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 compare the efficacy of imipramine and fluvoxamine in in patients from two centers suffering from a depressive disorder according to DSM IV criteria . Methods The study included 141 patients with a depressive disorder according to DSM IV criteria . After a drug-free and placebo run-in period of 1 week , patients were r and omized to imipramine or fluvoxamine ; doses of both drugs were adjusted to a predefined target blood level . Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level . Results The mean age of the study group ( 47 males , 94 females ) was 51.8 ( range 19–65 ) years . Of these 141 patients , 56 had episode duration longer than 1 year , 48 had mood congruent psychotic features , and 138 patients received medication . Seven patients did not complete the medication trial . The total number of patients using concurrent medication was 12/138 ( 8.6 % ) . On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI ( χ2 exact trend test=4.089 , df=1 , P=0.048 ) . There was no significant difference in 50 % or more reduction on the HRSD , the other primary outcome criterion . On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group ( mean difference=3.1 , st and ard error (SE)=1.4 , t=2.15 , df=136 , P=0.033 ) . There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation . Conclusions In depressed in patients imipramine is more efficacious than fluvoxamine . Both drugs were well tolerated by all patients Research on treatment-resistant depression in the elderly has been limited , and recommendations for clinical man agement have often been extrapolated from studies using nongeriatric patients . This report describes a series of 10 elderly patients with refractory depression who were treated with nortriptyline  after failing to respond to an ade quate trial of a serotonin reuptake inhibitor .  Seven ( 70 % ) of the patients responded to the addition or substitution of nortriptyline . All seven of the responders have remained on nortriptyline for maintenance therapy , none of whom have experienced recurrence of their depression after an average treatment duration of 1 year . Response to nor triptyline  occurred in about 4 weeks in most patients . The mean daily dose of nortriptyline  was 54 mg , and the mean plasma level was 97 ng/mL. Minor side effects occurred in three patients . No patients developed significant electrocardiogram changes .  Nortriptyline , possibly due to its different mechanism of action , may be effective as either an adjunctive or replacement antidepressant in some cases of geriatric depression that are resistant to sero tonin reuptake inhibitors . ( J Geriatr Psychiatry Neurol 2001 ; 14:28 - 32 ) Tricyclic antidepressant ( TCA ) medications are among the most widely used pharmacologic treatments for depression . However , a substantial number of patients fail to respond to these agents . Few st and ardized trials of pharmacologic treatments for TCA nonresponders are available . Bupropion has an apparently different mechanism of action than TCAs and represents a possible treatment for the TCA nonresponder . Based on positive results from pilot studies , a st and ardized study evaluating bupropion in TCA nonresponders was conducted . Forty-one depressed out patients who had failed to respond to adequate documented TCA treatment , defined by specific criteria of dosage , duration , and plasma concentrations , entered a 1-week single-blind placebo phase , followed by an open 8-week bupropion treatment phase utilizing doses of up to the maximum daily dose of 450 mg . Response was measured by change on the Hamilton Depression Rating Scale ( HAM-D ) , Clinical Global Impressions-Severity ( CGI-S ) and Improvement ( CGI-I ) Scales , and the Hamilton Anxiety Rating Scale ( HAM-A ) .  Bupropion treatment result ed in an improvement in depression on all outcome measures . Forty-nine percent were considered " responders , " in that they achieved > or = 50 % improvement on the 28-item HAM-D. Fifty-four percent were classified as responders based on a CGI-I rating of much or very much improved . Statistically significant improvement in depressive symptoms , measured by mean scores for the HAM-D , CGI-S , and HAM-A , was achieved at the end of the study ( as compared to baseline ) . Twelve patients ( 32 % ) had a HAM-D score of < or = 10 at termination . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Although clinicians frequently add a second medication to an initial , ineffective antidepressant drug , no r and omized controlled trial has compared the efficacy of this approach . METHODS We r and omly assigned 565 adult out patients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy  ( mean final dose , 55 mg per day ) to receive sustained-release bupropion ( at a dose of up to 400 mg per day ) as augmentation and 286 to receive buspirone ( at a dose of up to 60 mg per day ) as augmentation . The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of this study ; scores were obtained over the telephone by raters blinded to treatment assignment . The 16-item Quick Inventory of Depressive Symptomatology -- Self-Report ( QIDS-SR-16 ) was used to determine the secondary outcomes of remission ( defined as a score of less than 6 at the end of this study ) and response ( a reduction in baseline scores of 50 percent or more ) . RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission ( 29.7 percent and 30.1 percent , respectively ) , QIDS-SR-16 remission ( 39.0 percent and 32.9 percent ) , and QIDS-SR-16 response ( 31.8 percent and 26.9 percent ) . Sustained-release bupropion , however , was associated with a greater reduction ( from baseline to the end of this study ) in QIDS-SR-16 scores than was buspirone ( 25.3 percent vs. 17.1 percent , P<0.04 ) , a lower QIDS-SR-16 score at the end of this study ( 8.0 vs. 9.1 , P<0.02 ) , and a lower dropout rate due to intolerance ( 12.5 percent vs. 20.6 percent , P<0.009 ) . CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical setting s. Augmentation with sustained-release bupropion does have certain advantages , including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events . ( Clinical Trials.gov number , NCT00021528 . ) About 30 % of depressed patients exhibit depression that is resistant to antidepressant treatment . This resistance may be primary or associated with a concomitant psychiatric or somatic disease . Venlafaxine has shown potent efficacy in certain severe depressions in in- patients and in patients presenting with resistant depression in an open-label study . It was considered of interest to compare , under double-blind , the efficacy of venlafaxine ( 200 to 300 mg/day ) and that of paroxetine ( 30 to 40 mg/day ) ( for 6 weeks ) in 123 patients presenting with major depression resistant to two correctly conducted antidepressant treatments in the course of an episode of depression of duration not exceeding 8 months . The patients were required not to present with organic disease , particularly endocrine disease . After 28 days of treatment , half of the patients receiving venlafaxine and one third of the patients receiving paroxetine showed a 50 % reduction in their total score on the Hamilton scale . In addition , the percentage of patients presenting with remission was significantly higher in the group receiving venlafaxine ( 42 % ) compared to that receiving paroxetine ( 20 % ) . These results require confirmation over the long term and in other forms of resistant depression As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy , research studies with broader aims will become increasingly important . R and omized trials may need to accommo date multiple treatment options . In completely r and omized design s , patients are assigned at r and om to one of the options , requiring that patients and clinicians find each of the options acceptable . In " clinician 's choice " design s , patients are r and omized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician . The clinician 's choice design permits some scope to patient and clinician preferences , but sacrifices the ability to make r and omization-based comparisons of specific options . We describe a new approach , which we call the " equipoise stratified " design , that merges the advantages and avoids the disadvantages of the other two design s for clinical trials . The three design s are contrasted , using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example BACKGROUND We assessed the tolerability and utility of switching fluoxetine nonresponders to citalopram the day that fluoxetine therapy was stopped . METHOD Fifty-eight out patients with DSM-IV major depressive episode and prospect ively confirmed nonresponse to fluoxetine ( mean final dose = 31 mg/day ) were switched directly to citalopram ( 20 mg/day ) . Of the 58 patients , 44 ( 76 % ) had never been successfully treated with antidepressant medication . During a 12-week open-label treatment period , citalopram could be titrated up to a maximum dose of 60 mg/day . Response was evaluated using the Clinical Global Impressions ( CGI ) scale , the 24-item Hamilton Rating Scale for Depression , and several other measures . RESULTS Eighty-one percent ( N = 47 ) completed the trial , and citalopram ( mean dose = 38.8 mg/day ) was well tolerated . The intent-to-treat CGI response rate was 46 % ( 26/57 ) at week 6 and 63 % ( 36/57 ) at study endpoint ; the completer response rate was 76 % among the 47 patients who completed the 12-week trial . Improvement from baseline on all dependent measures was statistically significant after the first week of citalopram treatment . CONCLUSION Fluoxetine nonresponders can be quickly switched to citalopram , with good tolerability and reasonable chance of therapeutic benefit . Further work is necessary to assess the merits of this treatment strategy relative to other options BACKGROUND Approximately half of patients who are prescribed selective serotonin re-uptake inhibitors ( SSRIs ) either do not respond to treatment or do not experience a sustained response . OBJECTIVE The purpose of this study was to assess the efficacy of venlafaxine immediate-release ( IR ) and extended-release ( XR ) in out patients who either did not respond to SSRI treatment or did not maintain a sustained response . METHODS Out patients who met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for major depressive disorder who were previously treated with an SSRI ( fluoxetine > or = 20 mg/d ; sertraline > or = 50 mg/d ; paroxetine > or = 20 mg/d ) for > or = 6 weeks , but demonstrated an inadequate or unsustained response , were switched  to venlafaxine ( IR or XR formulation , 50 - 400 mg/d , titrated from 37.5 mg/d ) for > or = 6 weeks . Response at 6 to 8 weeks was defined as total score < or = 10 on the modified 25-item Hamilton Depression ( HAM-D25 ) rating scale or total score > or = 5 on the 21-item Patient Global Improvement ( PGI-21 ) scale . Remission was defined as a HAM-D25 total score < or = 8 or PGI-21 score > or = 7 . Tests were administered by an unblinded , board-certified psychiatrist . RESULTS A total of 73 patients ( 54 women , 19 men ; mean age , 38.6 years ) were enrolled and treated with venlafaxine IR ( n = 63 ) or venlafaxine XR ( n = 10 ) ; 33 were SSRI nonresponders and 36 had an unsustained response to SSRI treatment . Four patients receiving venlafaxine IR discontinued due to drug-related adverse events ( agitation , sedation , or nausea ) . Data from these patients were excluded from the analysis . After 6 to 8 weeks of treatment , 94.2 % ( 65/69 ) of patients were considered responders ( HAM-D25 or PGI-21 criteria ) ; 91.3 % ( 63/69 ) of patients responded to treatment as assessed by both measures . Eighty-seven percent ( 60/69 ) and 85.5 % ( 59/69 ) of patients achieved remission based on HAM-D,5 and PGI 
    Output:
    
agent
The number of previous treatments with antidepressants was negatively correlated with treatment outcome .
After a first SSRI , any switch within or between classes of antidepressants appears legitimate ( second SSRI , novel dual-acting antidepressants , selective norepinephrine or nor-adrenergic/dopaminergic agents , or tricyclic anti-depressant or mianserin ) .
No unequivocal evidence is available to prove an advantage of a between-class switch .
***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 compare the efficacy of imipramine and fluvoxamine in in patients from two centers suffering from a depressive disorder according to DSM IV criteria . Methods The study included 141 patients with a depressive disorder according to DSM IV criteria . After a drug-free and placebo run-in period of 1 week , patients were r and omized to imipramine or fluvoxamine ; doses of both drugs were adjusted to a predefined target blood level . Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level . Results The mean age of the study group ( 47 males , 94 females ) was 51.8 ( range 19–65 ) years . Of these 141 patients , 56 had episode duration longer than 1 year , 48 had mood congruent psychotic features , and 138 patients received medication . Seven patients did not complete the medication trial . The total number of patients using concurrent medication was 12/138 ( 8.6 % ) . On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI ( χ2 exact trend test=4.089 , df=1 , P=0.048 ) . There was no significant difference in 50 % or more reduction on the HRSD , the other primary outcome criterion . On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group ( mean difference=3.1 , st and ard error (SE)=1.4 , t=2.15 , df=136 , P=0.033 ) . There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation . Conclusions In depressed in patients imipramine is more efficacious than fluvoxamine . Both drugs were well tolerated by all patients Research on treatment-resistant depression in the elderly has been limited , and recommendations for clinical man agement have often been extrapolated from studies using nongeriatric patients . This report describes a series of 10 elderly patients with refractory depression who were treated with nortriptyline  after failing to respond to an ade quate trial of a serotonin reuptake inhibitor .  Seven ( 70 % ) of the patients responded to the addition or substitution of nortriptyline . All seven of the responders have remained on nortriptyline for maintenance therapy , none of whom have experienced recurrence of their depression after an average treatment duration of 1 year . Response to nor triptyline  occurred in about 4 weeks in most patients . The mean daily dose of nortriptyline  was 54 mg , and the mean plasma level was 97 ng/mL. Minor side effects occurred in three patients . No patients developed significant electrocardiogram changes .  Nortriptyline , possibly due to its different mechanism of action , may be effective as either an adjunctive or replacement antidepressant in some cases of geriatric depression that are resistant to sero tonin reuptake inhibitors . ( J Geriatr Psychiatry Neurol 2001 ; 14:28 - 32 ) Tricyclic antidepressant ( TCA ) medications are among the most widely used pharmacologic treatments for depression . However , a substantial number of patients fail to respond to these agents . Few st and ardized trials of pharmacologic treatments for TCA nonresponders are available . Bupropion has an apparently different mechanism of action than TCAs and represents a possible treatment for the TCA nonresponder . Based on positive results from pilot studies , a st and ardized study evaluating bupropion in TCA nonresponders was conducted . Forty-one depressed out patients who had failed to respond to adequate documented TCA treatment , defined by specific criteria of dosage , duration , and plasma concentrations , entered a 1-week single-blind placebo phase , followed by an open 8-week bupropion treatment phase utilizing doses of up to the maximum daily dose of 450 mg . Response was measured by change on the Hamilton Depression Rating Scale ( HAM-D ) , Clinical Global Impressions-Severity ( CGI-S ) and Improvement ( CGI-I ) Scales , and the Hamilton Anxiety Rating Scale ( HAM-A ) .  Bupropion treatment result ed in an improvement in depression on all outcome measures . Forty-nine percent were considered " responders , " in that they achieved > or = 50 % improvement on the 28-item HAM-D. Fifty-four percent were classified as responders based on a CGI-I rating of much or very much improved . Statistically significant improvement in depressive symptoms , measured by mean scores for the HAM-D , CGI-S , and HAM-A , was achieved at the end of the study ( as compared to baseline ) . Twelve patients ( 32 % ) had a HAM-D score of < or = 10 at termination . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Although clinicians frequently add a second medication to an initial , ineffective antidepressant drug , no r and omized controlled trial has compared the efficacy of this approach . METHODS We r and omly assigned 565 adult out patients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy  ( mean final dose , 55 mg per day ) to receive sustained-release bupropion ( at a dose of up to 400 mg per day ) as augmentation and 286 to receive buspirone ( at a dose of up to 60 mg per day ) as augmentation . The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of this study ; scores were obtained over the telephone by raters blinded to treatment assignment . The 16-item Quick Inventory of Depressive Symptomatology -- Self-Report ( QIDS-SR-16 ) was used to determine the secondary outcomes of remission ( defined as a score of less than 6 at the end of this study ) and response ( a reduction in baseline scores of 50 percent or more ) . RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission ( 29.7 percent and 30.1 percent , respectively ) , QIDS-SR-16 remission ( 39.0 percent and 32.9 percent ) , and QIDS-SR-16 response ( 31.8 percent and 26.9 percent ) . Sustained-release bupropion , however , was associated with a greater reduction ( from baseline to the end of this study ) in QIDS-SR-16 scores than was buspirone ( 25.3 percent vs. 17.1 percent , P<0.04 ) , a lower QIDS-SR-16 score at the end of this study ( 8.0 vs. 9.1 , P<0.02 ) , and a lower dropout rate due to intolerance ( 12.5 percent vs. 20.6 percent , P<0.009 ) . CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical setting s. Augmentation with sustained-release bupropion does have certain advantages , including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events . ( Clinical Trials.gov number , NCT00021528 . ) About 30 % of depressed patients exhibit depression that is resistant to antidepressant treatment . This resistance may be primary or associated with a concomitant psychiatric or somatic disease . Venlafaxine has shown potent efficacy in certain severe depressions in in- patients and in patients presenting with resistant depression in an open-label study . It was considered of interest to compare , under double-blind , the efficacy of venlafaxine ( 200 to 300 mg/day ) and that of paroxetine ( 30 to 40 mg/day ) ( for 6 weeks ) in 123 patients presenting with major depression resistant to two correctly conducted antidepressant treatments in the course of an episode of depression of duration not exceeding 8 months . The patients were required not to present with organic disease , particularly endocrine disease . After 28 days of treatment , half of the patients receiving venlafaxine and one third of the patients receiving paroxetine showed a 50 % reduction in their total score on the Hamilton scale . In addition , the percentage of patients presenting with remission was significantly higher in the group receiving venlafaxine ( 42 % ) compared to that receiving paroxetine ( 20 % ) . These results require confirmation over the long term and in other forms of resistant depression As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy , research studies with broader aims will become increasingly important . R and omized trials may need to accommo date multiple treatment options . In completely r and omized design s , patients are assigned at r and om to one of the options , requiring that patients and clinicians find each of the options acceptable . In " clinician 's choice " design s , patients are r and omized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician . The clinician 's choice design permits some scope to patient and clinician preferences , but sacrifices the ability to make r and omization-based comparisons of specific options . We describe a new approach , which we call the " equipoise stratified " design , that merges the advantages and avoids the disadvantages of the other two design s for clinical trials . The three design s are contrasted , using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example BACKGROUND We assessed the tolerability and utility of switching fluoxetine nonresponders to citalopram the day that fluoxetine therapy was stopped . METHOD Fifty-eight out patients with DSM-IV major depressive episode and prospect ively confirmed nonresponse to fluoxetine ( mean final dose = 31 mg/day ) were switched directly to citalopram ( 20 mg/day ) . Of the 58 patients , 44 ( 76 % ) had never been successfully treated with antidepressant medication . During a 12-week open-label treatment period , citalopram could be titrated up to a maximum dose of 60 mg/day . Response was evaluated using the Clinical Global Impressions ( CGI ) scale , the 24-item Hamilton Rating Scale for Depression , and several other measures . RESULTS Eighty-one percent ( N = 47 ) completed the trial , and citalopram ( mean dose = 38.8 mg/day ) was well tolerated . The intent-to-treat CGI response rate was 46 % ( 26/57 ) at week 6 and 63 % ( 36/57 ) at study endpoint ; the completer response rate was 76 % among the 47 patients who completed the 12-week trial . Improvement from baseline on all dependent measures was statistically significant after the first week of citalopram treatment . CONCLUSION Fluoxetine nonresponders can be quickly switched to citalopram , with good tolerability and reasonable chance of therapeutic benefit . Further work is necessary to assess the merits of this treatment strategy relative to other options BACKGROUND Approximately half of patients who are prescribed selective serotonin re-uptake inhibitors ( SSRIs ) either do not respond to treatment or do not experience a sustained response . OBJECTIVE The purpose of this study was to assess the efficacy of venlafaxine immediate-release ( IR ) and extended-release ( XR ) in out patients who either did not respond to SSRI treatment or did not maintain a sustained response . METHODS Out patients who met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria for major depressive disorder who were previously treated with an SSRI ( fluoxetine > or = 20 mg/d ; sertraline > or = 50 mg/d ; paroxetine > or = 20 mg/d ) for > or = 6 weeks , but demonstrated an inadequate or unsustained response , were switched  to venlafaxine ( IR or XR formulation , 50 - 400 mg/d , titrated from 37.5 mg/d ) for > or = 6 weeks . Response at 6 to 8 weeks was defined as total score < or = 10 on the modified 25-item Hamilton Depression ( HAM-D25 ) rating scale or total score > or = 5 on the 21-item Patient Global Improvement ( PGI-21 ) scale . Remission was defined as a HAM-D25 total score < or = 8 or PGI-21 score > or = 7 . Tests were administered by an unblinded , board-certified psychiatrist . RESULTS A total of 73 patients ( 54 women , 19 men ; mean age , 38.6 years ) were enrolled and treated with venlafaxine IR ( n = 63 ) or venlafaxine XR ( n = 10 ) ; 33 were SSRI nonresponders and 36 had an unsustained response to SSRI treatment . Four patients receiving venlafaxine IR discontinued due to drug-related adverse events ( agitation , sedation , or nausea ) . Data from these patients were excluded from the analysis . After 6 to 8 weeks of treatment , 94.2 % ( 65/69 ) of patients were considered responders ( HAM-D25 or PGI-21 criteria ) ; 91.3 % ( 63/69 ) of patients responded to treatment as assessed by both measures . Eighty-seven percent ( 60/69 ) and 85.5 % ( 59/69 ) of patients achieved remission based on HAM-D,5 and PGI 
    Output:
    