I error rates and minimizing biases , as compared to LOCF ANCOVA analysis . In the exploratory analyses of the data sets , no clear evidence of the presence of MNAR missingness is found BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor ( SSRI ) , it is not known whether switching to one antidepressant is more effective than switching to another . METHODS We r and omly assigned 727 adult out patients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram  to receive one of the following drugs for up to 14 weeks : sustained-release bupropion ( 239 patients ) at a maximal daily dose of 400 mg , sertraline ( 238 patients ) at a maximal daily dose of 200 mg , or extended-release venlafaxine ( 250 patients ) at a maximal daily dose of 375 mg . The study was conducted in 18 primary and 23 psychiatric care setting s. The primary outcome was symptom remission , defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of the study . Scores on the Quick Inventory of Depressive Symptomatology - Self Report ( QIDS-SR-16 ) , obtained at treatment visits , determined secondary outcomes , including remission ( a score of 5 or less at exit ) and response ( a reduction of 50 percent or more on baseline scores ) . RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16 , respectively , were 21.3 percent and 25.5 percent for sustained-release bupropion , 17.6 percent and 26.6 percent for sertraline , and 24.8 percent and 25.0 percent for extended-release venlafaxine . QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion , 26.7 percent for sertraline , and 28.2 percent for extended-release venlafaxine . These treatments did not differ significantly with respect to outcomes , tolerability , or adverse events . CONCLUSIONS After unsuccessful treatment with an SSRI , approximately one in four patients had a remission of symptoms after switching to another antidepressant . Any one of the medications in the study provided a reasonable second-step choice for patients with depression . ( Clinical Trials.gov number , NCT00021528 . ) BACKGROUND The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75 - 150 mg/day with that of citalopram 10 - 20 mg/day 
    Output:
    