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: Background : Major depressive disorder occurs commonly in association with alcohol dependence , both in clinical sample s and in the community . Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results . This multicenter , double-blind , placebo-controlled trial of sertraline was design ed to address many of the potential method ological shortcomings of studies of co-occurring disorders . Method : Following a 1-week , single-blind , placebo lead-in period , 328 patients with co-occurring major depressive disorder and alcohol dependence were r and omly assigned to receive 10 weeks of treatment with sertraline ( at a maximum dose of 200 mg/d ) or matching placebo . R and omization was stratified , based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking , result ing in a sample of 189 patients with Hamilton Depression Rating Scale scores ≥17 ( group A ) and 139 patients with Hamilton Depression Rating Scale scores ≤16 ( group B ) . Results : Both depressive symptoms and alcohol consumption decreased substantially over time in both groups . There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients . Conclusion : Despite careful attention to method ological considerations , this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence . The high rate of response among placebo-treated patients may help to explain these findings . Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder ( MDD ) treatment in adults . This was a 10-week , multicenter , double-blind , placebo-controlled and active-controlled , fixed-dose trial ( NCT01473381 ) . Adult patients with MDD ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , text revision criteria ) were r and omized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day , citalopram 40 mg/day , or placebo . Primary efficacy : Montgomery – Åsberg Depression Rating Scale ( MADRS ) ; secondary efficacy : Clinical Global Impressions-Severity and sustained response ( MADRS total score⩽12 for at least the last two consecutive double-blind visits ) . The intent-to-treat population comprised 1133 patients , ( placebo=281 ; vilazodone 20 mg/day=288 ; vilazodone 40 mg/day=284 ; citalopram=280  ) . MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day , vilazodone 40 mg/day , and citalopram versus  placebo . Sustained response rates were numerically higher , but not significantly different , in all active treatment groups versus placebo . The most common adverse events ( ≥5 % of vilazodone patients , twice the rate of placebo ) were diarrhea , nausea , vomiting  ( vilazodone 40 mg/day only ) , and insomnia . Improved sexual function ( Changes in Sexual Functioning Question naire scores ) was seen in all groups ; between-group differences were not significant . Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD This multicenter study compared the efficacy and safety of citalopram and placebo in a population of moderately to severely depressed patients with melancholia . This r and omized , double-blind , parallel-group study compared citalopram ( flexible dose ; 20 - 80 mg/day ) with placebo in 180 psychiatric out patients with a DSM-III diagnosis of major depression or bipolar disorder , depressed , who also met DSM-III criteria for melancholia . Following a 1-week placebo washout period , patients meeting study entry criteria were r and omized to 4 weeks of double-blind treatment with either citalopram or placebo .  Efficacy measures included the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) Scale , and the Zung Self-Rating Depression Scale . Patients treated with citalopram showed significantly greater improvement at endpoint than placebo patients on the HAM-D , CGI , and Zung scales . On the HAM-D , citalopram patients exhibited significantly greater improvement than placebo patients after 1 week of double-blind treatment and at all subsequent study visits . Endpoint analyses of the HAM-D subscales demonstrated that citalopram produced significant improvement of the psychomotor retardation , cognitive disturbance , sleep disturbance , and melancholia symptom clusters . Nausea , dry mouth , somnolence , dizziness , and increased sweating were reported at higher rates by citalopram-treated patients than by placebo-treated patients , but there were no significant citalopram-placebo differences in the incidence of activation ( e.g. , anxiety , nervousness , insomnia ) or sexual dysfunction . Analysis of electrocardiograms , vital signs , and laboratory tests did not reveal any clinical ly significant effects of citalopram treatment . The results of this study indicate that citalopram is safe and effective in the treatment of depressed patients with melancholia , and is associated with a favorable side effect profile and a potentially rapid onset of action BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness OBJECTIVE Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence . While some studies have demonstrated that antidepressants reduce depressive symptoms in individuals with depression and alcohol dependence , most studies have not found antidepressant treatment helpful in reducing excessive drinking in these patients . The authors provide results from a double-blind , placebo-controlled trial that evaluated the efficacy of combining approved medications for depression ( sertraline ) and alcohol dependence ( naltrexone ) in treating patients with both disorders . METHOD A total of 170 depressed alcohol-dependent patients were r and omly assigned to receive 14 weeks of treatment with sertraline ( 200 mg/day [ N=40 ] ) , naltrexone ( 100 mg/day [ N=49 ] ) , the combination of sertraline plus naltrexone ( N=42 ) , or double placebo ( N=39 ) while receiving weekly cognitive-behavioral therapy . RESULTS The sertraline plus naltrexone combination produced a higher alcohol abstinence rate ( 53.7 % ) and demonstrated a longer delay before relapse to heavy drinking ( median delay=98 days ) than the naltrexone ( abstinence rate : 21.3 % ; delay=29 days ) , sertraline ( abstinence rate : 27.5 % ; delay=23 days ) , and placebo ( abstinence rate : 23.1 % ; delay=26 days ) groups . The number of patients in the medication combination group not depressed by the end of treatment ( 83.3 % ) approached significance when compared with patients in the other treatment groups . The serious adverse event rate was 25.9 % , with fewer reported with the medication combination ( 11.9 % ) than the other treatments . CONCLUSIONS More depressed alcohol-dependent patients receiving the sertraline plus naltrexone combination achieved abstinence from alcohol , had delayed relapse to heavy drinking , reported fewer serious adverse events , and tended to not be depressed by the end of treatment OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo  took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial Agomelatine ( S 20098 ) has a unique and new pharmacological profile . It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors , and has been shown to be active in several animal models of depression . The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder ( DSM-IV criteria ) . The methodology used was a conventional double-blind design comparing three different doses of agomelatine ( 1 , 5 and 25 mg once a day ) with placebo over an 8-week treatment period . Paroxetine was used as the study validator . Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were included . On the pivotal analysis , the mean final HAM-D total score ( Full Analysis Set LOCF ) demonstrated agomelatine 25 mg to be statistically more effective than placebo . This was confirmed by other analyses and criteria ( responders , remission , sub population of severely depressed patients , Montgomery – Åsberg Depression Rating Scale , Clinical Global Impression-Severity of Illness ) . Agomelatine 25 mg alleviated the anxiety associated with depression , as measured on Hamilton Anxiety Scale .  Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to vali date the study methodology and population . Agomelatine , whatever the dose , showed good acceptability with a side-effects profile close to that of placebo . In conclusion , this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose OBJECTIVE Management of depression in elderly patients presents a significant medical challenge , and there is 
    Output:
    
agent
After having corrected for these apparent mistakes , we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age ; while this suggests SSRIs to be safe drugs in the non-elderly , they do confirm what is already known , that is , that they may enhance the risk for SAEs in the old .
***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: Background : Major depressive disorder occurs commonly in association with alcohol dependence , both in clinical sample s and in the community . Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results . This multicenter , double-blind , placebo-controlled trial of sertraline was design ed to address many of the potential method ological shortcomings of studies of co-occurring disorders . Method : Following a 1-week , single-blind , placebo lead-in period , 328 patients with co-occurring major depressive disorder and alcohol dependence were r and omly assigned to receive 10 weeks of treatment with sertraline ( at a maximum dose of 200 mg/d ) or matching placebo . R and omization was stratified , based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking , result ing in a sample of 189 patients with Hamilton Depression Rating Scale scores ≥17 ( group A ) and 139 patients with Hamilton Depression Rating Scale scores ≤16 ( group B ) . Results : Both depressive symptoms and alcohol consumption decreased substantially over time in both groups . There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients . Conclusion : Despite careful attention to method ological considerations , this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence . The high rate of response among placebo-treated patients may help to explain these findings . Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder ( MDD ) treatment in adults . This was a 10-week , multicenter , double-blind , placebo-controlled and active-controlled , fixed-dose trial ( NCT01473381 ) . Adult patients with MDD ( Diagnostic and Statistical Manual of Mental Disorders , 4th ed . , text revision criteria ) were r and omized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day , citalopram 40 mg/day , or placebo . Primary efficacy : Montgomery – Åsberg Depression Rating Scale ( MADRS ) ; secondary efficacy : Clinical Global Impressions-Severity and sustained response ( MADRS total score⩽12 for at least the last two consecutive double-blind visits ) . The intent-to-treat population comprised 1133 patients , ( placebo=281 ; vilazodone 20 mg/day=288 ; vilazodone 40 mg/day=284 ; citalopram=280  ) . MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day , vilazodone 40 mg/day , and citalopram versus  placebo . Sustained response rates were numerically higher , but not significantly different , in all active treatment groups versus placebo . The most common adverse events ( ≥5 % of vilazodone patients , twice the rate of placebo ) were diarrhea , nausea , vomiting  ( vilazodone 40 mg/day only ) , and insomnia . Improved sexual function ( Changes in Sexual Functioning Question naire scores ) was seen in all groups ; between-group differences were not significant . Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD This multicenter study compared the efficacy and safety of citalopram and placebo in a population of moderately to severely depressed patients with melancholia . This r and omized , double-blind , parallel-group study compared citalopram ( flexible dose ; 20 - 80 mg/day ) with placebo in 180 psychiatric out patients with a DSM-III diagnosis of major depression or bipolar disorder , depressed , who also met DSM-III criteria for melancholia . Following a 1-week placebo washout period , patients meeting study entry criteria were r and omized to 4 weeks of double-blind treatment with either citalopram or placebo .  Efficacy measures included the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI ) Scale , and the Zung Self-Rating Depression Scale . Patients treated with citalopram showed significantly greater improvement at endpoint than placebo patients on the HAM-D , CGI , and Zung scales . On the HAM-D , citalopram patients exhibited significantly greater improvement than placebo patients after 1 week of double-blind treatment and at all subsequent study visits . Endpoint analyses of the HAM-D subscales demonstrated that citalopram produced significant improvement of the psychomotor retardation , cognitive disturbance , sleep disturbance , and melancholia symptom clusters . Nausea , dry mouth , somnolence , dizziness , and increased sweating were reported at higher rates by citalopram-treated patients than by placebo-treated patients , but there were no significant citalopram-placebo differences in the incidence of activation ( e.g. , anxiety , nervousness , insomnia ) or sexual dysfunction . Analysis of electrocardiograms , vital signs , and laboratory tests did not reveal any clinical ly significant effects of citalopram treatment . The results of this study indicate that citalopram is safe and effective in the treatment of depressed patients with melancholia , and is associated with a favorable side effect profile and a potentially rapid onset of action BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness OBJECTIVE Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence . While some studies have demonstrated that antidepressants reduce depressive symptoms in individuals with depression and alcohol dependence , most studies have not found antidepressant treatment helpful in reducing excessive drinking in these patients . The authors provide results from a double-blind , placebo-controlled trial that evaluated the efficacy of combining approved medications for depression ( sertraline ) and alcohol dependence ( naltrexone ) in treating patients with both disorders . METHOD A total of 170 depressed alcohol-dependent patients were r and omly assigned to receive 14 weeks of treatment with sertraline ( 200 mg/day [ N=40 ] ) , naltrexone ( 100 mg/day [ N=49 ] ) , the combination of sertraline plus naltrexone ( N=42 ) , or double placebo ( N=39 ) while receiving weekly cognitive-behavioral therapy . RESULTS The sertraline plus naltrexone combination produced a higher alcohol abstinence rate ( 53.7 % ) and demonstrated a longer delay before relapse to heavy drinking ( median delay=98 days ) than the naltrexone ( abstinence rate : 21.3 % ; delay=29 days ) , sertraline ( abstinence rate : 27.5 % ; delay=23 days ) , and placebo ( abstinence rate : 23.1 % ; delay=26 days ) groups . The number of patients in the medication combination group not depressed by the end of treatment ( 83.3 % ) approached significance when compared with patients in the other treatment groups . The serious adverse event rate was 25.9 % , with fewer reported with the medication combination ( 11.9 % ) than the other treatments . CONCLUSIONS More depressed alcohol-dependent patients receiving the sertraline plus naltrexone combination achieved abstinence from alcohol , had delayed relapse to heavy drinking , reported fewer serious adverse events , and tended to not be depressed by the end of treatment OBJECTIVE There have been few placebo-controlled trials of selective serotonin reuptake inhibitors for depressed elderly patients . This placebo-controlled study of sertraline was design ed to confirm the results of non-placebo-controlled trials . METHOD The subjects were out patients age 60 years or older who had a DSM-IV diagnosis of major depressive disorder and a total score on the 17-item Hamilton Depression Rating Scale of 18 or higher . The patients were r and omly assigned to 8 weeks of double-blind treatment with placebo or a flexible daily dose of 50 or 100 mg of sertraline . The primary outcome variables were the Hamilton scale and Clinical Global Impression ( CGI ) scales for severity and improvement . RESULTS A total of 371 patients assigned to sertraline and 376 assigned to placebo  took at least one dose . At endpoint , the patients receiving sertraline evidence d significantly greater improvements than those receiving placebo on the Hamilton depression scale and CGI severity and improvement scales . The mean changes from baseline to endpoint in Hamilton score were -7.4 points ( SD=6.3 ) for sertraline and -6.6 points ( SD=6.4 ) for placebo . The rate of CGI-defined response at endpoint was significantly higher for sertraline ( 45 % ) than for placebo ( 35 % ) , and the time to sustained response was significantly shorter for sertraline ( median , 57 versus 61 days ) . There were few discontinuations due to treatment-related adverse events , 8 % for sertraline and 2 % for placebo . CONCLUSIONS Sertraline was effective and well tolerated by older adults with major depression , although the drug-placebo difference was not large in this 8-week trial Agomelatine ( S 20098 ) has a unique and new pharmacological profile . It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors , and has been shown to be active in several animal models of depression . The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder ( DSM-IV criteria ) . The methodology used was a conventional double-blind design comparing three different doses of agomelatine ( 1 , 5 and 25 mg once a day ) with placebo over an 8-week treatment period . Paroxetine was used as the study validator . Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were included . On the pivotal analysis , the mean final HAM-D total score ( Full Analysis Set LOCF ) demonstrated agomelatine 25 mg to be statistically more effective than placebo . This was confirmed by other analyses and criteria ( responders , remission , sub population of severely depressed patients , Montgomery – Åsberg Depression Rating Scale , Clinical Global Impression-Severity of Illness ) . Agomelatine 25 mg alleviated the anxiety associated with depression , as measured on Hamilton Anxiety Scale .  Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to vali date the study methodology and population . Agomelatine , whatever the dose , showed good acceptability with a side-effects profile close to that of placebo . In conclusion , this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose OBJECTIVE Management of depression in elderly patients presents a significant medical challenge , and there is 
    Output:
    