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 This analysis assessed the incidence , severity , onset , and duration of nausea among patients with major depressive disorder ( MDD ) treated with the new antidepressant duloxetine .  METHODS Data were pooled from 8 double-blind , r and omized , placebo- and active comparator-controlled trials employing patients with MDD that were su bmi tted to the US Food and Drug Administration to support duloxetine 's new drug application for treatment of MDD . RESULTS The numbers of patients receiving each regimen were as follows : placebo , n = 777 ;  duloxetine 40 mg/d , n = 177 ; duloxetine 60 mg/d , n = 251 ; duloxetine 80 mg/d , n = 363 ; duloxetine 120 mg/d , n = 348 ; paroxetine 20 mg/d , n = 359 ; and fluoxetine 20 mg/d , n = 70 . In acute placebo-controlled trials of duloxetine 40 to 120 mg/d , treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo ( 19.9 % [ 227/1139 ] vs 6.9 % [ 154/777 ] , respectively ; P < 0.001 ) . Among duloxetine-treated patients , the median time to onset of nausea was 1 day , and the median duration of nausea was 7 days . The incidence of nausea was similar to placebo rates after 1 week . In paroxetine-controlled studies , the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine ( 14.4 % vs 12.0 % , respectively ) . In head-to-head studies , the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine ( 17.1 % vs 15.7 % , respectively ) . Most duloxetine-treated patients reported nausea to be mild ( 52.9 % ) or moderate ( 41.4 % ) . Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo ( 1.4 % [ 16/1139 ] vs 0.1 % [ 1/777 ] , respectively ; P = 0.002 ) . Following abrupt discontinuation after acute treatment , 5.9 % of duloxetine-treated patients exhibited nausea compared with 0.3 % of patients receiving placebo ( P < 0.001 ) . The incidence of treatment-emergent nausea during 6-month continuation of duloxetine treatment ( 80 mg/d , 2.1 % ; 120 mg/d , 1.3 % ) was similar to placebo ( 1.6 % ) . Following abrupt discontinuation after 8 months of treatment , nausea was reported by 1.6 % of patients receiving duloxetine 120 mg/d compared with 0 % for those receiving duloxetine 80 mg/d and 0 % for placebo . CONCLUSIONS Duloxetine induced mild to moderate nausea in a subset of patients with MDD during treatment initiation . Nausea resolved rapidly with continued treatment . The incidence of duloxetine-induced nausea resembled that produced by paroxetine and fluoxetine Pramipexole , a dopamine D2 receptor agonist , was tested in 174 patients with major depression , with or without melancholia and without psychotic features . Three daily dose levels ( 0.375 mg , 1.0 mg , and 5.0 mg ) were compared to fluoxetine ( Prozac ) at 20 mg and placebo in a r and omized , double-blind , parallel-group study . After a 1 week placebo run-in period , patients were treated for 8 weeks , had a post- study follow-up ( week 9 ) , and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinician 's Global Impressions-Severity of Illness scale ( CGI-SI ) .  All patients who received one dose of study medication were included in the observed-case analysis ( no missing data were replaced ) . Results indicated that by endpoint ( week 8) , patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D , MADRS , and CGI-SI . Significant improvement in this dose group was seen at other timepoints as well . The most obvious improvement was seen in the pramipexole 5.0 mg group , although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study . Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study . Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day Fluoxetine , a selective serotonin reuptake inhibitor , was compared with mianserin and placebo in a double‐blind study . In total , 81 depressed patients were included . Patients were rated weekly on the Hamilton Depression Rating Scale ( HDRS ) and the Montgomery & Asberg Depression Rating Scale ( MADRS ) . The duration was 6 weeks , and 52 patients completed the study . Significantly more patients on fluoxetine improved than patients on placebo . For mianserin no significant differences were found with either fluoxetine or placebo . Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine , but not for mianserin , than placebo . Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3 . Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7 . Fluoxetine  induced weight loss , while patients on mianserin gained weight . Side effects were present in most patients on the two active drugs ; those on fluoxetine experienced nausea and vomiting , and those on mianserin drowsiness BACKGROUND We compared the efficacy and tolerability of venlafaxine XR with that of fluoxetine in a multicenter , r and omized , double-blind , placebo-controlled study in depressed out patients . METHODS Out patients , 18 years and older , who met DSM-IV criteria for major depressive disorder were included ( n = 301 r and omized ; 232 completed ) . Patients were r and omly assigned to eight weeks of treatment with either venlafaxine XR 75 - 225 mg/day ( n = 100 ) , fluoxetine 20 - 60 mg/day ( n = 103 ) , or placebo ( n = 98 ) . The primary efficacy outcome measures were the final ratings on the Hamilton Rating Scale for Depression ( HAM-D21 ) total score , HAM-D21 depressed mood item , Montgomery-Asberg Depression Rating Scale total score , and Clinical Global Impressions Scale . RESULTS Withdrawal from the study due to adverse events occurred in 6 % of the patients in the venlafaxine XR group and 9 % of the patients in the fluoxetine group . Patients treated with venlafaxine XR , but only rarely those treated with fluoxetine , had statistically significant improvements in their depression ratings compared with placebo at the end of the study . The percentages of patients who achieved full remission of their depression ( HAM-D21 total score < or = 7 ) at the end of treatment were 37 % , 22 % and 18 % for the venlafaxine XR , fluoxetine and placebo groups , respectively . The differences in remission rates between venlafaxine XR and the other groups were statistically significant ( p < 0.05 ) . LIMITATIONS The superior remission outcome observed with venlafaxine XR treatment needs to be replicated in additional studies . CONCLUSION Venlafaxine XR is a well-tolerated and efficacious treatment for depression . The results of this study suggest that venlafaxine XR is as well-tolerated as fluoxetine but may have some efficacy advantages over fluoxetine BACKGROUND While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder ( MDD ) , the prevalence and importance of painful physical symptoms such as back pain , abdominal pain , and musculoskeletal pain is becoming increasingly appreciated . Antidepressants possessing dual serotonin/norepinephrine ( 5-HT/NE ) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain . The efficacy of duloxetine , a balanced and potent dual reuptake inhibitor of 5-HT and NE , was evaluated within a cohort of depressed patients with associated painful physical symptoms . METHODS In this multicenter , double-blind , placebo-controlled study , patients meeting DSM-IV criteria for MDD were r and omized to receive placebo ( N=141 ) or duloxetine 60 mg QD ( N=141 ) . Patients were required to have a 17-item Hamilton Rating Scale for Depression ( HAMD17 ) total score 15 , a Clinical Global Impression of Severity ( CGI-S ) score 4 , and a Brief Pain Inventory ( BPI ) Average Pain score 2 at baseline . The primary efficacy measure was the BPI Average Pain score , while secondary measures included other BPI items , the HAMD17 total score , CGI-S , the Patient Global Impression of Improvement ( PGI-I ) scale , Visual Analog Scales ( VAS ) for pain , and the Symptom Question naire , Somatic Subscale ( SQSS ) . Safety was evaluated by recording treatment-emergent adverse events ( spontaneously reported ) , vital signs , and laboratory analytes . RESULTS Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits , but only approached significance at endpoint p=0.066 . For the main effect of treatment ( pooling all visits ) , significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items , in addition to VAS overall pain and back pain . Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25 - 50 % , compared with 19 - 39 % for placebo . Mean changes at endpoint in depression rating scales ( HAMD17 , CGI-S , PGI-I ) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response . The magnitude of placebo treatment effects ( as measured by HAMD17 total score and Maier subscale ) was significantly smaller in patients with 1 previous depressive episode , compared to those patients with no previous episodes . In patients with 1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies . Rates of discontinuation due to adverse events were 14.2 % vs. 2.1 % for duloxetine and placebo , respectively p<0.001 . Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea , dry mouth , fatigue , and decreased appetite . CONCLUSIONS In this study , duloxetine ( 60 mg QD ) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression . Improvements in pain severity occurred independently of changes in depressive symptom severity Existing therapies for major depressive disorder ( MDD ) have either limited efficacy and /or poor tolerability . The present study examined the effects of duloxetine , a potent and balanced dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) , in patients with MDD . Adult patients ( N = 267 ) with MDD were r and omly assigned to receive duloxetine ( 60 mg/day ) or placebo in this 9-week , multi-center , double-blind , parallel-group clinical trial . Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale ( HAMD(17 ) ) , Visual Analog Scales ( VAS ) for pain , Clinical Global Impression of Severity ( CGI-S ) , Patient 's Global Impression of Improvement ( PGI-I ) , and Quality of Life in Depression Scale ( QLDS ) . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests .  Duloxetine ( 60 mg QD ) significantly reduced the HAMD(17 ) total score compared with placebo at the end of 9-week therapy . Estimated probabilities of response and remission were 65 and 43 % , respectively , for duloxetine compared with 42 and 28 % for placebo . Duloxetine also reduced overall pain , back pain , shoulder pain and time in pain while awake significantly more than placebo . Global measures of improvement , including PGI-I and QLDS , were significantly improved by duloxetine compared with placebo .  Discontinuations due to adverse events were more frequent for duloxetine-treated patients ( 12.5 % ) than for placebo-treated patients ( 4.3 
    Output:
    
agent
Conclusion Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine .
Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate .
In the absence of relevant data from head-to-head comparison trials , results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine
***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 This analysis assessed the incidence , severity , onset , and duration of nausea among patients with major depressive disorder ( MDD ) treated with the new antidepressant duloxetine .  METHODS Data were pooled from 8 double-blind , r and omized , placebo- and active comparator-controlled trials employing patients with MDD that were su bmi tted to the US Food and Drug Administration to support duloxetine 's new drug application for treatment of MDD . RESULTS The numbers of patients receiving each regimen were as follows : placebo , n = 777 ;  duloxetine 40 mg/d , n = 177 ; duloxetine 60 mg/d , n = 251 ; duloxetine 80 mg/d , n = 363 ; duloxetine 120 mg/d , n = 348 ; paroxetine 20 mg/d , n = 359 ; and fluoxetine 20 mg/d , n = 70 . In acute placebo-controlled trials of duloxetine 40 to 120 mg/d , treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo ( 19.9 % [ 227/1139 ] vs 6.9 % [ 154/777 ] , respectively ; P < 0.001 ) . Among duloxetine-treated patients , the median time to onset of nausea was 1 day , and the median duration of nausea was 7 days . The incidence of nausea was similar to placebo rates after 1 week . In paroxetine-controlled studies , the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine ( 14.4 % vs 12.0 % , respectively ) . In head-to-head studies , the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine ( 17.1 % vs 15.7 % , respectively ) . Most duloxetine-treated patients reported nausea to be mild ( 52.9 % ) or moderate ( 41.4 % ) . Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo ( 1.4 % [ 16/1139 ] vs 0.1 % [ 1/777 ] , respectively ; P = 0.002 ) . Following abrupt discontinuation after acute treatment , 5.9 % of duloxetine-treated patients exhibited nausea compared with 0.3 % of patients receiving placebo ( P < 0.001 ) . The incidence of treatment-emergent nausea during 6-month continuation of duloxetine treatment ( 80 mg/d , 2.1 % ; 120 mg/d , 1.3 % ) was similar to placebo ( 1.6 % ) . Following abrupt discontinuation after 8 months of treatment , nausea was reported by 1.6 % of patients receiving duloxetine 120 mg/d compared with 0 % for those receiving duloxetine 80 mg/d and 0 % for placebo . CONCLUSIONS Duloxetine induced mild to moderate nausea in a subset of patients with MDD during treatment initiation . Nausea resolved rapidly with continued treatment . The incidence of duloxetine-induced nausea resembled that produced by paroxetine and fluoxetine Pramipexole , a dopamine D2 receptor agonist , was tested in 174 patients with major depression , with or without melancholia and without psychotic features . Three daily dose levels ( 0.375 mg , 1.0 mg , and 5.0 mg ) were compared to fluoxetine ( Prozac ) at 20 mg and placebo in a r and omized , double-blind , parallel-group study . After a 1 week placebo run-in period , patients were treated for 8 weeks , had a post- study follow-up ( week 9 ) , and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinician 's Global Impressions-Severity of Illness scale ( CGI-SI ) .  All patients who received one dose of study medication were included in the observed-case analysis ( no missing data were replaced ) . Results indicated that by endpoint ( week 8) , patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D , MADRS , and CGI-SI . Significant improvement in this dose group was seen at other timepoints as well . The most obvious improvement was seen in the pramipexole 5.0 mg group , although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study . Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study . Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day Fluoxetine , a selective serotonin reuptake inhibitor , was compared with mianserin and placebo in a double‐blind study . In total , 81 depressed patients were included . Patients were rated weekly on the Hamilton Depression Rating Scale ( HDRS ) and the Montgomery & Asberg Depression Rating Scale ( MADRS ) . The duration was 6 weeks , and 52 patients completed the study . Significantly more patients on fluoxetine improved than patients on placebo . For mianserin no significant differences were found with either fluoxetine or placebo . Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine , but not for mianserin , than placebo . Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3 . Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7 . Fluoxetine  induced weight loss , while patients on mianserin gained weight . Side effects were present in most patients on the two active drugs ; those on fluoxetine experienced nausea and vomiting , and those on mianserin drowsiness BACKGROUND We compared the efficacy and tolerability of venlafaxine XR with that of fluoxetine in a multicenter , r and omized , double-blind , placebo-controlled study in depressed out patients . METHODS Out patients , 18 years and older , who met DSM-IV criteria for major depressive disorder were included ( n = 301 r and omized ; 232 completed ) . Patients were r and omly assigned to eight weeks of treatment with either venlafaxine XR 75 - 225 mg/day ( n = 100 ) , fluoxetine 20 - 60 mg/day ( n = 103 ) , or placebo ( n = 98 ) . The primary efficacy outcome measures were the final ratings on the Hamilton Rating Scale for Depression ( HAM-D21 ) total score , HAM-D21 depressed mood item , Montgomery-Asberg Depression Rating Scale total score , and Clinical Global Impressions Scale . RESULTS Withdrawal from the study due to adverse events occurred in 6 % of the patients in the venlafaxine XR group and 9 % of the patients in the fluoxetine group . Patients treated with venlafaxine XR , but only rarely those treated with fluoxetine , had statistically significant improvements in their depression ratings compared with placebo at the end of the study . The percentages of patients who achieved full remission of their depression ( HAM-D21 total score < or = 7 ) at the end of treatment were 37 % , 22 % and 18 % for the venlafaxine XR , fluoxetine and placebo groups , respectively . The differences in remission rates between venlafaxine XR and the other groups were statistically significant ( p < 0.05 ) . LIMITATIONS The superior remission outcome observed with venlafaxine XR treatment needs to be replicated in additional studies . CONCLUSION Venlafaxine XR is a well-tolerated and efficacious treatment for depression . The results of this study suggest that venlafaxine XR is as well-tolerated as fluoxetine but may have some efficacy advantages over fluoxetine BACKGROUND While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder ( MDD ) , the prevalence and importance of painful physical symptoms such as back pain , abdominal pain , and musculoskeletal pain is becoming increasingly appreciated . Antidepressants possessing dual serotonin/norepinephrine ( 5-HT/NE ) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain . The efficacy of duloxetine , a balanced and potent dual reuptake inhibitor of 5-HT and NE , was evaluated within a cohort of depressed patients with associated painful physical symptoms . METHODS In this multicenter , double-blind , placebo-controlled study , patients meeting DSM-IV criteria for MDD were r and omized to receive placebo ( N=141 ) or duloxetine 60 mg QD ( N=141 ) . Patients were required to have a 17-item Hamilton Rating Scale for Depression ( HAMD17 ) total score 15 , a Clinical Global Impression of Severity ( CGI-S ) score 4 , and a Brief Pain Inventory ( BPI ) Average Pain score 2 at baseline . The primary efficacy measure was the BPI Average Pain score , while secondary measures included other BPI items , the HAMD17 total score , CGI-S , the Patient Global Impression of Improvement ( PGI-I ) scale , Visual Analog Scales ( VAS ) for pain , and the Symptom Question naire , Somatic Subscale ( SQSS ) . Safety was evaluated by recording treatment-emergent adverse events ( spontaneously reported ) , vital signs , and laboratory analytes . RESULTS Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits , but only approached significance at endpoint p=0.066 . For the main effect of treatment ( pooling all visits ) , significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items , in addition to VAS overall pain and back pain . Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25 - 50 % , compared with 19 - 39 % for placebo . Mean changes at endpoint in depression rating scales ( HAMD17 , CGI-S , PGI-I ) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response . The magnitude of placebo treatment effects ( as measured by HAMD17 total score and Maier subscale ) was significantly smaller in patients with 1 previous depressive episode , compared to those patients with no previous episodes . In patients with 1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies . Rates of discontinuation due to adverse events were 14.2 % vs. 2.1 % for duloxetine and placebo , respectively p<0.001 . Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea , dry mouth , fatigue , and decreased appetite . CONCLUSIONS In this study , duloxetine ( 60 mg QD ) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression . Improvements in pain severity occurred independently of changes in depressive symptom severity Existing therapies for major depressive disorder ( MDD ) have either limited efficacy and /or poor tolerability . The present study examined the effects of duloxetine , a potent and balanced dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) , in patients with MDD . Adult patients ( N = 267 ) with MDD were r and omly assigned to receive duloxetine ( 60 mg/day ) or placebo in this 9-week , multi-center , double-blind , parallel-group clinical trial . Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale ( HAMD(17 ) ) , Visual Analog Scales ( VAS ) for pain , Clinical Global Impression of Severity ( CGI-S ) , Patient 's Global Impression of Improvement ( PGI-I ) , and Quality of Life in Depression Scale ( QLDS ) . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests .  Duloxetine ( 60 mg QD ) significantly reduced the HAMD(17 ) total score compared with placebo at the end of 9-week therapy . Estimated probabilities of response and remission were 65 and 43 % , respectively , for duloxetine compared with 42 and 28 % for placebo . Duloxetine also reduced overall pain , back pain , shoulder pain and time in pain while awake significantly more than placebo . Global measures of improvement , including PGI-I and QLDS , were significantly improved by duloxetine compared with placebo .  Discontinuations due to adverse events were more frequent for duloxetine-treated patients ( 12.5 % ) than for placebo-treated patients ( 4.3 
    Output:
    