title: A Double-blind Comparison Between Bupropion XL and Venlafaxine XR: Sexual Functioning, Antidepressant Efficacy, and Tolerability The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder. Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group. A Canadian multicentre placebo-controlled study of a fixed dose of brofaromine, a reversible selective MAO-A inhibitor, in the treatment of major depression. Measuring depression over time . . . Or not? Lack of unidimensionality and longitudinal measurement invariance in four common rating scales of depression. The Hamilton Depression Scale The Day-to-Day Acute Effect of Wake Therapy in Patients with Major Depression Using the HAM-D6 as Primary Outcome Measure: Results from a Randomised Controlled Trial Assessment of symptom change from improvement curves on the Hamilton depression scale in trials with antidepressants Clinical use of the Hamilton Depression Rating Scale: is increased efficiency possible? A post hoc comparison of Hamilton Depression Rating Scale, Maier and Bech subscales, Clinical Global Impression, and Symptom Checklist-90 scores. The Montgomery Äsberg and the Hamilton ratings of depression: A comparison of measures The nature of placebo response in clinical studies of major depressive disorder. Diagnostic conversion to bipolar disorder in unipolar depressed patients participating in trials on antidepressants. Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression A double-blind trial of low- and high-dose ranges of gepirone-ER compared with placebo in the treatment of depressed outpatients. Establishing the cut-off score for remission and severity-ranges on the Psychotic Depression Assessment Scale (PDAS). A double-blind comparison of gepirone extended release, imipramine, and placebo in the treatment of outpatient major depression. Results From 2 Randomized, Double-Blind, Placebo-Controlled Studies of the Novel NK1 Receptor Antagonist Casopitant in Patients With Major Depressive Disorder An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Gepirone extended-release: new evidence for efficacy in the treatment of major depressive disorder. Sertraline safety and efficacy in major depression: A double-blind fixed-dose comparison with placebo Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Mirtazapine is more effective than trazodone: a double‐blind controlled study in hospitalized patients with major depression Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo‐controlled study A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. Adjunctive bright light in non‐seasonal major depression: results from clinician‐rated depression scales Remission with venlafaxine extended release or selective serotonin reuptake inhibitors in depressed patients: a randomized, open-label study. Selegiline transdermal system for the treatment of major depressive disorder: an 8-week, double-blind, placebo-controlled, flexible-dose titration trial. An examination of the sensitivity of the six-item Hamilton Rating Scale for Depression in a sample of patients suffering from major depressive disorder. The responsiveness of the different versions of the Hamilton Depression Scale. Is the antidepressive effect of second-generation antidepressants a myth? HAM-D17 and HAM-D6 sensitivity to change in relation to desvenlafaxine dose and baseline depression severity in major depressive disorder.
abstract: 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 . RESULTS We found moderate internal consistency ( Cronbach alpha approximately 0.6 - 0.7 ) and high correlations of the Maier and Bech subscales with overall HDRS scores . Overall , there were no clinical ly relevant differences in effect sizes between Maier , Bech , and HDRS , although some differences were statistically significant . Receiver operating characteristic curves showed no difference between Maier and Bech to define remission but showed the Clinical Global Impression ratings to be unreliable . A cutoff < or = 4 corresponded with an HDRS < or = 7 criterion in both subscales . CONCLUSION In clinical practice , both Maier and Bech scales can be used as equivalents of the HDRS , but will be more efficient The 17-item Hamilton Rating Scale for Depression  ( HRSD(17 ) ) and the Montgomery Asberg Depression Rating Scale ( MADRS ) are two widely used clinician-rated symptom scales . A 6-item version of the HRSD ( HRSD(6 ) ) was created by Bech to address the psychometric limitations of the HRSD(17 ) . The psychometric properties of these measures were compared using classical test theory ( CTT ) and item response theory ( IRT ) methods . IRT methods were used to equate total scores on any two scales . Data from two distinctly different outpatient studies of nonpsychotic major depression : a 12-month study of highly treatment-resistant patients ( n=233 ) and an 8-week acute phase drug treatment trial ( n=985 ) were used for robustness of results . MADRS and HRSD(6 ) items generally contributed more to the measurement of depression than HRSD(17 ) items as shown by higher item-total correlations and higher IRT slope parameters . The MADRS and HRSD(6 ) were unifactorial while the HRSD(17 ) contained 2 factors . The MADRS showed about twice the precision in estimating depression as either the HRSD(17 ) or HRSD(6 ) for average severity of depression . An HRSD(17 ) of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD(6 ) . The MADRS would be superior to the HRSD(17 ) in the conduct of clinical trials OBJECTIVE To review factors influencing placebo response and clinical trial outcome in depression , and suggest ways to optimize trial success in mood disorders . DATA SOURCES PubMed search es were conducted by cross-referencing the terms depression , depressive with placebo , clinical trial , and clinical trials for studies published in English between 1970 and September 2013 . STUDY SELECTION Relevant abstract s were identified in PubMed , including clinical trials , quantitative studies , and qualitative research . We obtained and review ed relevant articles and utilized their information to synthesize the present review . DATA EXTRACTION Included articles were grouped in the following areas of relevance : ( 1 ) biological validity of illness , ( 2 ) baseline severity of illness , ( 3 ) chronicity of the index episode of depression , ( 4 ) age of participants , ( 5 ) medical and psychiatric comorbidity , ( 6 ) probability of receiving placebo , ( 7 ) use of prospect i ve treatment phases ( lead-in ) ( 8) dosing schedule , ( 9 ) trial duration , ( 10 ) frequency of follow-up assessment s , and ( 11 ) study outcome measure . RESULTS Several key elements emerge as critical to the ultimate success of a clinical trial , including the probability of receiving placebo , study duration , dosing schedule , visit frequency , the use of blinded lead-in phases , the use of central ized raters , illness severity and duration , and comorbid anxiety . CONCLUSIONS Our increasing underst and ing of the placebo response in clinical trials of major depressive disorder lends to a , gradually , more predictable phenomenon and , hopefully , to one that becomes lesser in magnitude and variability . Several elements have emerged that seem to play a critical role in trial success , gradually reshaping the design of clinical , translational , as well as mechanistic studies in depression OBJECTIVE In unipolar depressed patients participating in trials on antidepressants , we investigated if illness characteristics at baseline could predict conversion to bipolar disorder . METHOD A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years ( SD=11.9 ) participating in three r and omized trials on antidepressants conducted in the period 1985 - 1994 . The independent effects of explanatory variables were examined by applying Cox regression analyses . RESULTS The overall risk of conversion was 20.7 % , with a mean follow-up time of 15.2 years per patient . The risk of conversion was associated with an increasing number of previous depressive episodes at baseline , [ HR 1.18 , 95 % CI ( 1.10 - 1.26 ) ] . No association with gender , age , age at first depressive episode , duration of baseline episode , subtype of depression or any of the investigated HAM-D subscales included was found . LIMITATIONS The patients were followed-up through the Danish Psychiatric Central Research Register , which result ed in inherent limitations such as possible misclassification of outcome . CONCLUSION In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants , the risk of conversion was associated with the number of previous depressive episodes . Therefore , this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely , or at least be informed about the possible increased risk of conversion In the efficacy evaluation of antidepressant treatments , the total score of the Hamilton Depression Rating Scale ( HAMD ) is still regarded as the ‘ gold st and ard ’ . We previously had shown that the Inventory of Depressive Symptomatology ( IDS ) was more sensitive to detect depressive symptom changes than the HAMD17 ( Helmreich et al. 2011 ) . Furthermore , studies suggest that the unidimensional subscales of the HAMD , which capture the core depressive symptoms , outperform the full HAMD regarding the detection of antidepressant treatment effects . The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major , minor or subsyndromal depression ( MIND ) . Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week r and omised , placebo-controlled trial comparing the effectiveness of sertraline and cognitive – behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course . We investigated sensitivity to depressive change for all scales from assessment -to- assessment , in relation to depression severity level and placebo – verum differences . The subscales performed similarly during the treatment course , with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included . Most changes in depressive symptomatology were detected by the IDS short scale , but regarding the effect sizes , it performed worse than most subscales . Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes , especially in antidepressant treatment efficacy studies . However , subscales do not cover all facets of depression ( e.g. atypical symptoms , sleep disturbances ) , which might be important for comprehensively underst and ing the nature of the disease depression . Therefore , the cost-to-benefit ratio must be carefully assessed in the decision for using unidimensional subscales We report the results of a double-blind study comparing the efficacy and safety of low-dose ( 10 - 50 mg ) and high-dose ( 20 - 100 mg ) ranges of gepirone-extended release ( ER ) and placebo in 145 out patients with major depressive disorder . At multiple time points and endpoint ( Week 6 ) , statistically significant reductions in Hamilton Rating Scale for Depression ( HAM-D ) scores were recorded for high-dose gepirone-ER compared to placebo . Analysis of the 17-item HAM-D and 28-item HAM-D scores indicated a relatively early onset of antidepressant efficacy with statistically significant results at treatment Weeks 1 , 2 , 4 , and 6 . A rapid response was evident in the high-dose group , beginning at Week 1 ( p < .05 ) . The most frequently reported adverse experiences were headache , nausea , dizziness , and insomnia . The results indicate that gepirone-ER is clearly superior to placebo in terms of antidepressant efficacy . When used at higher doses , gepirone-ER appears to be efficacious , safe , and well-tolerated in depressed out- patients BACKGROUND The Psychotic Depression Assessment Scale ( PDAS ) is a rating scale dedicated to the measurement of severity in psychotic depression ( PD ) . The aim of this study was to establish the PDAS cut-off for remission of PD as well as PDAS score-ranges for mild , moderate , and severe PD . The secondary aim was to test how remission , as defined by the PDAS , would perform as outcome measure when applied to the data from a large r and omized controlled trial ( RCT ) in PD . METHODS The study was based on data from the Study of Pharmacotherapy in Psychotic Depression ( STOP-PD ) . The cut-off for remission on the PDAS and the severity-ranges for mild , moderate , and severe PD were defined using the Clinical Global Impression - Severity scale ( CGI-S ) as reference by means of pair-wise receiver operating characteristic ( ROC ) analyses . Subsequently , it was tested whether remission on the PDAS could separate the effects of Olanzapine+Sertraline vs. Olanzapine+Placebo through an intention-to-treat , mixed-effects logistic regression of the data from STOP-PD . RESULTS According to the ROC analyses , the ideal cut-off for remission of PD was a PDAS total score < 8 , while the severity-ranges for mild , moderate and severe PD were 8 - 15 , 16 - 23 , and > 23 respectively . When applying the PDAS total score < 8 ( remission ) as outcome on the STOP-PD data , treatment with Olanzapine+Sertraline performed significantly better than Olanzapine+Placebo ( p<0.001 ) . LIMITATIONS The STOP-PD was not design ed specifically to answer the research questions of the present study . CONCLUSIONS According to this study , a total score < 8 on the PDAS corresponds to remission of PD We report the results from one site of a two-site , double-blind , placebo-controlled comparison study of gepirone extended release ( ER ) and imipramine in the management of major depression . In the study , 123 subjects with DSM-III-R major depression were r and omized to 8 weeks of treatment with gepirone ER ( 10 - 60 mg/day ) , imipramine ( 50 - 300 mg/day ) , or placebo . According to last observation carried forward ( LOCF ) analyses of 120 intent-to-treat subjects , both gepirone ER and imipramine were superior to placebo at Weeks 6 and 8 on the Hamilton Rating Scale for Depression 17- and 28-item ( HAM-D-17 and HAM-D-28 ) instruments , the Clinical Global Impressions ( CGI ) Severity of illness scale , and the total Bech Six-Item Core Depression Cluster score .  Gepirone ER was better tolerated than imipramine when judged by dropout rates for adverse events Clinical study results for neurokinin ( NK ) receptor antagonists in the treatment of depression have been mixed , with Phase III studies failing to fulfill the early promise demonstrated in Phase II studies . Casopitant , a selective NK1 antagonist that achieves nearly complete receptor occupancy was studied in 2 r and omized , placebo-controlled , double-blind , Phase II trials in depressed out patients to test the hypothesis that nearly complete NK1 receptor occupancy is required to achieve antidepressant efficacy . Study 092 used an interactive voice response system to recruit depressed patients with baseline Hamilton Depression ( 17-item , HAMD17 ) total scores higher than 24 who were r and omized to fixed-dose casopitant 30 mg/d , 80 mg/d , or placebo for 8 weeks ( n = 356 ) . Study 096 required Carroll Depression Scale-Revised self- assessment scores of higher than 24 for r and omization to casopitant 120 mg/d , paroxetine 30 mg/d ( both reached via forced titration ) , or placebo for 8 weeks ( n = 362 ) . In study 092 , casopitant 80 mg but not 30 mg achieved statistically significant improvement versus placebo on the primary outcome measure , week 8 last observation carried forward change from baseline HAMD17 ( difference = −2.7 ; 95 % confidence interval , −5.1 to −0.4 , P = 0.023 ) . In study 096 , neither casopitant nor paroxetine achieved statistical separation from placebo at end point on HAMD17 ( casopitant difference = −1.7 ; 95 % CI , −3.8 to 0.4 , P = 0.282 ) . Casopitant and paroxetine were generally well tolerated in most patients . These studies suggest that NK1 antagonists that have nearly complete receptor occupancy may be effective in the treatment of depression 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 OBJECTIVE To assess the efficacy and tolerability of the 5-HT(1A ) agonist gepirone in extended-release formulation ( gepirone-ER ) versus placebo in patients with major depressive disorder . METHOD Patients aged 18 to 70 years were eligible if they satisfied DSM-IV criteria for moderate-to-severe major depressive disorder and had a baseline 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) score > or = 20 . After a 4- to 7-day placebo washout period , patients were r and omly assigned to receive either placebo ( N = 106 ) or gepirone-ER ( 20 - 80 mg/day ) ( N = 103 ) for 56 days . Assessment s were done at weeks 1 - 4 , 6 , and 8 . RESULTS Mean change from baseline in HAM-D-17 score within the intent-to-treat group ( gepirone , N = 101 ; placebo , N = 103 ) was significantly greater with gepirone-ER than placebo at weeks 3 ( p = .013 ) and 8 ( p = .018 ) . Significantly ( p < .05 ) more patients receiving gepirone-ER than placebo were HAM-D-17 responders at weeks 3 ( 33.7 % vs. 18.8 % , respectively ) and 4 ( 38.6 % vs. 24.8 % , respectively ) and HAM-D-17 remitters at weeks 6 ( 24.8 % vs. 13.9 % , respectively ) and 8 ( 28.7 % vs. 14.9 % , respectively ) . Mean change from baseline for HAM-D-25 total score was significantly ( p < pr = .05 ) greater with gepirone-ER at all assessment s except week 6 . The proportion of HAM-D-25 responders was significantly greater ( p < or = .05 ) with gepirone-ER at weeks 3 and 8 . Gepirone-ER was well tolerated : 9.8 % of the gepirone-ER group and 2.8 % of the placebo group discontinued due to adverse events . Common adverse events were considered mild and included dizziness , nausea , and insomnia .  Gepirone-ER did not differ statistically compared with placebo in weight gain or sedation . Furthermore , preliminary evidence suggested that gepirone-ER may not be associated with sexual dysfunction . No serious adverse events occurred in gepirone-treated patients . CONCLUSION Gepirone-ER is effective for the short-term treatment of major depressive disorder and is well tolerated In a 6-week , r and omized , double-blind , multicenter trial , sertraline 50 mg , 100 mg , or 200 mg , or placebo , was administered once daily to 369 patients with DSM-III-defined major depression . Efficacy variables included changes from baseline scores for total Hamilton Rating Scale for Depression ( HAMD ) , HAMD Bech Depression Cluster , Clinical Global Impressions ( CGI ) Severity , CGI Improvement , and Profile of Mood States Depression/Dejection Factor . For the evaluable- patients analysis , all sertraline groups showed significantly ( p < 0.05 or better ) greater improvements in all efficacy variables except one when compared with the placebo group . For the all- patients analysis , all efficacy variables in the 50 mg group were statistically significantly ( p < 0.05 ) better than placebo .  Side effects increased with increasing dosage but were usually mild and well tolerated . The results of this study show that sertraline 50 mg once daily is as effective as higher dosages for the treatment of major depression with fewer side effects and therapy discontinuations Two hundred forty-one out patients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam , diazepam , imipramine hydrochloride , and placebo .  Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo . Imipramine-treated patients reported the most and placebo patients the least number of adverse effects .  Imipramine and alprazolam , but not diazepam , produced significantly more improvement in depressed symptomatology than did placebo . Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo . These treatment differences were found to be independent of initial severity levels of anxiety and depression Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability Objective : We have tested the relapse‐preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder ( SAD ) responding to 1 week of light therapy OBJECTIVE This study evaluated the efficacy and tolerability of desvenlafaxine succinate ( desvenlafaxine ) in the treatment of major depressive disorder ( MDD ) . METHOD In this 8-week , multicenter , r and omized , double-blind , placebo-controlled trial , adult out patients ( aged 18 - 75 years ) with a primary diagnosis of MDD ( DSM-IV criteria ) were r and omly assigned to treatment with desvenlafaxine ( 100 - 200 mg/day ) or placebo . The primary outcome measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D(17 ) ) score at final on-therapy evaluation . The Clinical Global Impressions-Improvement scale ( CGI-I ) was the key secondary measure . Other secondary measures included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions-Severity of Illness scale , Visual Analog Scale-Pain Intensity ( VAS-PI ) overall and subcomponent scores , and HAM-D(17 ) response and remission rates . The study was conducted from June 2003 to May 2004 . RESULTS Of the 247 patients r and omly assigned to treatment , 234 comprised the intent-to-treat population . Following titration , mean daily desvenlafaxine doses ranged from 179 to 195 mg/day . At endpoint , there were no significant differences in scores between the desvenlafaxine ( N = 120 ) and placebo ( N = 114 ) groups on the HAM-D(17 ) or CGI-I. However , the desvenlafaxine group had significantly greater improvement in MADRS scores ( p = .047 ) and in VAS-PI overall pain ( p = .008 ) , back pain ( p = .006 ) , and arm , leg , or joint pain ( p < .001 ) scores than the placebo group . The most common treatment-emergent adverse events ( at least 10 % and twice the rate of placebo ) were nausea , dry mouth , constipation , anorexia , somnolence , and nervousness . CONCLUSION Desvenlafaxine was generally safe and well tolerated . In this study , it did not show significantly greater efficacy than placebo on the primary or key secondary efficacy endpoints , but it did demonstrate efficacy on an alternate depression scale and pain measure associated with MDD . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00063206 BACKGROUND Approximately 45 % of patients with major depressive disorder ( MDD ) do not remit when treated with biogenic amine antidepressants . Consequently , there is a significant need for antidepressant agents with different mechanisms of action . Early proof of concept ( POC ) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research . Studies have demonstrated that high affinity N-methyl-Daspartate ( NMDA ) receptor blockers ( eg , ketamine ) can produce rapid antidepressant effects in patients who have not responded to currently available agents , but treatment with these agents is accompanied by psychotomimetic effects that make their use problematic . This column describes a POC study involving GLYX-13 , an N-methyl-D-aspartate receptor glycine site functional partial agonist . METHOD In this double-blind , r and omized , placebo-controlled study , a single intravenous ( IV ) dose of GLYX-13 ( 1 , 5 , 10 , or 30 mg/kg ) or placebo was administered to 116 subjects with MDD who had not benefitted from a trial of at least one biogenic amine antidepressant during the current episode . The primary outcome measure was score on the Hamilton Depression Rating Scale-17 ( Ham-D17 ) , which was used to rate overall depressive symptoms at baseline and at 24 hours and days 3 , 7 , 14 , and , in some arms , days 21 and 28 after administration . RESULTS GLYX-13 , 5 or 10 mg/kg IV , reduced depressive symptoms as assessed by the Ham-D17 at days 1 through 7 . Onset of action as assessed using the Bech-6 occurred within 2 hours . GLYX-13 did not elicit psychotomimetic or other significant side effects . CONCLUSION In this early POC study , GLYX-13 reduced depressive symptoms within 2 hours and this effect was maintained for 7 days on average in subjects with MDD who had not responded to another antidepressant agent during the current depressive episode . The findings of this study support the hypothesis that modulation of the NMDA receptor is a valid target for the development of antidepressant drugs and the need for additional studies to further evaluate the effects of GLYX-13 . POC studies such as the one described here play a pivotal role in allowing drug research ers to decide whether to move forward with larger and more expensive studies , and they enable them to focus available re sources on those molecules that appear to have the most therapeutic promise . Based on the POC study described here , a multiple dose study has been completed which showed sustained therapeutic benefit with repeated dosing of GLYX-13 for more than 6 weeks . Phase 3 studies are now being planned Objective : To investigate the use of bright light therapy as an adjunct treatment to  sertraline  in non‐seasonal major depression BACKGROUND This r and omized , open-label , rater-blinded , multicenter study compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine extended release ( ER ) with selective serotonin reuptake inhibitors ( SSRIs ) in primary care patients with major depressive disorder . METHOD Study data were collected from November 29 , 2000 , to March 4 , 2003 . Out patients who met diagnostic criteria for major depressive disorder according to the Mental Health Screener , a computer-administered telephone interview program that screens for the most common mental disorders , and had a total score on the 17-item Hamilton Depression Rating Scale ( HDRS(17 ) ) ≥ 20 were r and omly assigned to receive up to 6 months of open-label venlafaxine ER 75 - 225 mg/d ( n = 688 ) or an SSRI ( n = 697 ) : fluoxetine 20 - 80 mg/d , paroxetine 20 - 50 mg/d , citalopram 20 - 40 mg/d , and sertraline 50 - 200 mg/d . The primary outcome was remission ( HDRS(17 ) score ≤ 7 ) at study end point using the last-observation-carried-forward method to account for early termination . A mixed-effects model for repeated measures ( MMRM ) analysis evaluated secondary outcome measures . RESULTS Fifty-one percent of patients completed the study . Month 6 remission rates did not differ significantly for venlafaxine ER and the SSRIs ( 35.5 % vs 32.0 % , respectively ; P = .195 ) . The MMRM analysis of HDRS(17 ) scores also did not differ significantly ( P = .0538 ) . Significant treatment effects favoring the venlafaxine ER group were observed for remission rates at days 30 , 60 , 90 , and 135 and a survival analysis of time to remission ( P = .006 ) , as well as Clinical Global Impressions-severity of illness scale ( P = .0002 ) ; Hospital Anxiety and Depression Scale-Anxiety subscale ( P = .03 ) ; 6-item Hamilton Depression Rating Scale , Bech version ( P = .009 ) ; and Quick Inventory of Depressive Symptomatology-Self-Report ( P = .0003 ) . CONCLUSIONS Remission rates for patients treated with venlafaxine ER or an SSRI did not differ significantly after 6 months of treatment . Results of most secondary analyses suggested that SNRI treatment had a greater antidepressant effect versus the SSRIs studied OBJECTIVE This study investigated the efficacy , safety , and tolerability of the selegiline transdermal system ( STS ) administered in a dose range of 6 mg/24 hours to 12 mg/24 hours for treating major depressive disorder ( MDD ) . METHOD Patients meeting DSM-IV criteria for MDD ( N = 265 ) were r and omly assigned to blinded treatment with STS or a matching placebo patch for 8 weeks . Patients failing to meet or maintain protocol -defined therapeutic response criteria at predetermined time points had their STS ( or placebo ) dose increased . Assessment s were conducted at weeks 1 , 2 , 3 , 5 , 6 , and 8 . Patients were not required to follow a tyramine-restricted diet . The study ran from September 2001 through August 2002 . RESULTS Selegiline transdermal system treatment result ed in significantly greater improvement ( p < or = .05 ) compared with placebo treatment on the 3 depression rating scales : the 28-item Hamilton Rating Scale for Depression ( HAM-D28 ) ( primary outcome measure ) , the Montgomery-Asberg Depression Rating Scale , and the Inventory for Depressive Symptomatology-Self Rated . The treatment effect measured by the HAM-D28 was modest , primarily due to insomnia side effects . The antidepressant efficacy of STS was substantiated further by the significantly greater improvement in core depression symptoms ( HAM-D Bech-6 subscale ) . The side effects of highest incidence were application site reactions and insomnia . There were no safety concerns based on routine clinical laboratory and electrocardiogram monitoring , and there were no occurrences of hypertensive crisis . CONCLUSION Results of this double-blind , placebo-controlled , dose titration trial provide evidence of short-term efficacy , safety , and tolerability of STS in the dose range of 6 mg/24 hours to 12 mg/24 hours for treatment of MDD . Selegiline transdermal system has an improved margin of safety compared with oral monoamine oxidase inhibitors and represents a useful addition to the existing array of antidepressants OBJECTIVES To compare the sensitivity of the 6-item  Hamilton Rating Scale for Depression  ( HRSD6 ) with the more widely used 17-item  Hamilton Rating Scale for Depression  ( HRSD17 ) in patients suffering from major depressive disorder , with or without melancholia and /or dysthymic disorder . A secondary objective was to compare the sensitivity of the HRSD6 to the Montgomery-Asberg Depression Rating Scale ( MADRS ) . DESIGN Retrospective analysis of 4 clinical trials that tested antidepressant therapies . SETTING Outpatient treatment in a major psychiatric hospital . PARTICIPANTS One hundred and forty-three male and female out patients meeting the criteria of the DSM-III-R or DSM-IV for major depressive disorder . OUTCOME MEASURES HRSD17 , HRSD6 and MADRS . RESULTS The HRSD6 correlated strongly with the HRSD17 , both at baseline and termination of treatment , and for the subgroups of double depression and melancholia . The HRSD6 was also correlated significantly with the MADRS at both measurement times , and for the subgroups . Paired t-tests with the HRSD6 , HRSD17 and MADRS demonstrated equal sensitivity to change over the course of treatment , both in the full sample and in the dysthymic and melancholic subgroups . CONCLUSIONS The HRSD6 appears to be as sensitive to change over treatment as the HRSD17 and the MADRS . A shorter , less time-consuming measure of depression may have utility in clinical practice and research In clinical pharmacology , the evidence proving that a drug has a therapeutic effect in a specific medical condition is based on two major elements : superiority of the drug over placebo in r and omized clinical trials within the medical condition under examination , and a systematic relationship between the dose of the drug and the magnitude of the response it elicits . In their overview of antidepressants versus placebo , Khan and Brown ( 1 ) conclude that “ no clear dose-response relationship has been established to date for most of the new antidepressants ” , while the superiority of the antidepressants over placebo in terms of effect size statistics is approximately 0.30 , a level they find “ less than impressive ” . In their review of double-blind , placebo-controlled trials of antidepressants conducted from 1981 to 2008 , Khan et al ( 2 ) observed that the Hamilton Depression Scale ( HAM-D ) had been used as an outcome scale in most of the trials . However , the HAM-D was actually used in two different versions , the 21-item version ( HAM-D-21 ) and the 17-item version ( HAM-D-17 ) . The HAM-D-21 was used in one third of the trials and the HAM-D-17 in two thirds . Unfortunately , authors who use the HAM-D-21 rarely provide information about the results on the HAM-D-17 . Khan and Brown ( 1 ) highlight now that the antidepressant-placebo difference seems to be higher in HAM-D-21 trials compared to the trials in which the HAM-D-17 has been used as outcome measure . This is a tautological finding in so far as the st and ard deviation of this difference is not available , which is the case for most of the trials review ed by Khan et al ( 2 ) . Among the trials collected by Khan et al ( 2 ) it is possible , however , to identify ten publications in which the six-item HAM-D ( HAM-D-6 ) is compared to both HAM-D-17 and HAM-D-21 , or to HAM-D-28 . The HAM-D-6 covers the core symptoms of depression : depressed mood , work and interests , guilt feelings , psychomotor retardation , psychic anxiety , and general somatic ( fatigability ) . These six items have clinical and psychometric validity ( 3 ) . In two of these ten trials , a dose-response relationship was investigated . Fabre et al ( 4 ) showed that sertraline was significantly superior to placebo at all three doses ( 50 , 100 , 200 mg daily ) when using HAM-D-6 , but only at 50 mg daily when using HAM-D-17 . Liebowitz et al ( 5 ) showed that desvenlafaxine was superior to placebo at both 50 and 100 mg daily when using HAM-D-6 , but only at 50 mg daily when using HAM-D-17 . An analysis of all placebo-controlled trials of desvenlafaxine showed that at doses of 200 or 400 mg daily the effect size was negative during the first week of treatment ( superiority of placebo ) when using HAM-D-17 but not when using the HAM-D-6 , implying that the HAM-D-17 includes symptoms which might be side effects of the drug ( 6 ) . In placebo-controlled trials of fluoxetine , over a dose range from 20 to 60 mg daily , the effect size using HAM-D-17 was approximately 0.30 , but when using HAM-D-6 it was approximately 0.40 ( 3 ) . For escitalopram , a dose of 10 mg daily obtained an effect size of 0.38 mg using HAM-D-6 and a dose of 20 mg daily gave an effect size of 0.61 ( 3 ) . Over the past decade , the goal when evaluating the effect of an antidepressant has been the event of remission rather than response ( 7 ) . Remission in major depression is defined as a minimal level of the core symptoms of depression ( 7 ) . The syndrome reflected by the HAM-D-6 is a unidimensional measure for specific drug targets , and a cut-off score below 5 indicates that the individual symptoms of the scale are only present to a very doubtful degree ( remission ) . Khan and Brown ( 1 ) refer to the Sequenced Treatment Alternatives to Relieve Depression ( STAR*D ) as an example of a poor response to citalopram treatment . Indeed , when using the conventional definition of remission ( HAM-D-17 < 8) , only approximately 36 % of the patients  achieved remission . However , when using a HAM-D-6 score of < 5 as the definition of remission , approximately 45 % of the patients in that study achieved remission ( p<0.001 ) ( 8) . From a statistical point of view , failed trials are merely a consequence of insufficient power , as the inability to reject the null hypothesis is inherently associated with low statistical power . This has recently been illustrated in a re- analysis of a failed study which had used the HAM-D-17 to evaluate the effect of erythropoietin as augmentation in patients with treatment-resistant depression ( 9 ) . By focusing on the HAM-D-6 , fewer patients are needed to reject the null hypothesis . Psychometrically , Khan and Brown ( 1 ) correctly focus on the use of the HAM-D-17 as the major factor for the “ less than impressive ” effect size of 0.30 and the lack of a dose-response relationship . However , their solution to go for a larger HAM-D version ( HAM-D-21 ) is not justified . The solution is to go for the brief , clinical ly and psychometrically valid subscale ( HAM-D-6 ) . The use of the HAM-D-6 as outcome measure in placebo-controlled clinical trials of antidepressants increases the effect size to 0.40 , which is indicative of clinical significance . Using the HAM-D-6 as outcome measure , a dose-response relationship has been established for newer antidepressants such as escitalopram and desvenlafaxine . Moreover , fewer patients are then needed to identify antidepressant effect in controlled trials , which has important ethical implication s ( fewer patients need to receive placebo ) . In my opinion , we need to aim at establishing “ dose-remission ” rather than dose-response relationship in future trials of antidepressants . The HAM-D-6 contains the core symptoms of depression by which to define the event of remission Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression , based on data on all r and omized clinical trials using the  Hamilton Depression Scale ( HAMD  ) su bmi tted to FDA , have shown an effect size of approximately 0.30 in favour of antidepressants in the acute therapy of major depression . The clinical significance of an effect size at this level was found to be so poor that these meta-analyses have subscribed to the myth of an exclusively placebo-like effect of second-generation antidepressants . A re-allocation of HAMD items focusing on those items measuring severity of clinical depression , the HAMD6 , has identified effect sizes of > or=0.40 for second-generation antidepressants in placebo-controlled trials for which even a dose-response relationship can be demonstrated . In the relapse-prevention phase during continuation therapy of patients with major depression , the advantage of second-generation antidepressants over placebo was as significant as in the acute therapy phase . To explore a myth is not to deny the facts but rather to re-allocate them INTRODUCTION This retrospective analysis compared sensitivity to change on the 17-item and 6-item Hamilton Rating Scales For Depression ( HAM-D ( 17 ) and HAM-D ( 6 ) , respectively ) in relation to antidepressant dose and baseline depression severity . METHODS Data were derived from 6 r and omized , double-blind , placebo-controlled , 8-week trials of  fixed-dose desvenlafaxine  ( 50 , 100 , 200 or 400 mg/d ) for major depressive disorder .  HAM-D ( 17 ) and HAM-D ( 6 ) effect sizes were assessed . RESULTS HAM-D ( 17 ) effect sizes were negative ( favoured placebo ) for higher desvenlafaxine doses ( 200 - 400 mg/d ) at week 1 , but were positive for all doses after week 2 , with no clear dose-response pattern . However , HAM-D ( 6 ) effect sizes were positive for all doses at all weeks . Effect sizes were consistently greater for HAM-D ( 6 ) vs. HAM-D ( 17 ) , regardless of time spent under therapy . Effect sizes were greater for HAM-D ( 6 ) vs. HAM-D ( 17 ) for all desvenlafaxine doses among patients with baseline HAM-D ( 17 ) < 25 , but not among patients with baseline HAM-D ( 17 ) ≥ 25 . DISCUSSION The HAM-D ( 6 ) demonstrated greater sensitivity to change and robustness than the HAM-D ( 17 ) , supporting the greater homogeneity of the HAM-D ( 6 )
target: Conclusions : According to the published literature , the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS .
background: Background : In a study aim ed at identifying the items carrying information regarding the global severity of depression , the 6-item Hamilton Depression Rating Scale ( HAM-D6 ) was derived from the original 17-item version of the scale ( HAM-D17 ) .
  Since then , the HAM-D6 has been used in a wide range of clinical studies .
  We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale ( MADRS ) .