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: Abstract : In this double-blind , multicenter study , bupropion XL , a norepinephrine-dopamine reuptake inhibitor , and venlafaxine XR , a serotonin-norepinephrine reuptake inhibitor , were compared with regard to sexual functioning , efficacy , and tolerability . A total of 348 sexually active adult out patients with depression were r and omized to receive bupropion XL ( titrated to a target dose of 300 - 450 mg/d ) or venlafaxine XR ( titrated to a target dose of 150 - 225 mg/d ) for 12 weeks . Total scores on the primary dependent variable , the Changes in Sexual Functioning Question naire ( self-report ) , increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR ; the mean change scores differed significantly between groups from week 2 onward . Among subjects with normal pretreatment sexual functioning , Changes in Sexual Functioning Question naire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group ; mean change scores also differed between groups from week 2 onward . Although the therapies result ed in similar change on the 17-item Hamilton Depression Rating Scale , remission rates were significantly higher among those treated with bupropion XL ( 46 % ) versus venlafaxine XR ( 33 % ) ( odds ratio , 1.93 ; 95 % confidence interval , 1.07 - 3.46 ) . Aside from adverse effects of venlafaxine XR on sexual function , both treatments were reasonably well tolerated . In conclusion , in this patient population ( ie , relatively young , sexually active out patients ) , bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile Trazodone Contramid(R ) once-a-day ( TzCOAD ) is a reformulation of trazodone hydrochloride that controls the release of trazodone over 24 hours . A st and ard effect size analysis ( Cohen 's d ) determined which items of the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and the Montgomery-Asberg Depression Rating Scale ( MADRS ) showed the greatest improvement in patients with major depressive disorder ( MDD ) , following up to 8 weeks of therapy with TzCOAD . An additional insomnia analysis assessed whether the efficacy of TzCOAD is influenced by improvements in insomnia or baseline severity of insomnia . The analyses used data from a r and omized study of 412 patients receiving 150 - 375 mg TzCOAD ( N = 206 ) or placebo ( N = 206 ) . The results of the Cohen 's d analysis on the modified intent-to-treat population ( LOCF ) showed HAMD items with the greatest improvement were insomnia items ( middle ( -0.35 ) , late ( -0.24 ) ) , feelings of guilt ( -0.24 ) , and depressed mood ( -0.23 ) ; for MADRS items they were reduced sleep ( -0.31 ) , inner tension ( -0.22 ) , reported sadness ( -0.21 ) , and suicidal thoughts ( -0.21 ) . An analysis of covariance showed no significant interaction between improvements in the HAMD Bech-6 core symptoms of depression and the baseline MADRS reduced sleep item or early changes in the HAMD-17 sleep disturbance factor . These results suggest that the antidepressant efficacy was independent of the baseline severity of insomnia and of the improvement in insomnia . Overall , the results eluci date the efficacy components and tolerability characteristics previously demonstrated for TzCOAD monotherapy for patients with MDD at the recommended daily dose of 300 mg Antidepressant effects and unintended effects of paroxetine ( 30 mg/day ) and clomipramine ( 150 mg/day ) were compared in a double-blind , r and omized , inpatient , fixed-dose , plasma-level-controlled study . Patients with a DSM-III diagnosis of major depressive disorder participated . After 1 week of single-blind placebo treatment  120 patients fulfilled the criterion of a Hamilton ( 17-item ) score of greater than or equal to 18 and were started on active treatment for 6 weeks . Drop-outs on paroxetine ( n = 12 ) were largely due to lack of effect , and on clomipramine ( n = 19 ) due to lack of effect ( n = 7 ) , adverse reactions or severe side effects ( n = 10 ) and development of mania ( n = 2 ) . According to the protocol , non-responders ( Hamilton total greater than or equal to 16 ) after 4 weeks active treatment were terminated , and this occurred to 23 patients on paroxetine and four patients on clomipramine . Categorical response measures and group averages of rating scores showed a significantly better therapeutic effect of clomipramine from the second week of treatment on . These results are very similar to our earlier results with another selective serotonin reuptake inhibitor ( citalopram ) , but generally at variance with the literature on this class of antidepressants , which , however , mostly deals with outpatient studies In a 6-week double-blind study , 220 patients with major depression ( mostly out patients ) were r and omly assigned to receive a fixed dose of brofaromine 150 mg daily ( n = 111 ) or placebo ( n = 109 ) after a 1-week single-blind placebo washout . Except for the HAM-D sleep items , brofaromine was superior to placebo on measures of depression as determined by the four methods of assessing drug efficacy : ( 1 ) psychiatric symptom rating ( HAM-D 17-item less the three sleep items ) ; ( 2 ) self-rating scale ( Beck Depression Inventory ) ; ( 3 ) Clinical Global Assessment of Efficacy ; and ( 4 ) drop-out rate due to lack of efficacy . Most commonly reported adverse events with brofaromine were : headache , nausea , dizziness and sleep disturbance .  Brofaromine was found to be an effective antidepressant , superior to placebo with a good tolerability profile In depression research , symptoms are routinely assessed via rating scales and added to construct sum-scores . These scores are used as a proxy for depression severity in cross-sectional research , and differences in sum-scores over time are taken to reflect changes in an underlying depression construct . To allow for such interpretations , rating scales must ( a ) measure a single construct , and ( b ) measure that construct in the same way across time . These requirements are referred to as unidimensionality and measurement invariance . We investigated these 2 requirements in 2 large prospect i ve studies ( combined n = 3,509 ) in which overall depression levels decrease , examining 4 common depression rating scales ( 1 self-report , 3 clinician-report ) with different time intervals between assessment s ( between 6 weeks and 2 years ) . A consistent pattern of results emerged . For all instruments , neither unidimensionality nor measurement invariance appeared remotely tenable . At least 3 factors were required to describe each scale , and the factor structure changed over time . Typically , the structure became less multifactorial as depression severity decreased ( without however reaching unidimensionality ) . The decrease in the sum-scores was accompanied by an increase in the variances of the sum-scores , and increases in internal consistency . These findings challenge the common interpretation of sum-scores and their changes as reflecting 1 underlying construct . The violations of common measurement requirements are sufficiently severe to suggest alternative interpretations of depression sum-scores as formative instead of reflective measures . We discuss the possible causes of these violations such as response shift bias , restriction of range , and regression to the mean . ( PsycINFO Data base The consistency of the Hamilton Depression Scale  ( HDS ) as a measure of the severity of depressive states has been examined when the scale was used weekly during a trial with imipramine . By use of logistic models ( Rasch ) the consistency of the HDS has been considered across patient‐variables as age , sex , plasma levels of imipramine , and diagnosis . The results showed that the original 17‐item HDS was without adequate consistency , i.e. the total score of the sample of items was no one‐dimensional measure of depressive states . However , a melancholia subscale of the HDS contained items the total of which can be used to compare patients quantitatively , although in some part of the analysis one of these items showed ceiling effect . It was concluded that the melancholia sub‐scale ( containing the items depressed mood , guilt , work and interests , retardation , psychic anxiety , and general somatic symptoms ) can form the basis for further improvements in the field of quantitative rating scales for depressive states Background This paper reports day-to-day data for from a one-week intervention phase , part of a 9-weeks r and omised parallel study with patient having major depression ( data from weekly visits have been reported ) . Wake therapy ( sleep deprivation ) has an established antidepressant effect with onset of action within hours . Deterioration on the following night ’s sleep is , however , common , and we used daily light therapy and sleep time stabilisation as a preventive measure . In particular , we evaluated the day-to-day acute effect of and tolerance to sleep deprivation and examined predictors of response . Methods Patients were assessed at psychiatric inpatient wards . In the wake group ( n = 36 ) , patients did three wake therapies in combination with light therapy each morning together with sleep time stabilisation . In the exercise group ( n = 38 ) , patients did daily exercise .  Hamilton subscale scores were primary outcome ( not blinded ) , secondary outcome was self- assessment data from the Preskorn scale and sleep . Results Patients in the wake therapy group had an immediate , large , stable , and statistically significant better antidepressant effect than patients in the exercise group with response rates at day5 of 75.0%/25.1 % and remission rates of 58.6%/6.0 % , respectively . The response and remission rates were diminished at day8 with response rates of 41.9%/10.1 % and remission rates of 19.4%/4.7 % , respectively . Patients and ward personnel found the method applicable with few side effects . Positive diurnal variation ( mood better in the evening ) predicted a larger response to wake therapy . In the wake group napping on days after intervention predicted greater deterioration on day8 . Conclusions The intervention induced an acute antidepressant response without relapse between wake nights but with a diminishing effect after intervention . Development is still needed to secure maintenance of response . Avoiding napping in the days after wake therapy is important . Trial Registration Clinical trials.gov A total of 97 patients , who participated in two studies on the relationship between the clinical effect and plasma levels of imipramine and clomipramine  , were examined for improvement curves by use of weekly ratings on the Hamilton Depression Scale ( HDS ) . Although we confirmed that our six-item HDS subscale , in contrast to the total 17-item HDS , was a one-dimensional measure of depression , the Rasch analysis showed that the weekly improvement in subscale scores only applied to the individual patient , i.e. an average improvement curve for a group of depressed patients is an abstract ion to which the individual curves can not be transferred . Our results indicate , however , that when the subscale scores are transformed into three clinical categories of depression : no , mild ( minor ) , moderate/-severe ( major ) they could be described by a common improvement curve for all patients . This is illustrated by the percentage of patients who , week to week , changed from major to minor or no depression , or from minor to no depression . We found no specific improvement pattern for imipramine or clomipramine which could be used diagnostically . There is reason to assume that patients completing a controlled trial necessarily will follow a monotonic improvement curve , and the improvement pattern of all patients fulfilling the entry criteria should , therefore , always be reported . The present study thus indicates that calculation of average improvement curves is neither clinical ly nor statistically meaningful , and should be replaced by measures of changes in number of patients in different main severity categories , or by the final rating score . No difference in outcome between imipramine and clomipramine was shown neither on the subscale nor on the 17-item HDS BACKGROUND The 17-item  Hamilton Depression Rating Scale  ( HDRS ) is used as a semi-gold st and ard in research . In treatment guidelines , the HDRS measurements serve to determine response and remission and guide clinical decision making for nonresponders . However , its use in clinical practice is limited , possibly because the HDRS is time consuming . In addition , the multidimensional HDRS is criticized for not measuring a unidimensional aspect as depression severity . The Maier and the Bech , two 6-item severity subscales extracted from the HDRS , are relatively unknown . This paper investigates whether the measurements obtained with these subscales are comparable with the original HDRS measurements . METHODS Data from 2 r and omized controlled trials in 482 male and female patients , diagnosed with a major depression ( with or without dysthymia ) according to Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition , of whom 219 participated in the trials , were reanalyzed . A st and ardized stepwise psychopharmacological treatment was compared with a combination of pharmacotherapy with Short Psychodynamic Supportive Psychotherapy in a psychiatric outpatient department . Outcome measures were internal consistency and concurrent validity of HDRS , Maier , Bech , Clinical Global Impression scales , and Symptom Checklist depression subscale . Effect sizes of HDRS , Maier , and Bech were used to compare measured treatment effects for the r and omized subjects participating in the trials . Item Response Theory was used to obtain conversion tables for the HDRS , Maier , Bech , and Symptom Checklist depression subscale . RES 
    Output:
    
agent
Conclusions : According to the published literature , the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS .
***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: Abstract : In this double-blind , multicenter study , bupropion XL , a norepinephrine-dopamine reuptake inhibitor , and venlafaxine XR , a serotonin-norepinephrine reuptake inhibitor , were compared with regard to sexual functioning , efficacy , and tolerability . A total of 348 sexually active adult out patients with depression were r and omized to receive bupropion XL ( titrated to a target dose of 300 - 450 mg/d ) or venlafaxine XR ( titrated to a target dose of 150 - 225 mg/d ) for 12 weeks . Total scores on the primary dependent variable , the Changes in Sexual Functioning Question naire ( self-report ) , increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR ; the mean change scores differed significantly between groups from week 2 onward . Among subjects with normal pretreatment sexual functioning , Changes in Sexual Functioning Question naire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group ; mean change scores also differed between groups from week 2 onward . Although the therapies result ed in similar change on the 17-item Hamilton Depression Rating Scale , remission rates were significantly higher among those treated with bupropion XL ( 46 % ) versus venlafaxine XR ( 33 % ) ( odds ratio , 1.93 ; 95 % confidence interval , 1.07 - 3.46 ) . Aside from adverse effects of venlafaxine XR on sexual function , both treatments were reasonably well tolerated . In conclusion , in this patient population ( ie , relatively young , sexually active out patients ) , bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile Trazodone Contramid(R ) once-a-day ( TzCOAD ) is a reformulation of trazodone hydrochloride that controls the release of trazodone over 24 hours . A st and ard effect size analysis ( Cohen 's d ) determined which items of the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and the Montgomery-Asberg Depression Rating Scale ( MADRS ) showed the greatest improvement in patients with major depressive disorder ( MDD ) , following up to 8 weeks of therapy with TzCOAD . An additional insomnia analysis assessed whether the efficacy of TzCOAD is influenced by improvements in insomnia or baseline severity of insomnia . The analyses used data from a r and omized study of 412 patients receiving 150 - 375 mg TzCOAD ( N = 206 ) or placebo ( N = 206 ) . The results of the Cohen 's d analysis on the modified intent-to-treat population ( LOCF ) showed HAMD items with the greatest improvement were insomnia items ( middle ( -0.35 ) , late ( -0.24 ) ) , feelings of guilt ( -0.24 ) , and depressed mood ( -0.23 ) ; for MADRS items they were reduced sleep ( -0.31 ) , inner tension ( -0.22 ) , reported sadness ( -0.21 ) , and suicidal thoughts ( -0.21 ) . An analysis of covariance showed no significant interaction between improvements in the HAMD Bech-6 core symptoms of depression and the baseline MADRS reduced sleep item or early changes in the HAMD-17 sleep disturbance factor . These results suggest that the antidepressant efficacy was independent of the baseline severity of insomnia and of the improvement in insomnia . Overall , the results eluci date the efficacy components and tolerability characteristics previously demonstrated for TzCOAD monotherapy for patients with MDD at the recommended daily dose of 300 mg Antidepressant effects and unintended effects of paroxetine ( 30 mg/day ) and clomipramine ( 150 mg/day ) were compared in a double-blind , r and omized , inpatient , fixed-dose , plasma-level-controlled study . Patients with a DSM-III diagnosis of major depressive disorder participated . After 1 week of single-blind placebo treatment  120 patients fulfilled the criterion of a Hamilton ( 17-item ) score of greater than or equal to 18 and were started on active treatment for 6 weeks . Drop-outs on paroxetine ( n = 12 ) were largely due to lack of effect , and on clomipramine ( n = 19 ) due to lack of effect ( n = 7 ) , adverse reactions or severe side effects ( n = 10 ) and development of mania ( n = 2 ) . According to the protocol , non-responders ( Hamilton total greater than or equal to 16 ) after 4 weeks active treatment were terminated , and this occurred to 23 patients on paroxetine and four patients on clomipramine . Categorical response measures and group averages of rating scores showed a significantly better therapeutic effect of clomipramine from the second week of treatment on . These results are very similar to our earlier results with another selective serotonin reuptake inhibitor ( citalopram ) , but generally at variance with the literature on this class of antidepressants , which , however , mostly deals with outpatient studies In a 6-week double-blind study , 220 patients with major depression ( mostly out patients ) were r and omly assigned to receive a fixed dose of brofaromine 150 mg daily ( n = 111 ) or placebo ( n = 109 ) after a 1-week single-blind placebo washout . Except for the HAM-D sleep items , brofaromine was superior to placebo on measures of depression as determined by the four methods of assessing drug efficacy : ( 1 ) psychiatric symptom rating ( HAM-D 17-item less the three sleep items ) ; ( 2 ) self-rating scale ( Beck Depression Inventory ) ; ( 3 ) Clinical Global Assessment of Efficacy ; and ( 4 ) drop-out rate due to lack of efficacy . Most commonly reported adverse events with brofaromine were : headache , nausea , dizziness and sleep disturbance .  Brofaromine was found to be an effective antidepressant , superior to placebo with a good tolerability profile In depression research , symptoms are routinely assessed via rating scales and added to construct sum-scores . These scores are used as a proxy for depression severity in cross-sectional research , and differences in sum-scores over time are taken to reflect changes in an underlying depression construct . To allow for such interpretations , rating scales must ( a ) measure a single construct , and ( b ) measure that construct in the same way across time . These requirements are referred to as unidimensionality and measurement invariance . We investigated these 2 requirements in 2 large prospect i ve studies ( combined n = 3,509 ) in which overall depression levels decrease , examining 4 common depression rating scales ( 1 self-report , 3 clinician-report ) with different time intervals between assessment s ( between 6 weeks and 2 years ) . A consistent pattern of results emerged . For all instruments , neither unidimensionality nor measurement invariance appeared remotely tenable . At least 3 factors were required to describe each scale , and the factor structure changed over time . Typically , the structure became less multifactorial as depression severity decreased ( without however reaching unidimensionality ) . The decrease in the sum-scores was accompanied by an increase in the variances of the sum-scores , and increases in internal consistency . These findings challenge the common interpretation of sum-scores and their changes as reflecting 1 underlying construct . The violations of common measurement requirements are sufficiently severe to suggest alternative interpretations of depression sum-scores as formative instead of reflective measures . We discuss the possible causes of these violations such as response shift bias , restriction of range , and regression to the mean . ( PsycINFO Data base The consistency of the Hamilton Depression Scale  ( HDS ) as a measure of the severity of depressive states has been examined when the scale was used weekly during a trial with imipramine . By use of logistic models ( Rasch ) the consistency of the HDS has been considered across patient‐variables as age , sex , plasma levels of imipramine , and diagnosis . The results showed that the original 17‐item HDS was without adequate consistency , i.e. the total score of the sample of items was no one‐dimensional measure of depressive states . However , a melancholia subscale of the HDS contained items the total of which can be used to compare patients quantitatively , although in some part of the analysis one of these items showed ceiling effect . It was concluded that the melancholia sub‐scale ( containing the items depressed mood , guilt , work and interests , retardation , psychic anxiety , and general somatic symptoms ) can form the basis for further improvements in the field of quantitative rating scales for depressive states Background This paper reports day-to-day data for from a one-week intervention phase , part of a 9-weeks r and omised parallel study with patient having major depression ( data from weekly visits have been reported ) . Wake therapy ( sleep deprivation ) has an established antidepressant effect with onset of action within hours . Deterioration on the following night ’s sleep is , however , common , and we used daily light therapy and sleep time stabilisation as a preventive measure . In particular , we evaluated the day-to-day acute effect of and tolerance to sleep deprivation and examined predictors of response . Methods Patients were assessed at psychiatric inpatient wards . In the wake group ( n = 36 ) , patients did three wake therapies in combination with light therapy each morning together with sleep time stabilisation . In the exercise group ( n = 38 ) , patients did daily exercise .  Hamilton subscale scores were primary outcome ( not blinded ) , secondary outcome was self- assessment data from the Preskorn scale and sleep . Results Patients in the wake therapy group had an immediate , large , stable , and statistically significant better antidepressant effect than patients in the exercise group with response rates at day5 of 75.0%/25.1 % and remission rates of 58.6%/6.0 % , respectively . The response and remission rates were diminished at day8 with response rates of 41.9%/10.1 % and remission rates of 19.4%/4.7 % , respectively . Patients and ward personnel found the method applicable with few side effects . Positive diurnal variation ( mood better in the evening ) predicted a larger response to wake therapy . In the wake group napping on days after intervention predicted greater deterioration on day8 . Conclusions The intervention induced an acute antidepressant response without relapse between wake nights but with a diminishing effect after intervention . Development is still needed to secure maintenance of response . Avoiding napping in the days after wake therapy is important . Trial Registration Clinical trials.gov A total of 97 patients , who participated in two studies on the relationship between the clinical effect and plasma levels of imipramine and clomipramine  , were examined for improvement curves by use of weekly ratings on the Hamilton Depression Scale ( HDS ) . Although we confirmed that our six-item HDS subscale , in contrast to the total 17-item HDS , was a one-dimensional measure of depression , the Rasch analysis showed that the weekly improvement in subscale scores only applied to the individual patient , i.e. an average improvement curve for a group of depressed patients is an abstract ion to which the individual curves can not be transferred . Our results indicate , however , that when the subscale scores are transformed into three clinical categories of depression : no , mild ( minor ) , moderate/-severe ( major ) they could be described by a common improvement curve for all patients . This is illustrated by the percentage of patients who , week to week , changed from major to minor or no depression , or from minor to no depression . We found no specific improvement pattern for imipramine or clomipramine which could be used diagnostically . There is reason to assume that patients completing a controlled trial necessarily will follow a monotonic improvement curve , and the improvement pattern of all patients fulfilling the entry criteria should , therefore , always be reported . The present study thus indicates that calculation of average improvement curves is neither clinical ly nor statistically meaningful , and should be replaced by measures of changes in number of patients in different main severity categories , or by the final rating score . No difference in outcome between imipramine and clomipramine was shown neither on the subscale nor on the 17-item HDS BACKGROUND The 17-item  Hamilton Depression Rating Scale  ( HDRS ) is used as a semi-gold st and ard in research . In treatment guidelines , the HDRS measurements serve to determine response and remission and guide clinical decision making for nonresponders . However , its use in clinical practice is limited , possibly because the HDRS is time consuming . In addition , the multidimensional HDRS is criticized for not measuring a unidimensional aspect as depression severity . The Maier and the Bech , two 6-item severity subscales extracted from the HDRS , are relatively unknown . This paper investigates whether the measurements obtained with these subscales are comparable with the original HDRS measurements . METHODS Data from 2 r and omized controlled trials in 482 male and female patients , diagnosed with a major depression ( with or without dysthymia ) according to Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition , of whom 219 participated in the trials , were reanalyzed . A st and ardized stepwise psychopharmacological treatment was compared with a combination of pharmacotherapy with Short Psychodynamic Supportive Psychotherapy in a psychiatric outpatient department . Outcome measures were internal consistency and concurrent validity of HDRS , Maier , Bech , Clinical Global Impression scales , and Symptom Checklist depression subscale . Effect sizes of HDRS , Maier , and Bech were used to compare measured treatment effects for the r and omized subjects participating in the trials . Item Response Theory was used to obtain conversion tables for the HDRS , Maier , Bech , and Symptom Checklist depression subscale . RES 
    Output:
    