HAM-D17 and HAM-D6 sensitivity to change in relation to desvenlafaxine dose and baseline depression severity in major depressive disorder. Paroxetine in the treatment of depressed patients with haematological malignancy: an open-label study. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group. Sexual Functioning in Patients With Recurrent Major Depressive Disorder Enrolled in the PREVENT Study Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. Quetiapine in the treatment of anxiety in patients with bipolar I or II depression: a secondary analysis from a randomized, double-blind, placebo-controlled study. Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. Once-Daily Venlafaxine Extended Release (XR) and Venlafaxine Immediate Release (IR) in Outpatients with Major Depression The 16-Item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression Influence of Cognitive Behavioral Therapy on Mood and Quality of Life After Stent Implantation in Young and Middle-Aged Patients With Coronary Heart Disease. A randomized controlled trial comparing moclobemide and moclobemide plus interpersonal psychotherapy in the treatment of dysthymic disorder. Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression. Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression. Symptomatic and Functional Improvement in Employed Depressed Patients: A Double-Blind Clinical Trial of Desvenlafaxine Versus Placebo A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. Hamilton depression rating scale and montgomery–asberg depression rating scale in depressed and bipolar I patients: psychometric properties in a Brazilian sample The responsiveness of the different versions of the Hamilton Depression Scale. Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. St. John's wort extract LI160 for the treatment of depression with atypical features - a double-blind, randomized, and placebo-controlled trial. Lithium augmentation of venlafaxine: an open-label trial. Mirtazapine Versus Venlafaxine in Hospitalized Severely Depressed Patients With Melancholic Features The efficacy and tolerability of venlafaxine and paroxetine in outpatients with depressive disorder or dysthymia A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. Placebo-controlled inpatient comparison of venlafaxine and fluoxetine for the treatment of major depression with melancholic features Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study. Escitalopram in major depressive disorder: a multicenter, randomized, double‐blind, fixed‐dose, parallel trial in a Chinese population Patient outcomes with education, drug therapy, and support: a study of venlafaxine ER-treated outpatients with major depressive disorder. Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies. A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression Paroxetine versus placebo: a double-blind comparison in depressed patients. A double-blind, placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression.
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 ) OBJECTIVE The efficacy and tolerability of paroxetine in the treatment of depressive disorders is well known , however , its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied . Therefore this study was aim ed at evaluating the efficacy and tolerability of paroxetine in the treatment of depressed patients with haematological malignancy ( HM ) . METHOD Fifty-two patients with major depressive disorder ( MDD ) based on DSM-IV criteria along with comorbid HM were allotted to an 8 week trial with a flexible-dose regime of paroxetine in combination with their chemotherapy or supportive pharmacotherapy . The treatment response was assessed at baseline , week 2 , week 4 and week 8 with the  17-item Hamilton rating scale for depression ( HAM-D17 ) , the Montgomery Asberg depression rating scale ( MADRS ) and the clinical global impression-severity ( CGI-S ) . Side effects were collected with reported adverse events and laboratory tests throughout the study period . RESULTS 44.2 % of 52 patients completed the 8 week trial . Scores on the HAM-D17 , MADRS and CGI-s ( last observation carried forward , LOCF ) at baseline were significantly reduced with a mean reduction of 30.5 % , 32.8 % and 39.1 % , respectively , after 8 weeks treatment with paroxetine . CONCLUSION In this preliminary study , paroxetine was found to be effective and moderately tolerated in the treatment of depressed patients with HM , and the present study calls for a controlled study in this field to extend and form a framework on the psychopharmacological data in this field BACKGROUND Despite the high prevalence of depression in elderly patients , few well- design ed , placebo-controlled studies of antidepressants have been conducted in this population . This masked , placebo-controlled trial assessed the efficacy and safety of venlafaxine and fluoxetine in depressed patients older than 65 years . METHOD Three hundred patients were r and omly assigned to treatment with venlafaxine immediate release ( [ IR ] ; N = 104 ) , fluoxetine ( N = 100 ) , or placebo ( N = 96 ) in an eight-week trial . Venlafaxine doses were titrated from 37.5 to 225 mg per day and fluoxetine doses were titrated from 20 to 60 mg per day , as necessary , over 29 days . Efficacy variables included the 21-item Hamilton Depression Rating Scale ( HAM-D21 ) total score , HAM-D21 depressed mood item score , scores on the Montgomery Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression-Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales , and rates of response ( based on change from baseline HAM-D or MADRS score or CGI-I score ) and remission ( HAM-D17 < or = 7 ) . For the purpose s of this report , efficacy analyses are focused on the HAM-D21 total score . Safety assessment s included monitoring of adverse events ( AEs ) , physical examinations , vital signs assessment s , laboratory determinations , and electrocardiograms . RESULTS In all three of the treatment groups , there was a significant reduction at week 8 compared with the baseline HAM-D21 total score . However , there were no significant differences among the three treatment groups on the change in HAM-D21 , MADRS , or CGI scores from baseline to week 8 . There was no statistically significant difference in the proportion of remitters at the last on-therapy visit . The incidence of individual AEs was higher in the venlafaxine group ( 27 % ) compared with patients taking fluoxetine ( 19 % ) or placebo ( 9 % ) . CONCLUSION In this study , there was no significant difference in efficacy among placebo , venlafaxine , and fluoxetine for the treatment of depression BACKGROUND This was a r and omized , double-blind , placebo-controlled evaluation of the efficacy and safety of once-daily venlafaxine extended release ( XR ) in out- patients with DSM-IV major depression . METHOD Patients were r and omly assigned to venlafaxine XR ( 75 - 225 mg ) once daily or placebo for up to 8 weeks . The primary efficacy variables were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) total score and HAM-D depressed mood item , the Montgomery-Asberg Depression Rating Scale ( MADRS ) total scores , and the Clinical Global Impressions ( CGI ) Severity scale . Data were analyzed on a modified intent-to-treat basis using the last-observation-carried-forward method . RESULTS Venlafaxine XR ( N = 91 ) was significantly more effective than placebo ( N = 100 ) beginning at Week 2 on the CGI Severity scale , at Week 3 on the HAM-D depressed mood item , and at Week 4 on the HAM-D and MADRS ; this superiority was maintained through Week 8 . The most common treatment-emergent adverse events associated with venlafaxine XR were nausea , insomnia , and somnolence . The incidence of nausea was highest during the first week , decreased by 50 % during the second week , and was comparable to that of placebo from Week 3 onward . CONCLUSION These results demonstrate that venlafaxine XR is an effective and well-tolerated treatment of major depression Abstract The incidence of treatment-emergent sexual dysfunction in the acute and continuation phases of the prevention of recurrent episodes of depression with venlafaxine ER for two years ( PREVENT ) study was assessed . Adult out patients with recurrent major depressive disorder were r and omly assigned to receive venlafaxine extended release ( ER ; 75–300 mg/day ) or fluoxetine ( 20–60 mg/day ) . Sexual dysfunction was assessed using items from the 17-item Hamilton Rating Scale for Depression ( HAM-D17 ) and the Inventory of Depressive Symptomatology – Self-Report ( IDS-SR ) . The baseline rates of sexual dysfunction based on the HAM-D17 and IDS-SR items were 57.9 % and 48.8 % , respectively . The rates of new-onset sexual dysfunction for the venlafaxine ER – treated ( 44.8 % , HAM-D17 ; 38.4 % , IDS-SR ) and fluoxetine-treated patients ( 52.9 % , HAM-D17 ; 50.0 % , IDS-SR ) were similar ; approximately 80 % of the cases resolved during treatment . Treatment response was associated with lower rates of new-onset sexual dysfunction compared with nonresponse . The patients who remitted were the least likely to experience sexual dysfunction during antidepressant treatment BACKGROUND This 8-week , double-blind , r and omized trial compared the efficacy and tolerability of venlafaxine and sertraline in patients with major depression . METHOD Out patients ( N = 147 ) with DSM-IV major depressive disorder and a baseline 21-item Hamilton Rating Scale for Depression ( HAM-D ) score of at least 18 were r and omly assigned to venlafaxine , 37.5 mg b.i.d . , or sertraline , 50 mg once daily . From day 15 , the doses could be increased to venlafaxine , 75 mg b.i.d . , or sertraline , 50 mg b.i.d . Efficacy was assessed with the 21-item HAM-D , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale ( CGI ) using a modified intent-to-treat analysis . RESULTS No significant differences were noted between treatments for mean HAM-D , MADRS , or CGI scores . At week 8 , the HAM-D response rate was 83 % with venlafaxine ( N = 75 ) and 68 % with sertraline ( N = 72 ) ( p = .05 ) . A HAM-D score less than 10 was recorded in 68 % of venlafaxine-treated and 45 % of sertraline-treated patients at week 8 ( p = .008 ) . Among patients who increased their dose , the remission rate ( HAM-D score < 10 ) was 67 % with venlafaxine and 36 % with sertraline at week 8 ( p < .05 ) . The overall discontinuation rate was 21 % with venlafaxine and 17 % with sertraline . The most common adverse events with venlafaxine were nausea , headache , and sweating and with sertraline were nausea , headache , and diarrhea . CONCLUSION Among patients who increased their dose , approximately twice as many experienced a remission with venlafaxine , which is a more clinical ly relevant endpoint than response and represents the proportion of patients who have recovered or are well OBJECTIVE Quetiapine monotherapy shows efficacy in bipolar depression . The analyses in this multicenter , double-blind , r and omized , fixed-dose , placebo-controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms in bipolar depression . METHOD Of 542 out patients r and omly assigned to treatment , 539 with bipolar I ( N = 358 ) or bipolar II ( N = 181 ) disorder experiencing a major depressive episode ( DSM-IV ) received 8 weeks of quetiapine monotherapy ( 600 or 300 mg/day ) or placebo between September 2002 and October 2003 . Anxiety assessment s included the Hamilton Rating Scale for Anxiety ( HAM-A ) and relevant items from the Montgomery-Asberg Depression Rating Scale ( MADRS ) and Hamilton Rating Scale for Depression ( HAM-D ) . Analyses evaluated the pooled dose groups versus placebo . RESULTS At week 8 , quetiapine 600 and 300 mg/day each demonstrated significant improvements in HAM-A total score versus placebo ( -10.8 and -9.9 vs. -6.7 , p < .001 ) . Quetiapine ( pooled doses ) significantly improved HAM-A total score from week 1 . In bipolar I depression , quetiapine showed significant improvement in HAM-A total score versus placebo ( -10.4 vs. -5.1 , p < .001 ) . In bipolar I depression , quetiapine also showed significant improvements versus placebo on the HAM-A anxious mood and tension items , HAM-A psychic and somatic subscales , MADRS inner tension item , and HAM-D psychic anxiety item ( all p < .001 ) , but not the HAM-D somatic anxiety item . In bipolar II depression , quetiapine reduced the HAM-A total score more than placebo , but the difference was not statistically significant ( -9.8 vs. -9.0 , p = .473 ) . In bipolar II depression , quetiapine showed significant improvement versus placebo on the HAM-A anxious mood , MADRS inner tension , and HAM-D psychic anxiety items ( all p < .01 ) . CONCLUSION Quetiapine monotherapy shows efficacy in treating anxiety symptoms in bipolar I depression ; however , the anxiolytic effects in bipolar II disorder require further investigation OBJECTIVE The efficacy and tolerability of vilazodone , a combined selective serotonin reuptake inhibitor and partial 5-hydroxytryptamine-1A ( 5-HT(1A ) ) receptor agonist , were evaluated in adult patients with major depressive disorder ( MDD ) . METHOD This was a r and omized , double-blind , placebo-controlled trial conducted from February 2006 to May 2007 . Patients aged 18 through 65 years with MDD ( DSM-IV criteria ) and a baseline 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) score of > or= 22 were r and omly assigned to vilazodone or placebo for 8 weeks .  Vilazodone was titrated from 10 mg to 40 mg once a day over 2 weeks .  Efficacy was assessed by mean change from baseline to week 8 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , HAM-D-17 , and Hamilton Rating Scale for Anxiety . Response rates were determined at week 8 for the MADRS , HAM-D-17 , and Clinical Global Impressions-Severity of Illness ( CGI-S ) and -Improvement ( CGI-I ) scales . Data were analyzed using a modified last-observation-carried-forward method in the intention-to-treat ( ITT ) sample . The Arizona Sexual Experience Scale ( ASEX ) was also measured at baseline and week 8 . RESULTS Of 410 r and omly assigned patients , 198 receiving vilazodone and 199 receiving placebo were included in the ITT population . The mean changes in MADRS and HAM-D-17 total scores from baseline to week 8 were significantly ( p = .001 and p = .022 , respectively ) greater with vilazodone than with placebo . Significant ( p < .05 ) improvements in MADRS and HAM-D-17 scores were noted at week 1 , the earliest time point measured . Response rates were significantly higher with vilazodone than with placebo on the MADRS ( p = .007 ) , HAM-D-17 ( p = .011 ) , and CGI-I ( p = .001 ) . Treatment-emergent adverse events with vilazodone included diarrhea , nausea , and somnolence ; most adverse events were of mild or moderate intensity . There were no clinical ly significant differences for either gender in ASEX scores at end of treatment . CONCLUSIONS Vilazodone is effective for the treatment of MDD in adults , with symptom relief starting at 1 week , and is well tolerated at a dose of 40 mg/day . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00285376 This was a r and omized , double-blind , placebo-controlled comparison of the efficacy and safety of once-daily venlafaxine extended release ( XR ) and venlafaxine immediate release ( IR ) . Out patients with DSM-III-R major depression were r and omly assigned to venlafaxine XR , 75 mg once daily , venlafaxine IR , 37.5 mg twice daily , or placebo for a maximum of 12 weeks . If the response was inadequate after 2 weeks of treatment , the dosage of venlafaxine XR or IR could be increased to 150 mg daily . The primary efficacy variables were the 21-item Hamilton Depression ( HAM-D ) Rating Scale total score and depressed mood item , the Montgomery – Asberg Rating Scale ( MADRS ) total scores , and the Clinical Global Impressions ( CGI ) severity scale .  Two hundred seventy-eight patients were evaluated for efficacy . Venlafaxine XR was significantly superior ( p < 0.05 ) to placebo beginning at week 2 for the HAM-D , week 3 for the MADRS , and week 4 for the CGI severity . Similarly , venlafaxine IR was significantly superior ( p < 0.05 ) to placebo beginning at week 2 on the HAM-D total and depressed mood item , week 3 on the MADRS total , and week 6 on the CGI severity scales .  Venlafaxine XR exhibited superiority ( p < 0.05 ) over venlafaxine IR at week 12 for all efficacy variables . The most common treatment-emergent adverse event with venlafaxine XR was nausea . The incidence of nausea was highest during the first 2 weeks with a low likelihood of developing nausea thereafter . The results of this study indicate that venlafaxine XR is safe , effective , and well tolerated for the treatment of major depression at once-daily doses ranging from 75 to 150 mg The 16-item Quick Inventory of Depressive Symptomatology ( QIDS ) , a new measure of depressive symptom severity derived from the 30-item Inventory of Depressive Symptomatology ( IDS ) , is available in both self-report ( QIDS-SR(16 ) ) and clinician-rated ( QIDS-C(16 ) ) formats . This report evaluates and compares the psychometric properties of the QIDS-SR(16 ) in relation to the IDS-SR(30 ) and the 24-item Hamilton Rating Scale for Depression ( HAM-D(24 ) ) in 596 adult out patients treated for chronic nonpsychotic , major depressive disorder .  Internal consistency was high for the QIDS-SR(16 ) ( Cronbach 's alpha = .86 ) , the IDS-SR(30 ) ( Cronbach 's alpha = .92 ) , and the HAM-D(24 ) ( Cronbach 's alpha = .88 ) .  QIDS-SR(16 ) total scores were highly correlated with IDS-SR(30 ) ( .96 ) and HAM-D(24 ) ( .86 ) total scores . Item-total correlations revealed that several similar items were highly correlated with both QIDS-SR(16 ) and  IDS-SR(30 ) total scores . Roughly 1.3 times the QIDS-SR(16 )  total score is predictive of the HAM-D(17 ) ( 17-item version of the HAM-D ) total score . The QIDS-SR(16 ) was as sensitive to symptom change as the IDS-SR(30 ) and HAM-D(24 ) , indicating high concurrent validity for all three scales . The QIDS-SR(16 ) has highly acceptable psychometric properties , which supports the usefulness of this brief rating of depressive symptom severity in both clinical and research setting Cognitive behavioral therapy ( CBT ) , established only a few decades ago , is widely used by clinical psychologists . This study aim ed to investigate the effects of CBT on mental status and quality of life ( QOL ) after percutaneous coronary intervention ( PCI ) in young and middle-aged patients with coronary heart disease ( CHD ) . Seventy-five anxiety/depression patients ( mean age , 52.2 ± 6.2 years , including 8 individuals < 45 years old ) with CHD treated with PCI were r and omly divided into a CBT group ( n = 38 ) and control group ( n = 37 ) . The CBT group received 8 weeks of CBT in addition to the routine postoperative treatment that was also administered to control patients . The 17-item Hamilton Depression Rating Scale ( HAM-D17 ) , Hamilton anxiety scale ( HAM-A ) , and Coronary Revascularization Outcome Question naire ( CROQ-PTCA-POST , Chinese version ) were administered before , 3 days , and 8 weeks after intervention . HAM-D17 and HAM-A scores were decreased after treatment , but were more substantially reduced in patients that underwent CBT than those in the control group ( 11.7 ± 4.5 versus 15.1 ± 3.9 , P = 0.001 and 10.6 ± 3.4 versus 16.5 ± 4.6 , P = 0.003 , respectively ) . QOL was improved in both groups , but overall satisfaction was higher in the CBT group compared with control patients ( 89.3 ± 5.2 versus 77.8 ± 9.5 , P < 0.05 ) . CBT can relieve depression and anxiety after PCI in young and middle-aged patients with CHD . CBT can improve patient QOL The authors compared the outcomes of 35 out patients with dysthymic disorder r and omized to receive either treatment with moclobemide and interpersonal therapy ( IPT ) or moclobemide and routine clinical management .  Diagnosis was based on the ICD-10 symptom checklist . Patients were evaluated by trained raters using the 17-item Hamilton Rating Scale for Depression ( Ham-D ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , Global Assessment of Functioning , and Quality of Life and Satisfaction Question naire at baseline , 12 , 24 , and 48 weeks . Patients in both treatment groups showed statistically significant improvement in all measures across time . There was a nonsignificant trend toward lower scores on Ham-D and MADRS for patients in the moclobemide plus IPT group . Longer , better-powered trials should be carried out to study the efficacy of  IPT plus antidepressant medication  in the treatment of dysthymic disorder Depressive illness among the elderly is an important public health concern . However , treatment of the elderly may be complicated by age-related changes in physiology , general medical status , and susceptibility to side effects . There is therefore a need for improved treatment modalities for depressed elderly patients .  Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake . It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants . The authors present the combined data from two similarly design ed comparisons of paroxetine and doxepin in out patients over 60 years of age with major depression . The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression ( HAM-D ) total score , the Montgomery and Asberg Depression Rating Scale ( MADRS ) , and the Hopkins Symptom Checklist ( SCL ) depression factor score .  Paroxetine was significantly superior to doxepin on the Clinical Global Impressions ( CGI ) scale for severity of illness , the HAM-D retardation factor , and the HAM-D depressed mood item .  Doxepin produced significantly more anticholinergic effects , sedation , and confusion . Paroxetine was associated with more reports of nausea and headache . These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly BACKGROUND Citalopram , the most selective serotonin reuptake inhibitor ( SSRI ) , is a bicyclic phthalane derivative with a chemical structure that is unrelated to that of other SSRIs and available antidepressants . The drug is approved for use in 69 countries . This 6-week , fixed-dose , placebo-controlled , parallel-arm , multicenter trial was performed to confirm its efficacy and safety in treatment of out patients with major depression in the United States . METHOD Six hundred and fifty adult out patients with moderate-to-severe major depression ( DSM-III-R ) were r and omly assigned to receive citalopram at doses of 10 mg ( N = 131 ) , 20 mg ( N = 130 ) , 40 mg ( N = 131 ) , or 60 mg ( N = 129 ) or placebo ( N = 129 ) once daily . Outcome assessment s were the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions scale . RESULTS Between-group comparisons of the change from baseline to endpoint revealed significantly greater improvement in the citalopram patients relative to the placebo patients on all 3 efficacy measures . Patients r and omly assigned to 40 mg/day and 60 mg/day of citalopram showed significantly greater improvement than placebo on all efficacy measures , as well as on the HAM-D symptom clusters measuring depressed mood , melancholia , cognitive disturbance , and psychomotor retardation . Patients who received 10 mg/day and 20 mg/day of citalopram also showed consistent improvement relative to placebo on all efficacy ratings , with statistical significance demonstrated in the MADRS response rate , the HAM-D depressed mood item , and the HAM-D melancholia subscale . Citalopram was well tolerated , with only 15 % of patients discontinuing for adverse events . The side effects most commonly associated with citalopram treatment were nausea , dry mouth , somnolence , insomnia , and increased sweating . CONCLUSION Citalopram was significantly more effective than placebo in the treatment of moderate-to-severe major depression , especially symptoms of depressed mood and melancholia , with particularly robust effects shown at doses of 40 and 60 mg/day . Citalopram was well tolerated in spite of forced upward titration to fixed-dose levels , with a low incidence of anxiety , agitation , and nervousness Objective : This is the first study to assess the efficacy of desvenlafaxine ( administered as desvenlafaxine succinate ) for improving depressive symptoms and functioning exclusively in employed patients with major depressive disorder ( MDD ) . Methods : Gainfully employed ( ≥20 h/wk ) male and female out patients with MDD were r and omly assigned ( 2:1 ratio ) to 12 weeks of double-blind treatment with desvenlafaxine 50 mg/d or placebo . Analysis of covariance was used to compare differences in week 12 adjusted mean changes from baseline on the 17-item Hamilton Depression Rating Scale ( HAM-D17 ) ( primary outcome ) and Sheehan Disability Scale ( SDS ) ( key secondary outcome ) in the intent-to-treat ( ITT ) population . A predefined , modified ITT population ( ie , those in the ITT population with baseline HAM-D17 ≥20 ) was also analyzed . Tolerability was assessed by recording adverse events and change on the Arizona Sexual Experience Scale . Results : Baseline HAM-D17  scores for desvenlafaxine ( n = 285 ) and placebo ( n = 142 ) were 22.0 and 21.8 , whereas baseline SDS scores were 19.8 and 20.4 . Adjusted mean differences between desvenlafaxine and placebo were 2.1 ( 95 % confidence interval [ CI ] , 0.78 - 3.46 ; P = 0.002 ) on the HAM-D17 and 1.3 ( 95 % CI , −0.09 to 2.76 ; P = 0.067 ) on the SDS . For the modified ITT sample , desvenlafaxine ( n = 208 ) and  placebo ( n = 102 ) , baseline HAM-D17 scores were 23.8 and 23.9 ; the SDS baseline scores were 20.1 and 20.8 . Mean differences were 2.6 ( 95 % CI , 0.93 - 4.22 ; P = 0.002 ) on the HAM-D17 and 2.1 ( 95 % CI , 0.36 - 3.76 ; P = 0.017 ) on the SDS . Adverse events and Arizona Sexual Experience Scale scores were comparable between groups . Conclusions : Desvenlafaxine 50 mg/d was efficacious for treating MDD in gainfully employed adults . Between-group differences on the SDS narrowly missed statistical significance in the ITT population alone , but the totality of data suggests functional improvements with active treatment BACKGROUND More treatment options for bipolar depression are needed . Currently available antidepressants may increase the risk of mania and rapid cycling , and mood stabilizers appear to be less effective in treating depression than mania . Preliminary data suggest that lamotrigine , an established antiepileptic drug , may be effective for both the depression and mania associated with bipolar disorder . This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression . METHODS Out patients with bipolar I disorder experiencing a major depressive episode ( DSM-IV , N = 195 ) received lamotrigine ( 50  or  200 mg/day ) or placebo as monotherapy for 7 weeks . Psychiatric evaluations , including the Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , Mania Rating Scale , and the Clinical Global Impressions scale for Severity ( CGI-S ) and Improvement ( CGI-I ) were completed at each weekly visit . RESULTS Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D , HAM-D Item 1 , MADRS , CGI-S , and CGI-I compared with placebo . Improvements were seen as early as week 3 . Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures . The proportions of patients exhibiting a response on CGI-I were 51 % , 41 % , and 26 % for lamotrigine 200 mg/day , lamotrigine 50 mg/day , and placebo groups , respectively . Adverse events and other safety results were similar across treatment groups , except for a higher rate of headache in the lamotrigine groups . CONCLUSION Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression Background The Hamilton Depression Rating Scale ( HAM-D ) and the Montgomery – Asberg Depression Scale ( MADRS ) are used worldwide and considered st and ard scales for evaluating depressive symptoms . This paper aims to investigate the psychometric proprieties ( reliability and validity ) of these scales in a Brazilian sample , and to compare responses in bipolar and unipolar patients . Methods The sample comprised 91 patients with either bipolar I or major depressive disorder from a psychiatric institute at São Paulo , Brazil . Participants were recruited and treated by clinicians through the Structured Interview for DSM-IV criteria  , and had previously been interviewed by a trained , blind tester . Results Both scales indicated good reliability properties ; however , the MADRS reliability statistics were higher than those of the HAM-D for detecting initial symptoms of unipolar depression . Correlation between the tests was moderate . Despite demonstrating adequate validity , neither test achieved the levels of sensitivity and specificity required for identification of a cutoff score to differentiate bipolar I and unipolar patients . Conclusions Both scales demonstrate adequate reliability and validity for assessing depressive symptoms in the Brazilian sample , and are good options to complement psychiatric diagnosis , but are not appropriate for distinguishing between the two affective disorder types 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 BACKGROUND This was an 8-week , multicenter , r and omized , double-blind , parallel-group study of the efficacy and tolerability of venlafaxine and fluoxetine . METHOD Out patients with DSM-III-R major depression , a minimum score of 20 on the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , and depressive symptoms for at least 1 month were eligible . Patients were r and omly assigned to treatment with venlafaxine , 37.5 mg twice daily , or fluoxetine , 20 mg once daily . The dose could be increased to venlafaxine , 75 mg twice daily , or fluoxetine , 20 mg twice daily , after 3 weeks for a poor response . The primary efficacy variables were the final on-therapy scores on the HAM-D , Montgomery-Asberg Depression Rating Scale ( MADRS ) , and Clinical Global Impressions Severity of Illness ( CGI-S ) and Improvement ( CGI-I ) scales . RESULTS Three hundred eighty-two patients were r and omly assigned to therapy and included in the intent-to-treat analysis . Both venlafaxine and fluoxetine produced significant reductions from baseline to day 56 in mean HAM-D , MADRS , and CGI-S scores , but no significant differences were noted between groups . Among patients who increased their dose at 3 weeks , significantly ( p < .05 ) more patients taking venlafaxine than taking fluoxetine had a CGI-I score of 1 ( very much improved ) at the final evaluation . The most frequent adverse events were nausea , headache , and dizziness with venlafaxine and nausea , headache , and insomnia with fluoxetine . CONCLUSION These results support the efficacy and tolerability of venlafaxine in comparison with fluoxetine for treating out patients with major depression Preliminary data suggest that hypericum extract LI160 is effective in  atypical depression .  Reported is the outcome of an 8-week double-blind , placebo-controlled , r and omized trial of 600 mg LI160 vs. placebo in patients with vegetative features of atypical depression , i.e. hyperphagia or hypersomnia . One-hundred ( 100 ) patients with mild and 100 patients with moderate severity of a major depression according to ICD-10 were r and omized . Patients needed to meet a score of 2 in at least one of the items 22 - 26 of the Hamilton-Depression-Rating-Scale ( HAM-D ) 28-item version and episode duration of at least 3 months . The primary outcome variable was the relative change of the HAM-D(17 ) from Baseline . Secondary outcome variables were the depression sub-score of the Patient Health Question naire ( PHQ-9 ) , the Clinical Global Impression ( CGI ) , a patient 's satisfaction scale , the Hamilton-Anxiety-Scale ( HAM-A ) and the sum score of atypical vegetative symptoms of the HAM-D(28 ) . The percentage reduction of the HAM-D(17 ) for LI160 compared to placebo approached statistical significance ( p=0.051 ) in the Full Analysis Set (FAS)- population . Using the conventional criterion of the absolute reduction of the HAM-D(17 ) significance was achieved ( p<0.05 ) . No significant benefit could be observed for the sum score of the atypical vegetative items of the HAM-D(28 ; ) however , the sum score of the hypersomnia items ( items 22 - 24 ) showed a significant superiority for LI160 . The HAM-A , PHQ-9 , and CGI-I scales demonstrated superiority of LI160 ( p<0.01 ) . Confining the analysis to moderately depressed patients , a highly significant benefit for the primary outcome variable was revealed . The study supports the beneficial effect of LI160 in depression with atypical features and the validity of the definition of atypical depression on the basis of reversed vegetative signs . Further , it identifies the PHQ-9 as a useful outcome variable in this population The authors conducted an open-label study of the efficacy and tolerability of venlafaxine and of lithium augmentation in out patients with depression who were not responding to venlafaxine . Out patients aged 18 to 70 years were eligible if they had a minimum baseline score of 16 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) .  Patients were started on venlafaxine 37.5 mg twice daily for 1 week . For weeks 2 through 4 , the dose of venlafaxine was increased to 75 mg twice daily , and for weeks 5 through 7 , the dose was further increased to 75 mg three times daily . At the end of the 7-week treatment period , patients with a < 50 % decrease in their HAM-D scores from baseline were given lithium carbonate 600 mg once daily . The dose of lithium carbonate was adjusted to maintain plasma levels in the range of 0.6 to 1.0 mmol/mL. Efficacy was assessed with the 17-item HAM-D , Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impressions Scale . Data were analyzed on an intent-to-treat basis . At the end of the 7-week treatment period , 35 % of patients showed a > or = 50 % decrease in their HAM-D scores from baseline . Lithium augmentation was initiated in 23 patients . The results showed that the addition of lithium was well-tolerated and led to a further decrease in the HAM-D scores , with eight patients responding and two of them presenting a remission . The addition of lithium to venlafaxine was found to be a well-tolerated strategy in treatment-resistant patients The aim of this multicenter , r and omized , double-blind , 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features . Patients with a baseline score of ≥ 25 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to receive treatment with either mirtazapine ( N = 78 , 15–60 mg/day ) or venlafaxine ( N = 79 , 75–375 mg/day , twice a day ) in a rapid up-titration schedule . Efficacy was assessed with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , HAM-D-17 , and Clinical Global Impression scale , and quality of life was assessed with the Quality of Life , Enjoyment , and Satisfaction Question naire and Quality of Life in Depression Scale . Tolerability was assessed with the Utvalg for Kliniske Undersogelser ( UKU ) side effect scale and by reporting adverse events . Both drugs were effective in reducing overall symptoms of depression , showing substantial reductions in group mean MADRS scores ( −20.1 for mirtazapine and −17.5 for venlafaxine ) and HAM-D-17 scores ( −17.1 for mirtazapine and −14.6 for venlafaxine ) at the end of the treatment . Although not statistically significant , at all assessment times higher percentages of patients treated with mirtazapine were classified as responders ( ≥50 % reduction ) on the HAM-D ( at endpoint , 62 % vs. 52 % ) and MADRS ( at endpoint : 64 % vs. 58 % ) . Likewise were the percentages of remitters ( HAM-D score ≤7 ; MADRS score ≤12 ) also higher in the mirtazapine group . A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points ( p ≤ 0.03 ) . Both treatments were well tolerated . Although slightly more subjects treated with mirtazapine reported at least one adverse event , a statistically significantly higher percentage of patients treated with venlafaxine ( 15.3 % ) than mirtazapine ( 5.1 % ) dropped out because of adverse events ( p = 0.037 ) . Quality of life improved in both treatment groups . In this study , treatment with mirtazapine result ed in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events & NA ; A 24‐week , double‐blind , r and omized trial was performed to compare the efficacy and tolerability of venlafaxine and paroxetine in patients with major depression or dysthymia . Out patients aged 18‐70 years with a baseline score of 17 on the 21‐item Hamilton Depression Rating Scale ( HAM‐D ) were eligible . Patients were r and omly assigned to venlafaxine , 37.5 mg , in the morning and evening or paroxetine , 20 mg , in the morning and placebo in the evening , which could be increased to venlafaxine , 75 mg twice daily , or paroxetine , 20 mg twice daily , after 4 weeks . Efficacy was assessed with the 21‐item HAM‐D , the Montgomery‐Asberg Rating Scale , the Hamilton Anxiety Rating Scale , and the Clinical Global Impressions Scale . Forty‐one patients were r and omized to venlafaxine and 43 to paroxetine . At week 6 , a response was observed in 55 % of patients on venlafaxine and 29 % on paroxetine ( P = 0.03 ) . At week 12 , significantly ( P = 0.011 ) more patients in the venlafaxine group had a HAM‐D remission score of 8 or less ( 59 % versus 31 % ) . Discontinuation for any reason occurred in 16 ( 39 % ) patients on venlafaxine and 11 ( 26 % ) on paroxetine . The most common adverse events were nausea ( 28 % ) , headache ( 18 % ) and dry mouth ( 15 % ) with venlafaxine and headache ( 40 % ) and constipation ( 16 % ) with paroxetine . Venlafaxine was effective and well tolerated for the treatment of patients with mild to moderate depression or dysthymia . A consistently higher proportion of patients had a response or remission on venlafaxine than on paroxetine 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 The objective of this study was to compare venlafaxine and fluoxetine with placebo in treating major depressive disorder with melancholic features . Adult in patients with Diagnostic and Statistical Manual of Mental Disorders , fourth edition major depressive disorder with melancholia and 21-item Hamilton Depression Rating Scale ( HAM-D21 ) scores ≥24 ( n=289 ) were r and omized to receive ( double-blind ) venlafaxine 225–375 mg/day , fluoxetine 60–80 mg/day , or placebo for 6 weeks . The primary outcome measures were HAM-D21 total score , HAM-D depressed mood item , Montgomery Åsberg Depression Rating Scale total score and the Clinical Global Impressions-Severity ( CGI-S ) and Improvement ( CGI-I ) scores . Last observation carried forward ( LOCF ) was the primary analysis method . In the LOCF analysis , venlafaxine was statistically superior to placebo on the CGI-S ( venlafaxine −1.7 , placebo −1.1 ; P=0.003 ) and the HAM-D depressed mood item ( venlafaxine −1.6 , placebo −1.1 ; P=0.010 ) ; and to fluoxetine on the CGI-S ( −1.2 ; P=0.012 ) . No significant differences were observed on the other 12 LOCF primary efficacy comparisons . Increases in pulse and blood pressure , dry mouth , constipation , and lightheadedness were significantly more common with venlafaxine than fluoxetine . Venlafaxine was statistically superior to placebo on two of five primary and two of five secondary outcome measures and to fluoxetine on one primary and one secondary outcome measure ( LOCF ) . Venlafaxine was not superior to fluoxetine or placebo in providing remission BACKGROUND Hypersomnia is a cardinal symptom of seasonal affective disorder/winter depression . This open-label pilot study assessed modafinil , a novel wake-promoting agent , as treatment for seasonal affective disorder/winter depression . METHODS Total daily modafinil dose was 100 mg ( all patients week 1 ) , and 100 mg or 200 mg split dose ( weeks 2 - 8 ) . Efficacy assessment s ( weeks 1 , 2 , 5 , and 8) included the Structured Interview Guide for the Hamilton Depression ( HAM-D ) Rating Scale , Seasonal Affective Disorder Version ( SIGH-SAD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression of Change ( CGI-C ) , Fatigue Severity Scale ( FSS ) , and Epworth Sleepiness Scale ( ESS ) . RESULTS Thirteen patients ( 11 women ; mean age , 41 years ) were enrolled , 12 were evaluable for efficacy ( 100 mg dose , five patients ; 200 mg dose , seven patients ) , and nine completed treatment . Modafinil significantly improved winter depression as shown by reductions from baseline in mean SIGH-SAD at week 1 ( P<0.01 ) through week 8 ( P<0.001 weeks 2 - 8 ) and MADRS total scores from week 2 through week 8 ( P<0.01 for all ) . At week 8 , mean SIGH-SAD total score was 17.1 ( versus 37.2 at baseline , P<0.001 ) , and mean MADRS total score was 13.3 ( versus 26.9 at baseline , P<0.01 ) . Modafinil significantly improved overall clinical condition at all time points ( P<0.001 ) . The response rate was 67 % on the SIGH-SAD ( 29 item ) , HAM-D ( 21 item ) , and MADRS , and 100 % on eight atypical SIGH-SAD items . Modafinil significantly reduced fatigue ( FSS ) and improved wakefulness ( ESS ) from weeks 2 through 8 ( P<0.01 ) . Modafinil was well tolerated . LIMITATIONS This was an open-label , single site study . CONCLUSIONS Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression Escitalopram , the S‐enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor ( SSRI ) has been shown to be efficacious in the treatment of major depression in white population s. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression . Patients who met DSM‐IV criteria for a major depressive episode were enrolled in this multicenter , r and omized , double‐blind , fixed‐dose comparison trial . Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks . All patients were assessed with the 17‐item Hamilton Depression Rating Scale ( HAM‐D‐17 ) and the Montgomery – Åsberg Depression Rating Scale ( MADRS ) . Tolerability was assessed on the basis of adverse effects ( measured with a locally developed checklist ) , regular biochemical tests , and electrocardiograph ( ECG ) assessment s. Two hundred forty patients were enrolled and r and omized to escitalopram ( 123 patients ) or fluoxetine ( 117 patients ) . The HAM‐D‐17 total scores of both groups decreased significantly from baseline , but there was no significant difference at week 8 between the two groups ( 15.8 for escitalopram and 14.7 for fluoxetine ; P > .05 ) . There were no significant differences in response rates at all visits after treatment based on either HAM‐D‐17 or MADRS . A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM‐D‐17 : “ depressed mood ” ( P = .023 ) and “ work and interest ” ( P = .024 ) . The adverse events reported in the escitalopram and fluoxetine groups were comparable , and most were mild to moderate . Both drugs showed good compliance profiles . Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression , with possible superiority in some core symptoms such as “ depressed mood ” and “ work and interest . ” Depression and Anxiety 0:1–9 , 2006 . © 2006 Wiley‐Liss , OBJECTIVE Dialogues Time to Talk ( Dialogues ) is a care management program that provides additional follow-up care and patient education for out patients with major depressive disorder ( MDD ) starting venlafaxine extended release ( ER ) therapy .  This study examined the effect of the Dialogues program on patient treatment satisfaction . METHODS In this 6-month , open-label study , primary care patients with MDD received usual care and were r and omly assigned to venlafaxine ER ( 75 to 225 mg/d ) either alone or in combination with the Dialogues program ( venlafaxine ER + D ) . The primary outcome was patient treatment satisfaction on day 112 , measured by the 10- point Satisfaction with Depression Care Scale ( SDCS ) . Secondary efficacy outcomes included the 17-item Hamilton Rating Scale for Depression ( HAM-D17 ) total score , response ( ≥50 % decrease from baseline HAM-D17 score ) , and remission ( HAM-D17 ≤ 7 ) . RESULTS The modified intent-to-treat population included 263 patients in the venlafaxine ER group and 257 in the venlafaxine ER+D group . The percentage of patients with an SDCS " very satisfied " score ( ≥8 ) at day 112 was not significantly different in the venlafaxine ER and venlafaxine ER+D groups ( 63 % and 58 % , respectively ; P = 0.22 ) . No significant differences were found on any secondary outcomes . CONCLUSION Among primary care patients starting venlafaxine  ER for MDD , participation in the Dialogues program did not have a statistically significant effect on patient treatment satisfaction BACKGROUND Major depressive disorder ( MDD ) is a common , chronic illness associated with substantial disability and economic burden . Although a number of effective antidepressants are available , the need for new medications that are effective and well tolerated remains . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/d with placebo for MDD . A post hoc pooled analysis was conducted to evaluate this study in the context of all similarly design ed , completed studies with the 2 doses . METHODS This was an 8-week , Phase III , r and omized , double-blind , duloxetine-referenced , placebo-controlled , parallel-group trial conducted in 21 centers across the United States .  Duloxetine was included for assay sensitivity as a positive control ; the study was not design ed or powered to compare desvenlafaxine with duloxetine .  Participants were out patients aged > or = 18 years with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition-defined MDD and a 17-item Hamilton Rating Scale for Depression ( HAM-D(17 ) ) score > or = 20 . Patients were r and omly assigned at baseline to fixed-dose desvenlafaxine ( 50 or 100 mg/d ) , fixed-dose duloxetine ( 60 mg/d ) , or placebo . The primary outcome measure was HAM-D(17 ) total score at the final evaluation . Additional measures included the Clinical Global Impressions-Improvement ( CGI-I ) score , Montgomery Asberg Depression Rating Scale ( MADRS ) score , Clinical Global Impressions-Severity ( CGI-S ) score , and 6-item Hamilton Rating Scale for Depression , Bech version ( HAM-D(6 ) ) . Tolerability assessment s included discontinuation rates , adverse events ( AEs ) , vital signs , and laboratory tests . The post hoc pooled analysis was performed using data from the current study and 2 previously published , positive studies that compared the efficacy and tolerability of desvenlafaxine 50 and 100 mg/d with placebo for MDD . The design and method ologies of the 2 studies were similar to the methodology of the current trial , other than not including a reference compound . RESULTS Of the 925 patients who were screened , 287 did not meet entry criteria , and 638 patients enrolled in the study ; the intent-to-treat ( ITT ) population included 615 patients who were evaluated for efficacy ( mean [ SD ] age range , 38.8 - 40.7 [ 12.1 - 13.2 ] years ; mean weight range , 83.3 - 87.0 [ 22.8 - 23.9 ] kg ; female sex , 398 [ 64.7 % ] ; white race , 458 [ 74.5 % ] ) . The primary end point did not reach significance based on the global F test for controlling multiplicity of the desvenlafaxine doses . Based on pairwise comparison , significantly greater improvements on the HAM-D(17 ) were observed in the desven-lafaxine 100 mg/d ( -10.5 ; P = 0.028 , unadjusted for multiple comparisons ) and duloxetine 60 mg/d groups ( -10.3 ; P = 0.047 ) compared with placebo ( -8.7 ) . Desvenlafaxine 100 mg/d and duloxetine 60 mg/d were associated with significantly better scores compared with placebo on the CGI-I , MADRS , CGI-S , and HAM-D(6 ) . No significant differences were observed in any scale between the desvenlafaxine 50 mg/d and placebo groups . Discontinuation rates due to AEs were 5 % , 7 % , 13 % , and 6 % for the desvenlafaxine 50-mg/d , desvenlafaxine 100-mg/d , duloxetine 60-mg/d , and placebo groups , respectively . The ITT population from all 3 studies in the pooled analysis consisted of 1388 patients ( mean [ SD ] age range , 38.8 - 45.7 [ 12.1 - 12.6 ] years ; mean weight range , 73.1 - 87.0 [ 17.6 - 23.9 ] kg ; female sex , 896 [ 64.6 % ] ; white race , 1136 [ 81.8 % ] ) . Significantly greater improvements on the HAM-D(17 ) were observed for desvenlafaxine 50 mg/d ( -11.5 ; P < 0.001 ) and 100 mg/d ( -11.8 ; P < 0.001 ) versus placebo ( -9.6 ) . Both doses were significantly better than placebo on the CGI-I , MADRS , and HAM-D(6 ) . CONCLUSIONS The current study failed to meet its primary efficacy end point based on the a priori analysis plan . Desvenlafaxine was generally well tolerated . A post hoc pooled analysis of this trial and 2 previously published trials with both desvenlafaxine 50 and 100 mg/d found both doses to be effective for MDD compared with placebo . Clinical Trials.gov Identifier : 00384033 Background : Due to the clinical challenges of treatment-resistant depression ( TRD ) , we evaluated the efficacy of mindfulness-based cognitive therapy ( MBCT ) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual ( TAU ) pharmacotherapy in TRD . Methods : This single-site , r and omized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program ( HEP ) , comprising physical fitness , music therapy and nutritional education , as adjuncts to TAU pharmacotherapy for outpatient adults with TRD . The primary outcome was change in depression severity , measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale ( HAM-D17 ) , with secondary depression indicators of treatment response and remission . Results : We enrolled 173 adults ; mean length of a current depressive episode was 6.8 years ( SD = 8.9 ) . At the end of 8 weeks of treatment , a multivariate analysis showed that relative to the HEP condition , the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 ( 36.6 vs. 25.3 % ; p = 0.01 ) and a significantly higher rate of treatment responders ( 30.3 vs. 15.3 % ; p = 0.03 ) . Although numerically superior for MBCT than for HEP , the rates of remission did not significantly differ between treatments ( 22.4 vs. 13.9 % ; p = 0.15 ) . In these models , state anxiety , perceived stress and the presence of personality disorder had adverse effects on outcomes . Conclusions : MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates . MBCT appears to be a viable adjunct in the management of TRD BACKGROUND Paroxetine is a potent and selective serotonin reuptake inhibitor ( SSRI ) . The present study assessed the efficacy and tolerability of paroxetine against placebo in depressed out patients . METHOD A double-blind , parallel-group study was undertaken in four st and -alone centers . Patients aged 18 - 65 years , meeting DSM-III criteria for major depression , and having a Hamilton Rating Scale for Depression ( HAM-D ) score > or = 18 on the first 17 items of the HAM-D-21 were r and omized to paroxetine or placebo for 6 weeks of treatment . Efficacy outcome variables included the HAM-D , the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impressions Scale ( CGI ) , and the Covi Anxiety Scale . Tolerability was assessed by asking a non-leading question . Routine laboratory safety and vital sign data from all four centers were pooled . The primary analysis used the intention-to-treat sample and for efficacy variables the last-observation-carried-forward data set was employed . Statistical methods included one-way analysis of variance for parametric and Fisher exact test for nonparametric variables . RESULTS Significant differences ( p < or = .05 ) were found between paroxetine and placebo on the HAM-D and CGI by Week 2 and on all efficacy outcome variables by Week 4 . Improvement on the HAM-D sleep factor occurred 2 weeks prior to that seen on the retardation factor . Similar results were obtained when an adequate treatment group ( therapy for > or = 28 days ) was considered . A full clinical response ( CGI-severity of illness score 1 or 2 ) was seen in over 40 % of subjects . Adverse events were more common for paroxetine compared with placebo ( p < or = .01 ) . Somnolence was twice more common than nervousness . Dropout due to adverse events was similar between therapies . Paroxetine had no clinical ly significant effect on laboratory safety data or vital signs . CONCLUSION Paroxetine was an effective , well tolerated , and safe antidepressant . Side effects were typical of the SSRI class of drugs . Symptoms indicative of a nonalerting profile were more common than those associated with alerting effects BACKGROUND There are few published placebo-controlled clinical trials demonstrating the efficacy of the newer antidepressants in markedly or severely depressed hospitalized patients . This study demonstrates the efficacy of nefazodone compared with placebo in the treatment of patients hospitalized for major depression . METHOD Nefazodone and placebo treatment were compared in a 6-week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression ( without psychosis ) at 2 study centers .  Efficacy was evaluated using st and ard psychiatric rating scales , and patients were monitored for safety . RESULTS Nefazodone treatment result ed in a significant reduction ( p < .01 ) of the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score compared with placebo from the end of the first treatment week through the end of the study ( -12.2 nefazodone vs. -7.7 placebo ) . At the end of the trial , significantly more nefazodone-treated patients ( 50 % ) than placebo-treated patients ( 29 % ) had responded , as indicated by their Clinical Global Impressions-Improvement score ( p = .021 ) or by a > or = 50 % reduction in their HAM-D-17 scores ( p = .017 ) . Significantly more patients treated with nefazodone ( 36 % ) than placebo-treated patients ( 14 % ) had a HAM-D-17 score < or = 10 at the end of treatment ( p = .004 ) . Significant treatment differences ( p < .01 ) in favor of nefazodone were also seen in the Montgomery-Asberg Depression Rating Scale ; the HAM-D retardation , anxiety , and sleep disturbance factors ; and HAM-D item 1 ( depressed mood ) . Patients with dysthymia in addition to major depression  also showed significant improvement ( p < .05 ) when treated with nefazodone , with significant differences in response rates seen as early as week 2 and through the end of the trial . The mean  nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of treatment . Nefazodone was well tolerated , and the number of patients discontinuing owing to adverse events was small , with no significant safety issues noted in either treatment group . Fewer nefazodone-treated than placebo-treated patients discontinued owing to lack of efficacy . CONCLUSION Nefazodone was superior to placebo in the treatment of marked to severe major depression in patients requiring hospitalization . The clinical benefit of nefazodone was evident as early as the first week of treatment as judged by several measures of efficacy , with significant differences from placebo sustained throughout the trial
Conclusions : According to the published literature , the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS .
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 ) .