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: CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy 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 AIM The main purpose of this study was to evaluate the efficacy of paroxetine controlled-release ( CR ) formulation compared to placebo . A secondary objective was to test the hypothesis that the CR decreases selective-serotonin-reuptake-inhibitors-induced nausea as its formulation allows more distal gastrointestinal absorption than the paroxetine immediate-release ( IR ) formulation . METHODS We conducted this study in Japanese and Korean patients with major depressive disorder ( MDD ) in order to demonstrate the efficacy and safety of paroxetine CR compared with placebo . The primary efficacy end-point was the adjusted mean change from baseline in the 17-item Hamilton Rating Scale for Depression total score at Week 8 . RESULTS A total of 416 patients with MDD were r and omly assigned to the CR , IR and placebo groups . The mean change from baseline in the 17-item Hamilton Rating Scale for Depression was -12.8 in the CR group , -12.5 in the IR group , and -10.4 in the placebo group , which showed a statistically significant difference compared to placebo in CR ( P < 0.001 ) and IR ( P = 0.015 ) . The incidence of adverse events was 65 % in CR , 69 % in IR and 55 % in placebo . The adverse events were mostly mild or moderate in severity . In the early treatment period , when initiated from 12.5 mg , the incidence of nausea in the CR group was 6 % , which was comparable with that of placebo ( 5 % ) . CONCLUSION Paroxetine CR is efficacious in the acute treatment of MDD and may have the potential benefit of decreasing the incidence of nausea in the early treatment period The efficacy and safety of fluvoxamine maleate , a selective serotonin reuptake inhibitor , was compared with placebo and imipramine in patients with major depressive disorder . Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression ; however , this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine ( 80 - 240 mg/day ) . After a 1- to 2-week , single-blind , placebo washout phase , 150 depressed out patients were r and omized to double-blind treatment with fluvoxamine maleate ( 50 - 150 mg/day ) , imipramine ( 80 - 240 mg/day ) , or placebo for 6 weeks . Fluvoxamine produced a significant therapeutic benefit over placebo ( p < or = 0.05 ) as assessed by the total score on the Hamilton Rating Scale for Depression ; imipramine ( 80 - 240 mg/day ) produced similar results . The secondary outcome variables ( i.e. , Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor ) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study . Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients . As expected from the pharmacology of these agents , the imipramine groups reported more anticholinergic effects ( dry mouth , dizziness , and urinary retention ) and electrocardiographic effects , whereas the fluvoxamine group reported more nausea , somnolence , and abnormal ejaculation . The majority of these adverse events were mild to moderate and , with the exception of dry mouth ( imipramine ) and abnormal ejaculation ( fluvoxamine ) , were transient . The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate ( 50 - 150 mg/day ) as compared with placebo ; it is also as effective as the tricyclic antidepressant imipramine ( 80 - 240 mg/day ) in patients with major depressive disorder 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 BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression .  Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % 
    Output:
    
agent
Our systematic review in BMC Psychiatry concluded that selective serotonin reuptake inhibitors ( SSRIs ) compared with placebo significantly increase the risk of serious adverse events ( SAEs ) in patients with major depression and the potential beneficial effects of SSRIs seem to be outweighed by the harms .
In their post-hoc analysis of our data , they reported that SSRIs only increase the risk of SAEs in elderly and seems safe for non-elderly patients .
***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: CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy 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 AIM The main purpose of this study was to evaluate the efficacy of paroxetine controlled-release ( CR ) formulation compared to placebo . A secondary objective was to test the hypothesis that the CR decreases selective-serotonin-reuptake-inhibitors-induced nausea as its formulation allows more distal gastrointestinal absorption than the paroxetine immediate-release ( IR ) formulation . METHODS We conducted this study in Japanese and Korean patients with major depressive disorder ( MDD ) in order to demonstrate the efficacy and safety of paroxetine CR compared with placebo . The primary efficacy end-point was the adjusted mean change from baseline in the 17-item Hamilton Rating Scale for Depression total score at Week 8 . RESULTS A total of 416 patients with MDD were r and omly assigned to the CR , IR and placebo groups . The mean change from baseline in the 17-item Hamilton Rating Scale for Depression was -12.8 in the CR group , -12.5 in the IR group , and -10.4 in the placebo group , which showed a statistically significant difference compared to placebo in CR ( P < 0.001 ) and IR ( P = 0.015 ) . The incidence of adverse events was 65 % in CR , 69 % in IR and 55 % in placebo . The adverse events were mostly mild or moderate in severity . In the early treatment period , when initiated from 12.5 mg , the incidence of nausea in the CR group was 6 % , which was comparable with that of placebo ( 5 % ) . CONCLUSION Paroxetine CR is efficacious in the acute treatment of MDD and may have the potential benefit of decreasing the incidence of nausea in the early treatment period The efficacy and safety of fluvoxamine maleate , a selective serotonin reuptake inhibitor , was compared with placebo and imipramine in patients with major depressive disorder . Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression ; however , this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine ( 80 - 240 mg/day ) . After a 1- to 2-week , single-blind , placebo washout phase , 150 depressed out patients were r and omized to double-blind treatment with fluvoxamine maleate ( 50 - 150 mg/day ) , imipramine ( 80 - 240 mg/day ) , or placebo for 6 weeks . Fluvoxamine produced a significant therapeutic benefit over placebo ( p < or = 0.05 ) as assessed by the total score on the Hamilton Rating Scale for Depression ; imipramine ( 80 - 240 mg/day ) produced similar results . The secondary outcome variables ( i.e. , Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor ) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study . Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients . As expected from the pharmacology of these agents , the imipramine groups reported more anticholinergic effects ( dry mouth , dizziness , and urinary retention ) and electrocardiographic effects , whereas the fluvoxamine group reported more nausea , somnolence , and abnormal ejaculation . The majority of these adverse events were mild to moderate and , with the exception of dry mouth ( imipramine ) and abnormal ejaculation ( fluvoxamine ) , were transient . The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate ( 50 - 150 mg/day ) as compared with placebo ; it is also as effective as the tricyclic antidepressant imipramine ( 80 - 240 mg/day ) in patients with major depressive disorder 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 BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p < .002 vs. placebo ) , 65 % of paroxetine IR patients ( p = .06 vs. placebo ) , and 52 % of placebo patients . Remission , defined as a HAM-D total score < or = 7 , was achieved by 43 % of paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( < or = 2 years ) depression .  Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % 
    Output:
    