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 To evaluate the efficacy , and further establish the safety profile , of oral once-daily vilazodone , a potent and selective serotonin 1A receptor partial agonist and reuptake inhibitor , in the treatment of major depressive disorder ( MDD ) . METHOD This phase 3 , r and omized , double-blind , placebo-controlled , 8-week study ( conducted March 2008-February 2009 ) enrolled 481 adults with DSM-IV-TR-defined MDD . Patients received vilazodone ( titrated to 40 mg/d ) or placebo . The primary efficacy endpoint was change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score from baseline to end of treatment . Secondary efficacy measures included MADRS and 17-item Hamilton Depression Rating Scale ( HDRS-17 ) response and change in HDRS-17 , HDRS-21 , Hamilton Anxiety Rating Scale ( HARS ) , Clinical Global Impressions-Severity of Illness ( CGI-S ) , and Clinical Global Impressions-Improvement ( CGI-I ) scores . The Changes in Sexual Functioning Question naire ( CSFQ ) was administered at baseline and week 8 . RESULTS Vilazodone-treated patients had significantly greater improvement ( P = .009 ) according to the MADRS than placebo patients ( intent-to-treat ; least-squares mean changes : -13.3 , -10.8 ) . MADRS response rates were significantly higher with vilazodone than placebo ( 44 % vs 30 % , P = .002 ) . Remission rates for vilazodone were not significantly different based on the MADRS  ( vilazodone , 27.3 % vs placebo , 20.3 % ; P = .066 ) or HDRS-17  ( vilazodone , 24.2 % vs placebo , 17.7 % ; P = .088 ) . Vilazodone-treated patients had significantly greater improvements from baseline in HDRS-17 ( P = .026 ) , HDRS-21 ( P = .029 ) , HARS ( P = .037 ) , CGI-S ( P = .004 ) , and CGI-I ( P = .004 ) scores than placebo patients . Rates of discontinuation due to adverse events were 5.1 % ( vilazodone ) and 1.7 % ( placebo ) . The most common adverse events ( vilazodone vs placebo ) were diarrhea ( 31 % vs 11 % ) , nausea ( 26 % vs 6 % ) , and headache ( 13 % vs 10 % ) . Treatment-related effects on sexual function as measured by the CSFQ were small and similar to placebo . Effects on weight were no different from placebo . CONCLUSIONS Vilazodone 40 mg/d was well tolerated and effective in adult patients with MDD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00683592 Objective This r and omised , double-blind , 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine ( 10–20 mg/day ) versus agomelatine ( 25–50 mg/day ) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin – noradrenaline reuptake inhibitor ( SNRI ) monotherapy . Methods Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine . Primary endpoint was change from baseline to week 8 in the Montgomery – Åsberg Depression Rating Scale ( MADRS ) total score analysed by mixed model for repeated measurements , using a noninferiority test followed by a superiority test . Secondary endpoints included response and remission rates , anxiety symptoms ( Hamilton Anxiety Rating Scale ) , Clinical Global Impression , overall functioning ( Sheehan Disability Scale ) , health-related quality of life ( EuroQol 5 Dimensions ) , productivity ( work limitation question naire ) and family functioning ( Depression and Family Functioning Scale ) . Results Primary endpoint noninferiority was established and vortioxetine ( n = 252 ) was superior to agomelatine ( n = 241 ) by 2.2 MADRS points ( p < 0.01 ) . Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12 ; MADRS , Hamilton Anxiety Rating Scale , Clinical Global Impression , Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards ; work limitation question naire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12 . Fewer patients withdrew because of adverse events with vortioxetine ( 5.9 % vs 9.5 % ) . Adverse events ( incidence ≥5 % ) were nausea , headache , dizziness and somnolence . Conclusions Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy . Vortioxetine was safe and well tolerated CONTEXT Vortioxetine ( Lu AA21004 ) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions : direct modulation of several receptors and inhibition of the serotonin transporter . OBJECTIVE To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in out patients with major depressive disorder . DESIGN , SETTING , AND PARTICIPANTS This 8-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder ( DSM-IV-TR ) . INTERVENTION Eligible subjects were r and omized in 1:1:1 ratio to 1 of 3 treatment arms : vortioxetine 10 mg , vortioxetine 20 mg , or placebo once daily for 8 weeks . Subjects who completed the 8-week trial entered a 2-week blinded discontinuation period to assess potential discontinuation symptoms . MAIN OUTCOME MEASURE The primary endpoint was the least squares mean change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score from baseline . Key secondary outcomes were analyzed in the following prespecified sequential order : MADRS response ( ≥ 50 % decrease from baseline in total score ) , Clinical Global Impressions-Improvement score , change from baseline in MADRS total score in subjects with baseline Hamilton Anxiety Rating Scale score ≥ 20 , MADRS remission ( total score ≤ 10 ) , and change from baseline in Sheehan Disability Scale total score ( all at week 8) . RESULTS A total of 462 subjects were r and omized to placebo ( n = 157 ) , vortioxetine 10 mg ( n = 155 ) , and vortioxetine 20 mg ( n = 150 ) . Mean ( SE ) reductions from baseline in MADRS total score ( week 8) were -10.77 ( ± 0.807 ) , -12.96 ( ± 0.832 ) , and -14.41 ( ± 0.845 ) for the placebo , vortioxetine 10 mg ( P = .058 vs placebo ) , and vortioxetine 20 mg ( P = .002 vs placebo ) groups . MADRS response/remission was achieved in 28.4%/14.2 % , 33.8%/21.4 % , and 39.2%/22.3 % of subjects , respectively , in the 3 groups . Only MADRS response for vortioxetine 20 mg significantly separated from placebo ( P = .044 ) . Treatment was well tolerated , with the most frequently reported adverse events consisting of nausea , headache , diarrhea , and dizziness . CONCLUSIONS Vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in this study population . Overall , vortioxetine was well tolerated in this study . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01163266 Rationale Vortioxetine has reduced depressive symptoms in adults with major depressive disorder ( MDD ) in multiple clinical trials . Objectives The aim of this study is to evaluate the efficacy , safety , and tolerability of vortioxetine 15 and 20 mg vs placebo in adults with MDD . Methods Patients were r and omized 1:1:1:1 to vortioxetine 15 mg , vortioxetine 20 mg , duloxetine 60 mg ( active reference ) , or placebo . The primary efficacy endpoint was mean change in Montgomery – Åsberg Depression Rating Scale ( MADRS ) total score at week 8 ( MMRM ) . Safety/tolerability assessment s included physical examinations , vital signs , laboratory evaluations , electrocardiograms , adverse events ( AEs ) , Columbia – Suicide Severity Rating Scale , Arizona Sexual Experiences Scale , and Discontinuation – Emergent Signs and Symptoms checklist . Results Six hundred and fourteen patients were r and omized . Mean changes in MADRS scores were −12.83 ( ±0.834 ) , −14.30 ( ±0.890 ) , −15.57 ( ±0.880 ) , and −16.90 ( ±0.884 ) for placebo , vortioxetine 15 mg ( P = .224 ) , vortioxetine 20 mg ( P = .023 ) , and duloxetine 60 mg ( P < .001 ) ( P vs placebo ) , respectively . AEs reported by ≥5 % of vortioxetine patients included nausea , headache , diarrhea , dizziness , dry mouth , constipation , vomiting , insomnia , fatigue , and upper respiratory infection . Treatment-emergent sexual dysfunction , suicidal ideation or behavior , and discontinuation symptoms were not significantly different between vortioxetine and placebo . Conclusions Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of treatment . Both vortioxetine doses were well tolerated . Clinical trial registration Clinical Trials.gov identifier NCT01153009 ; www . clinical The efficacy and tolerability of Lu AA21004 in the prevention of relapse of major depressive disorder ( MDD ) in patients in remission after acute treatment was evaluated . Patients ( n=639 ) aged 18–75 years with a primary diagnosis of MDD with a current major depressive episode ( MDE ) ≥4 weeks ’ duration , at least one prior MDE and a MADRS total score ≥26 received 12-week , open-label Lu AA21004 at 5 or 10mg/day . Patients in remission ( MADRS ≤10 ) at both weeks 10 and 12 were assigned to double-blind treatment with either placebo or Lu AA21004 ( fixed dose from Week 8) . Patients ( n=396 ) were treated , after r and om assignment to placebo ( n=192 ) or Lu AA21004 ( n=204 ) . The primary analysis of time to relapse ( full- analysis set , Cox proportional hazard model ) showed a statistically significant difference in favour of Lu AA21004 versus placebo with a hazard ratio of 2.01 ( 95 % confidence interval : 1.26–3.21 ; p=0.0035 ) . The proportion of patients who relapsed was 13 % in the Lu AA21004 group ( n=27 ) and 26 % in the placebo group ( n=50 ) . The withdrawal rates due to adverse events were 8 % ( open-label ) , and 3 % ( placebo ) and 8 % ( Lu AA21004 ) ( double-blind ) . Thus , Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment Owing to the lack of biologically based clinical measures and reliable biomarkers for many indications within the CNS area , the use of imaging tools , such as lig and -based positron emission tomography ( PET ) , has become more and more important in the development of new CNS drugs . A well-grounded and reliable relationship between the plasma concentration of the drug and the occupancy of the receptor ⁄ transporter is a powerful tool to investigate the mechanism of action of a new drug and to guide dose selection The efficacy of vortioxetine 10 and 20 mg/d vs. placebo on cognitive function and depression in adults with recurrent moderate-to-severe major depressive disorder ( MDD ) was evaluated . Patients ( 18–65 yr , N = 602 ) were r and omized ( 1:1:1 ) to vortioxetine  10 or 20 mg/d  or placebo for 8 wk in a double-blind multi-national study . Cognitive function was assessed with objective neuropsychological tests of executive function , processing speed , attention and learning and memory , and a subjective cognitive measure . The primary outcome 
    Output:
    
agent
EXPERT OPINION Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants .
The most common side effects are nausea , vomiting and constipation .
Results of several studies indicate that vortioxetine may have therapeutic effects on cognition ( e.g. , memory and executive functioning ) that exceed that of st and ard antidepressants .
The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise , pending additional long-term data , to become a first-line antidepressant option
***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 To evaluate the efficacy , and further establish the safety profile , of oral once-daily vilazodone , a potent and selective serotonin 1A receptor partial agonist and reuptake inhibitor , in the treatment of major depressive disorder ( MDD ) . METHOD This phase 3 , r and omized , double-blind , placebo-controlled , 8-week study ( conducted March 2008-February 2009 ) enrolled 481 adults with DSM-IV-TR-defined MDD . Patients received vilazodone ( titrated to 40 mg/d ) or placebo . The primary efficacy endpoint was change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score from baseline to end of treatment . Secondary efficacy measures included MADRS and 17-item Hamilton Depression Rating Scale ( HDRS-17 ) response and change in HDRS-17 , HDRS-21 , Hamilton Anxiety Rating Scale ( HARS ) , Clinical Global Impressions-Severity of Illness ( CGI-S ) , and Clinical Global Impressions-Improvement ( CGI-I ) scores . The Changes in Sexual Functioning Question naire ( CSFQ ) was administered at baseline and week 8 . RESULTS Vilazodone-treated patients had significantly greater improvement ( P = .009 ) according to the MADRS than placebo patients ( intent-to-treat ; least-squares mean changes : -13.3 , -10.8 ) . MADRS response rates were significantly higher with vilazodone than placebo ( 44 % vs 30 % , P = .002 ) . Remission rates for vilazodone were not significantly different based on the MADRS  ( vilazodone , 27.3 % vs placebo , 20.3 % ; P = .066 ) or HDRS-17  ( vilazodone , 24.2 % vs placebo , 17.7 % ; P = .088 ) . Vilazodone-treated patients had significantly greater improvements from baseline in HDRS-17 ( P = .026 ) , HDRS-21 ( P = .029 ) , HARS ( P = .037 ) , CGI-S ( P = .004 ) , and CGI-I ( P = .004 ) scores than placebo patients . Rates of discontinuation due to adverse events were 5.1 % ( vilazodone ) and 1.7 % ( placebo ) . The most common adverse events ( vilazodone vs placebo ) were diarrhea ( 31 % vs 11 % ) , nausea ( 26 % vs 6 % ) , and headache ( 13 % vs 10 % ) . Treatment-related effects on sexual function as measured by the CSFQ were small and similar to placebo . Effects on weight were no different from placebo . CONCLUSIONS Vilazodone 40 mg/d was well tolerated and effective in adult patients with MDD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00683592 Objective This r and omised , double-blind , 12-week study compared efficacy and tolerability of flexible-dose treatment with vortioxetine ( 10–20 mg/day ) versus agomelatine ( 25–50 mg/day ) in major depressive disorder patients with inadequate response to selective serotonin reuptake inhibitor (SSRI)/serotonin – noradrenaline reuptake inhibitor ( SNRI ) monotherapy . Methods Patients were switched directly from SSRI/SNRI to vortioxetine or agomelatine . Primary endpoint was change from baseline to week 8 in the Montgomery – Åsberg Depression Rating Scale ( MADRS ) total score analysed by mixed model for repeated measurements , using a noninferiority test followed by a superiority test . Secondary endpoints included response and remission rates , anxiety symptoms ( Hamilton Anxiety Rating Scale ) , Clinical Global Impression , overall functioning ( Sheehan Disability Scale ) , health-related quality of life ( EuroQol 5 Dimensions ) , productivity ( work limitation question naire ) and family functioning ( Depression and Family Functioning Scale ) . Results Primary endpoint noninferiority was established and vortioxetine ( n = 252 ) was superior to agomelatine ( n = 241 ) by 2.2 MADRS points ( p < 0.01 ) . Vortioxetine was also significantly superior in response and remission rates at weeks 8 and 12 ; MADRS , Hamilton Anxiety Rating Scale , Clinical Global Impression , Sheehan Disability Scale and EuroQol 5 Dimensions scores at week 4 onwards ; work limitation question naire at week 8 and Depression and Family Functioning Scale at weeks 8 and 12 . Fewer patients withdrew because of adverse events with vortioxetine ( 5.9 % vs 9.5 % ) . Adverse events ( incidence ≥5 % ) were nausea , headache , dizziness and somnolence . Conclusions Vortioxetine was noninferior and significantly superior to agomelatine in major depressive disorder patients with previous inadequate response to a single course of SSRI/SNRI monotherapy . Vortioxetine was safe and well tolerated CONTEXT Vortioxetine ( Lu AA21004 ) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions : direct modulation of several receptors and inhibition of the serotonin transporter . OBJECTIVE To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in out patients with major depressive disorder . DESIGN , SETTING , AND PARTICIPANTS This 8-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder ( DSM-IV-TR ) . INTERVENTION Eligible subjects were r and omized in 1:1:1 ratio to 1 of 3 treatment arms : vortioxetine 10 mg , vortioxetine 20 mg , or placebo once daily for 8 weeks . Subjects who completed the 8-week trial entered a 2-week blinded discontinuation period to assess potential discontinuation symptoms . MAIN OUTCOME MEASURE The primary endpoint was the least squares mean change in Montgomery-Asberg Depression Rating Scale ( MADRS ) total score from baseline . Key secondary outcomes were analyzed in the following prespecified sequential order : MADRS response ( ≥ 50 % decrease from baseline in total score ) , Clinical Global Impressions-Improvement score , change from baseline in MADRS total score in subjects with baseline Hamilton Anxiety Rating Scale score ≥ 20 , MADRS remission ( total score ≤ 10 ) , and change from baseline in Sheehan Disability Scale total score ( all at week 8) . RESULTS A total of 462 subjects were r and omized to placebo ( n = 157 ) , vortioxetine 10 mg ( n = 155 ) , and vortioxetine 20 mg ( n = 150 ) . Mean ( SE ) reductions from baseline in MADRS total score ( week 8) were -10.77 ( ± 0.807 ) , -12.96 ( ± 0.832 ) , and -14.41 ( ± 0.845 ) for the placebo , vortioxetine 10 mg ( P = .058 vs placebo ) , and vortioxetine 20 mg ( P = .002 vs placebo ) groups . MADRS response/remission was achieved in 28.4%/14.2 % , 33.8%/21.4 % , and 39.2%/22.3 % of subjects , respectively , in the 3 groups . Only MADRS response for vortioxetine 20 mg significantly separated from placebo ( P = .044 ) . Treatment was well tolerated , with the most frequently reported adverse events consisting of nausea , headache , diarrhea , and dizziness . CONCLUSIONS Vortioxetine 20 mg significantly reduced MADRS total score at 8 weeks in this study population . Overall , vortioxetine was well tolerated in this study . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01163266 Rationale Vortioxetine has reduced depressive symptoms in adults with major depressive disorder ( MDD ) in multiple clinical trials . Objectives The aim of this study is to evaluate the efficacy , safety , and tolerability of vortioxetine 15 and 20 mg vs placebo in adults with MDD . Methods Patients were r and omized 1:1:1:1 to vortioxetine 15 mg , vortioxetine 20 mg , duloxetine 60 mg ( active reference ) , or placebo . The primary efficacy endpoint was mean change in Montgomery – Åsberg Depression Rating Scale ( MADRS ) total score at week 8 ( MMRM ) . Safety/tolerability assessment s included physical examinations , vital signs , laboratory evaluations , electrocardiograms , adverse events ( AEs ) , Columbia – Suicide Severity Rating Scale , Arizona Sexual Experiences Scale , and Discontinuation – Emergent Signs and Symptoms checklist . Results Six hundred and fourteen patients were r and omized . Mean changes in MADRS scores were −12.83 ( ±0.834 ) , −14.30 ( ±0.890 ) , −15.57 ( ±0.880 ) , and −16.90 ( ±0.884 ) for placebo , vortioxetine 15 mg ( P = .224 ) , vortioxetine 20 mg ( P = .023 ) , and duloxetine 60 mg ( P < .001 ) ( P vs placebo ) , respectively . AEs reported by ≥5 % of vortioxetine patients included nausea , headache , diarrhea , dizziness , dry mouth , constipation , vomiting , insomnia , fatigue , and upper respiratory infection . Treatment-emergent sexual dysfunction , suicidal ideation or behavior , and discontinuation symptoms were not significantly different between vortioxetine and placebo . Conclusions Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of treatment . Both vortioxetine doses were well tolerated . Clinical trial registration Clinical Trials.gov identifier NCT01153009 ; www . clinical The efficacy and tolerability of Lu AA21004 in the prevention of relapse of major depressive disorder ( MDD ) in patients in remission after acute treatment was evaluated . Patients ( n=639 ) aged 18–75 years with a primary diagnosis of MDD with a current major depressive episode ( MDE ) ≥4 weeks ’ duration , at least one prior MDE and a MADRS total score ≥26 received 12-week , open-label Lu AA21004 at 5 or 10mg/day . Patients in remission ( MADRS ≤10 ) at both weeks 10 and 12 were assigned to double-blind treatment with either placebo or Lu AA21004 ( fixed dose from Week 8) . Patients ( n=396 ) were treated , after r and om assignment to placebo ( n=192 ) or Lu AA21004 ( n=204 ) . The primary analysis of time to relapse ( full- analysis set , Cox proportional hazard model ) showed a statistically significant difference in favour of Lu AA21004 versus placebo with a hazard ratio of 2.01 ( 95 % confidence interval : 1.26–3.21 ; p=0.0035 ) . The proportion of patients who relapsed was 13 % in the Lu AA21004 group ( n=27 ) and 26 % in the placebo group ( n=50 ) . The withdrawal rates due to adverse events were 8 % ( open-label ) , and 3 % ( placebo ) and 8 % ( Lu AA21004 ) ( double-blind ) . Thus , Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment Owing to the lack of biologically based clinical measures and reliable biomarkers for many indications within the CNS area , the use of imaging tools , such as lig and -based positron emission tomography ( PET ) , has become more and more important in the development of new CNS drugs . A well-grounded and reliable relationship between the plasma concentration of the drug and the occupancy of the receptor ⁄ transporter is a powerful tool to investigate the mechanism of action of a new drug and to guide dose selection The efficacy of vortioxetine 10 and 20 mg/d vs. placebo on cognitive function and depression in adults with recurrent moderate-to-severe major depressive disorder ( MDD ) was evaluated . Patients ( 18–65 yr , N = 602 ) were r and omized ( 1:1:1 ) to vortioxetine  10 or 20 mg/d  or placebo for 8 wk in a double-blind multi-national study . Cognitive function was assessed with objective neuropsychological tests of executive function , processing speed , attention and learning and memory , and a subjective cognitive measure . The primary outcome 
    Output:
    