Placebo-controlled inpatient comparison of venlafaxine and fluoxetine for the treatment of major depression with melancholic features Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. Differential Antidepressant Symptom Efficacy: Placebo-Controlled Comparisons of Duloxetine and SSRIs (Fluoxetine, Paroxetine, Escitalopram) Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study* A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder. Escitalopram and duloxetine in major depressive disorder: a pharmacoeconomic comparison using UK cost data. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Double-Blind Comparison of Escitalopram and Duloxetine in the Acute Treatment of 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.
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 The aim of the present paper was to compare the efficacy and safety of duloxetine with paroxetine in the acute treatment of major depressive disorder ( MDD ) . In a r and omized , double-blind trial of 8 weeks active treatment , patients with non-psychotic MDD were r and omized to duloxetine 60 mg ( n = 238 ) or paroxetine 20 mg ( n = 240 ) once daily . Efficacy was primarily measured on change in the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) using a non-inferiority test with a margin of 2.2 . Secondary efficacy measures included the HAMD(17 ) subscales , Hamilton Rating Scale for Anxiety , Clinical Global Impressions-Severity , Patient Global Impressions-Improvement , Somatic Symptoms Inventory and Visual Analog Scales ( VAS ) for pain . Safety measures included treatment-emergent adverse events ( TEAE ) , vital signs , weight , laboratory analyses and electrocardiograms . Non-inferiority of duloxetine to paroxetine was demonstrated because the upper bound of the confidence interval for mean difference in HAMD(17 ) change ( 0.71 ) was less than the non-inferiority margin . Secondary efficacy end-points did not differ significantly between treatments with the exception of VAS back pain , where the pooled mean was lower in the duloxetine group ( 17.1 ) compared with the paroxetine group ( 20.3 , P = 0.048 ) . No significant differences were observed in the number of early discontinuations and overall TEAE . However , significantly greater proportions of patients in the duloxetine group experienced nausea and palpitations . No clinical ly relevant changes in laboratory values , vital signs , weight or electrocardiograms were observed with either treatment . The present study verifies the utility of duloxetine as an efficacious and safe treatment for both emotional and physical symptoms of MDD in this predominantly Asian patient sample BACKGROUND Duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , was evaluated for therapeutic efficacy and safety/tolerability in the treatment of major depression . METHOD In an 8-week multicenter , double-blind , placebo-controlled study , 173 patients ( aged 18 - 65 years ) with DSM-IV major depressive disorder were r and omly allocated to receive placebo ( N = 70 ) , duloxetine ( N = 70 ) , or fluoxetine , 20 mg q.d . ( N = 33 ) . Duloxetine dose was titrated in the first 3 weeks in a forced-titration regimen from 40 mg ( 20 mg b.i.d . ) to 120 mg/day ( 60 mg b.i.d . ) . Patients were required to have a Clinical Global Impressions (CGI)-Severity of Illness scale score of at least moderate severity ( > or = 4 ) and a 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score of at least 15 . Patients could not have had any current primary DSM-IV Axis I diagnosis other than major depressive disorder , or any anxiety disorder as a primary diagnosis within the past year , excluding specific phobias . The primary efficacy measurement was the HAM-D-17 total score , and secondary measures included the Montgomery-Asberg Depression Rating Scale , CGI-Severity of Illness and CGI-Improvement , and Patient Global Impression of Improvement . Safety was evaluated by recording the occurrence of discontinuation rates and treatment-emergent adverse events and by measurement of vital signs and laboratory analytes . RESULTS Duloxetine was superior to placebo in change on the HAM-D-17 ( p = .009 ) . Estimated probabilities of response and remission were 64 % and 56 % , respectively , for duloxetine , compared with 52 % and 30 % for fluoxetine and 48 % and 32 % for placebo . Duloxetine was numerically superior to fluoxetine on the primary and most of the secondary outcome measures . In general , duloxetine was well tolerated ; 76 % of patients achieved the maximum dose , and insomnia and asthenia were the only adverse events reported statistically significantly ( p < .05 ) more frequently by duloxetine-treated patients compared with placebo-treated patients . CONCLUSION These data indicate that duloxetine is efficacious for the treatment of major depressive disorder and is well tolerated and safe Objective : To test the hypothesis that in patients with major depressive disorder ( MDD ) , the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors ( SSRIs ) and that patterns of response will differ based on symptom severity at baseline . Method : Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD : 7 r and omized , double-blind , fixed-dose , 8-week studies of duloxetine  ( n = 1,133 )  versus SSRI  ( n = 689 )  versus placebo  ( n = 641 ) .  Duloxetine doses were 40 , 60 , 80 and 120 mg/day . SSRI doses were 10 mg/day ( escitalopram ) and 20 mg/day ( fluoxetine and paroxetine ) . Results : Compared to SSRI-treated patients , duloxetine-treated patients had a significantly greater ( p ≤ 0.05 ) reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score and HAMD17 items of work and activities , psychomotor retardation , genital symptoms and hypochondriasis . Differences favoring the SSRIs approached significance for middle insomnia ( p = 0.057 ) and late insomnia ( p = 0.06 ) , with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine . Similarly , the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms ( p = 0.056 ) , with an effect size twice that observed for the SSRIs . The HAMD17 total score difference was driven mostly by patients with lower baseline MDD severity ( HAMD17 total score ≤19 ) , where the HAMD17 effect size advantage for duloxetine over combined SSRIs was statistically significant ( p = 0.031 ) . Conclusion : Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity , and different HAMD17 items responded differently to duloxetine compared with SSRIs . Underst and ing these differences may be useful in tailoring antidepressant therapy for individual patients CONTEXT The high percentage of failed clinical trials in depression may be due to high placebo response rates and the failure of st and ard statistical approaches to capture heterogeneity in treatment response . OBJECTIVE To assess whether growth mixture modeling can provide insights into antidepressant and placebo responses in clinical trials of patients with major depression . DESIGN We reanalyzed clinical trials of duloxetine to identify distinct trajectories of Hamilton Scale for Depression ( HAM-D ) scores during treatment . We analyzed the trajectories in the entire sample and then separately in all active arms and in all placebo arms . Effects of duloxetine hydrochloride , selective serotonin reuptake inhibitor ( SSRI ) , and covariates on the probability of following a particular trajectory were assessed . Outcomes in different trajectories were compared using mixed-effects models . SETTING Seven r and omized double-blind clinical trials of duloxetine vs placebo and comparator SSRI . Patients A total of 2515 patients with major depression . INTERVENTIONS Duloxetine and comparator SSRI . Main Outcome Measure Total score on the HAM-D. RESULTS In the entire sample and in the antidepressant-treated sub sample , we identified trajectories of responders ( 76.3 % of the sample ) and nonresponders ( 23.7 % of the sample ) . However , placebo-treated patients were characterized by a single response trajectory . Duloxetine and SSRI did not differ in efficacy , and compared with placebo they significantly decreased the odds of following the nonresponder trajectory . Antidepressant responders had significantly better HAM-D scores over time than placebo-treated patients , but antidepressant nonresponders had significantly worse HAM-D scores over time than the placebo-treated patients . CONCLUSIONS Most patients treated with serotonergic antidepressants showed a clinical trajectory over time that is superior to that of placebo-treated patients . However , some patients receiving these medications did more poorly than patients receiving placebo . These data highlight the importance of ongoing monitoring of medication risks and benefits during serotonergic antidepressant treatment . They should further stimulate the search for biomarkers or other predictors of responder status in guiding antidepressant treatment OBJECTIVE Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder ( MDD ) . METHODS In this r and omized , double-blind trial , patients age > or = 18 meeting DSM-IV criteria for MDD were r and omized to placebo ( N=99 ) , duloxetine 80 mg/day ( N=93 ) , duloxetine 120 mg/day ( N=103 ) , or paroxetine 20 mg/day ( N=97 ) . The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression ( HAMD(17 ) ) total score after 8 weeks of treatment ; a number of secondary efficacy measures also were assessed . Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events ( TEAEs ) , vital signs , and weight . The Arizona sexual experiences scale was used to assess sexual functioning . Patients who had a > or = 30 % reduction from baseline in the HAMD(17 ) total score  at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase ; efficacy and safety/tolerability outcomes were assessed during continuation treatment . RESULTS More than 87 % of patients completed the acute phase in each treatment group . Duloxetine-treated patients ( both doses ) showed significantly greater improvement ( P<0.05 ) in the HAMD(17 ) total score at week 8 compared with placebo . Paroxetine was not significantly different from placebo ( P=0.089 ) on mean change on the HAMD(17 ) .  Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures ( six of nine ) compared with placebo while duloxetine 80 mg/day ( three of nine ) and paroxetine ( three of nine ) were significantly superior to placebo on fewer secondary measures . HAMD(17 ) mean change data from this study and an identical sister study were pooled as defined a priori for the purpose s of performing a non-inferiority test versus paroxetine . Both duloxetine doses met statistical criteria for non-inferiority to paroxetine .  TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases . CONCLUSIONS The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated . Tolerability , as measured by TEAEs , and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children ( 7 - 11 years ) and adolescents ( 12 - 17 years ) with major depressive disorder ( MDD ) . METHODS Patients ( n=337 ) in this 36 week study ( 10 week acute and 26 week extension treatment ) received duloxetine ( 60 - 120 mg once daily [ QD ] , n=117 ) , fluoxetine ( 20 - 40 mg QD , n=117 ) , or placebo ( n=103 ) . Measures included : Children 's Depression Rating Scale-Revised ( CDRS-R ) , treatment-emergent adverse events ( TEAEs ) , and Columbia-Suicide Severity Rating Scale ( C-SSRS ) . RESULTS Neither active drug ( duloxetine or fluoxetine ) separated significantly ( p<0.05 ) from placebo on mean change from baseline to end-point ( 10 weeks ) on the CDRS-R total score . There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs ( SAEs ) , total TEAEs , or discontinuation for AE during acute treatment . There were no completed suicides or deaths , and no clinical ly significant electrocardiogram ( ECG ) abnormalities observed during the study . One fluoxetine and one duloxetine patient experienced alanine aminotransferase ( ALT ) three or more times the upper limit of normal , which resolved during the study . A total of 8 ( 7.1 % ) duloxetine patients , 7 ( 6.8 % ) placebo patients , and 9 ( 8.0 % ) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment . Of the patients with suicidal ideation at baseline , 15/19 ( 79 % ) duloxetine , 19/19 ( 100 % ) placebo , and 16/19 ( 84 % ) fluoxetine had improvement in suicidal ideation at end-point during acute treatment . One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study . CONCLUSION Trial results were inconclusive , as neither the investigational drug ( duloxetine ) nor the active control ( fluoxetine ) separated from placebo on the CDRS-R at 10 weeks . No new duloxetine safety signals were identified relative to those seen in adults . Clinical Trial Registry Number : NCT00849901 OBJECTIVE Various classes of antidepressant medications generally induce remission of major depressive disorder  in only about one-third of patients . In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation , the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone . In this double-blind study , the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation . METHOD Patients ( N=105 ) meeting DSM-IV criteria for major depressive disorder were r and omly assigned to receive , from treatment initiation , either fluoxetine monotherapy ( 20 mg/day ) or mirtazapine ( 30 mg/day ) in combination with fluoxetine ( 20 mg/day ) , venlafaxine ( 225 mg/day titrated in 14 days ) , or bupropion ( 150 mg/day ) for 6 weeks . The primary outcome measure was the Hamilton Depression Rating Scale ( HAM-D ) score . RESULTS The overall dropout rate was 15 % , without notable differences among the four groups . Compared with fluoxetine monotherapy , all three combination groups had significantly greater improvements on the HAM-D. Remission rates ( defined as a HAM-D score of 7 or less ) were 25 % for fluoxetine , 52 % for mirtazapine plus fluoxetine , 58 % for mirtazapine plus venlafaxine , and 46 % for mirtazapine plus bupropion . Among patients who had a marked response , double-blind discontinuation of one agent produced a relapse in about 40 % of cases . CONCLUSIONS The combination treatments were as well tolerated as fluoxetine monotherapy and more clinical ly effective . The study results , which add to a growing body of evidence , suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication ABSTRACT Objective : The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment1 . The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine ( a dual serotonin and norepinephrine reuptake inhibitor ) and escitalopram ( a selective serotonin reuptake inhibitor ) . Research design and methods : This was a r and omized , double-blind , placebo- and active comparator-controlled study , in which patients ( ≥ 18 years ) meeting DSM‑IV criteria for Major Depressive Disorder ( MDD ) received duloxetine 60 mg once daily ( QD ; N = 273 ) , escitalopram 10 mg QD ( N = 274 ) , or placebo ( N = 137 ) for 8 weeks . The primary objective was to compare the onset of antidepressant efficacy , by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group . Main outcome measures : Onset of efficacy was defined as a 20 % decrease from baseline on the 17‑item Hamilton Rating Scale for Depression ( HAMD17 ) Maier subscale that was maintained or exceeded at all subsequent visits . Results : Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6 % versus 35.2 % , respectively ( treatment difference = 7.4 % ; 95 % confidence interval , –1.3 % to 16.2 % ; p = 0.097 ) . Both drugs showed significant improvement compared with placebo ( p ≤ 0.05 ) on the primary efficacy measure ( Maier subscale ) at Week 1 and endpoint ( Week 8) . No differences were found between duloxetine , escitalopram , and placebo rates of remission or response at 8 weeks . Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea , dry mouth , vomiting , yawning , and irritability . The rate of discontinuation due to adverse events did not differ significantly between treatment groups . Limitations : Given the difficulties in constructing appropriate dose comparisons , the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole . This study employed a fixed-dose design ; flexible-dose design s are more likely to find a difference between antidepressants and placebo . Conclusion : In this study , both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8‑week acute treatment period , while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks . Escitalopram at a starting dose of 10 mg QD was better tolerated  than duloxetine at a starting dose of 60 mg QD . This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram  in antidepressant onset efficacy , and the results show that duloxetine is at least as fast as ( non-inferior to ) escitalopram . Trial registration : Clinical Trials.gov identifier : NCT00073411 Based on preliminary evidence of its usefulness in treatment-resistant depression ( TRD ) , an olanzapine/fluoxetine combination ( OFC ) was examined in comparison with olanzapine , fluoxetine , and venlafaxine in a TRD population . In this 12-week double-blind study , 483 subjects with unipolar , nonpsychotic TRD , with historic failure on a selective serotonin reuptake inhibitor ( SSRI ) and prospect i ve failure on open-label venlafaxine , were r and omized to an OFC or to an olanzapine , fluoxetine , or venlafaxine monotherapy group . Venlafaxine was continued r and omly in the double-blind acute phase to explore the benefits of continuation versus switching therapy . The Montgomery-Asberg Depression Rating Scale ( MADRS ) total change score at end point was the primary outcome measure . The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment ( MADRS mean change = -7.2 , baseline = 29.6 ) , in comparison to olanzapine ( -4.8 , P=.03 ) , fluoxetine ( -4.7 , P=.03 ) , or venlafaxine ( -3.7 , P=.002 ) groups and maintained its statistical separation from all three monotherapy groups through week 6 . At end point , the OFC group was significantly different only from the olanzapine group ( -14.1 vs. -7.7 , P<.001 ) . Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode ( n=334 ) revealed statistical separation from both olanzapine and fluoxetine ( but not venlafaxine ) at end point : OFC ( -14.6 ) versus olanzapine ( -9.4 , P<.001 ) versus fluoxetine ( -10.7 , P=.006 ) versus venlafaxine ( -14.7 , P=.98 ) . The OFC had a safety profile comparable to its component monotherapies ( i.e. , olanzapine and fluoxetine ) , showed a rapid onset of antidepressant effect , and was effective in this TRD sample . At the study end point , OFC , fluoxetine , venlafaxine , and low-dose OFC all appeared to be similarly effective This double-blind , placebo-controlled study compared venlafaxine ( immediate release ) , the first modern serotonin-norepinephrine reuptake inhibitor , with the selective serotonin reuptake inhibitor fluoxetine .  Out patients were r and omly assigned to 6 weeks of treatment with venlafaxine  ( 75 - 225mg/day ; n=102 ) , fluoxetine ( 20 - 60mg/day ; n=104 ) , or placebo ( n=102 ) . Efficacy was assessed using the 21-item Hamilton Depression Rating Scale ( HAM-D(21 ) ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression-Severity of Illness ( CGI-S ) scale , response and remission rates , and several other measures . Intent-to-treat analyses utilized both the last observation carried forward and ETRANK methods to account for missing data . At week 6 or study endpoint , venlafaxine ( mean dose : 142mg/day ) was superior to placebo on most outcomes measures , whereas the differences between fluoxetine ( mean dose : 41mg/day ) and placebo were less consistent . Final remission ( defined as HAM-D < or = 7 ) rates were 32 % , 28 % , and 22 % for venlafaxine , fluoxetine , and placebo , respectively . Few differences between the active treatments attained statistical significance . Both active therapies were generally well tolerated ; however , attrition due to adverse events , incidence of selected side effects , and increases in pulse and blood pressure favored fluoxetine over venlafaxine . This study provides further evidence that venlafaxine is effective after 6 weeks of treatment compared with placebo . The efficacy profile of fluoxetine was somewhat less consistent . It is strongly recommended that future studies of comparative antidepressant efficacy be adequately powered to detect modest between-drug differences in efficacy The efficacy and tolerability of Lu AA21004 at 5 mg/day , a novel multimodal antidepressant , were assessed in elderly patients with recurrent major depressive disorder . Patients were r and omly assigned ( 1 : 1 : 1 ) to Lu AA21004 5 mg/day , duloxetine 60 mg/day ( reference ) or to placebo in an 8-week double-blind study . The primary efficacy measure was the 24-item Hamilton Depression Scale ( HAM-D24 ) total score ( analysis of covariance , last observation carried forward ) . Patients ( mean age 70.6 years ) had a mean baseline HAM-D24 score of 29.0 .  Lu AA21004 showed significantly ( P=0.0011 ) greater improvement on the primary efficacy endpoint compared with placebo at week 8 ( 3.3 points ) . Duloxetine also showed superiority to placebo at week 8 , thereby validating the study . HAM-D24 response ( 53.2 vs. 35.2 % ) and HAM-D17 remission ( 29.2 vs. 19.3 % ) rates at endpoint were higher for Lu AA21004 than for placebo . Lu AA21004 showed superiority to placebo in cognition tests of speed of processing , verbal learning and memory . The withdrawal rate due to adverse events was 5.8 % ( Lu AA21004 ) , 9.9 % ( duloxetine ) and 2.8 % ( placebo ) . Whereas nausea was the only adverse event with a significantly higher incidence on treatment with Lu AA21004 ( 21.8 % ) compared with placebo ( 8.3 % ) , the incidence of nausea , constipation , dry mouth , hyperhidrosis and somnolence was higher for duloxetine . In conclusion , Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder BACKGROUND A subset of patients with comorbid major depressive disorder and generalized anxiety disorder ( GAD ) was examined from a double-blind . placebo-controlled study comparing the efficacy and safety of venlafaxine extended release ( XR ) and fluoxetine . METHOD From a total of 368 patients , 92 patients meeting DSM-IV criteria for major depressive disorder who also had comorbid GAD were identified . The comparison group comprised 276 evaluable noncomorbid patients . Patients received venlafaxine XR ( 75 - 225 mg/day ) , fluoxetine ( 20 - 60 mg/day ) , or placebo for 12 weeks . Efficacy evaluations included Hamilton Rating Scale for Depression ( HAM-D ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions ( CGI ) scale . RESULTS By the final assessment at week 12 , comorbid patients in the venlafaxine XR group , but not in the fluoxetine group , showed a significantly greater decrease than those in the placebo group in the primary efficacy variables of mean HAM-D and HAM-A total scores ( p < .05 , pairwise comparison ) . In comorbid patients , significant pairwise differences were noted between venlafaxine XR and placebo at week 12 for the secondary variables of HAM-D anxiety-somatization and retardation factors , HAM-D depressed mood item . HAM-A psychic anxiety factor , the Hospital Anxiety and Depression scale ( HAD ) anxiety subscale score , and the Covi Anxiety Scale score . Fluoxetine was significantly different from placebo only on the HAD depression subscale score . Response , defined as > or = 50 % decrease in symptoms score , was achieved in 66 % and 59 % of the comorbid patients for HAM-D and HAM-A , respectively , in the venlafaxine XR group at week 12 . This response was higher than that seen with fluoxetine ( 52 % and 45 % ) or placebo ( 36 % and 24 % ) . Onset of efficacy appeared to be slower in comorbid than in noncomorbid patients . CONCLUSION This is the first evidence from a controlled study of the effectiveness of pharmacotherapy in patients with comorbid major depressive disorder and GAD . The delayed improvement in comorbid patients compared with noncomorbid patients suggests that a longer treatment period may be necessary in comorbid patients BACKGROUND Selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-noradrenaline reuptake inhibitors ( SNRIs ) are approved for the treatment of major depressive disorder ( MDD ) . The allosteric SSRI escitalopram has been shown to be at least as clinical ly effective as the SNRIs venlafaxine and duloxetine in MDD , with a better tolerability profile . In addition , escitalopram has been shown to be cost saving compared with venlafaxine . OBJECTIVE To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD , and to identify key cost drivers . METHODS The pharmacoeconomic evaluation was conducted alongside a 24-week , double-blind , multinational r and omized study ( escitalopram 20 mg/day and duloxetine 60 mg/day ) in out patients with MDD , aged 18 - 65 years , with Montgomery-Asberg Depression Rating Scale ( MADRS ) score > or=26 and Clinical Global Impression Severity ( CGI-S ) score > or=4 , and baseline duration of the current depressive episode of 12 weeks to 1 year . The analysis was conducted on the full analysis set ( FAS ) , which included all patients with > or=1 valid post-baseline health economic assessment . Effectiveness outcomes of the cost-effectiveness analyses ( CEA ) included the change in Sheehan Disability Scale ( SDS ) score ( primary CEA ) , treatment response ( MADRS score decrease > or=50 % ) and remission ( MADRS score < or=12 ) rates at week 24 . Cost outcomes were assessed from the societal perspective . Healthcare re source use and sick leave were evaluated using a health economic assessment question naire . Unit costs of healthcare services were obtained from st and ard UK sources ( pound , year 2006 values ) . RESULTS Over the total 24-week study period , escitalopram was associated with significant cost savings compared with duloxetine ( total per-patient monthly cost pound 188 vs pound 334 , respectively ) . In the primary CEA , escitalopram dominated duloxetine ( i.e. was more effective on the disability scale and less costly ) . Treatment with escitalopram result ed in significantly lower mean sick leave duration per patient over 24 weeks than duloxetine ( 30.7 days vs 62.2 days).In multivariate analyses , escitalopram as a treatment choice was associated with a 54 % reduction in sick leave duration ( p < 0.001 ) . Treatment with escitalopram also result ed in 49 % lower total costs than treatment with duloxetine ( p = 0.002 ) . Absenteeism accounted for about two-thirds of the overall cost . Early clinical improvement ( mean change in MADRS total score , response and remission ) had an independent significant impact on the sick leave duration , after controlling for key co-variates . CONCLUSIONS Escitalopram was associated with significantly lower duration of sick leave and significant savings in the total cost compared with duloxetine ; it dominated duloxetine when effectiveness was assessed on the SDS scale . Indirect costs due to sick leave accounted for the most substantial portion of the total cost and should , therefore , be an important consideration when pharmacoeconomic comparisons between treatments are made from the societal perspective . The link between decrease in absenteeism and early ( 8-week ) clinical improvement suggested in the additional analyses may explain the reduced sick leave observed with escitalopram , given its superior short-term efficacy compared with duloxetine ( demonstrated in the underlying clinical trial ) BACKGROUND Despite treatment advances , major depressive disorder ( MDD ) is still a significant cause of morbidity and mortality . Current therapies frequently fall short of providing full remission . In addition , physical symptoms are commonly seen in MDD patients , increasing overall morbidity and health care utilization . Duloxetine hydrochloride , a dual reuptake inhibitor of serotonin and norepinephrine , was evaluated for efficacy and tolerability/safety in the treatment of MDD and associated physical symptoms . METHOD In this multicenter , double-blind , parallel-group study , adult patients with DSM-IV MDD were r and omly assigned to receive placebo ( N = 122 ) or duloxetine ( 60 mg/day , N = 123 ) for 9 weeks . The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score . Painful physical symptoms were assessed using visual analog scales , and global illness and quality of life were evaluated using the Clinical Global Impressions-Severity scale , the Patient Global Impressions-Improvement scale , and the Quality of Life in Depression Scale . Safety and tolerability were determined by monitoring discontinuation rates , adverse events , vital signs , and laboratory results . RESULTS Duloxetine was significantly superior to placebo ( p < .001 ) in reducing HAM-D-17 total scores , starting at week 2 . The estimated probability of remission for duloxetine-treated patients ( 44 % ) was almost 3 times that of placebo patients ( 16 % ) . Duloxetine significantly reduced painful physical symptoms in comparison with placebo .  Discontinuation due to adverse events for duloxetine-treated patients ( 13.8 % ) compared favorably with the rates reported for SSRIs in other studies . Nausea , dry mouth , and somnolence were the most common adverse events ; no significant incidence of hypertension was seen . CONCLUSION Duloxetine , 60 mg/day , is a well-tolerated and effective treatment for MDD that reduces painful physical symptoms . These findings suggest that duloxetine may be a first-line treatment for patients with MDD and associated painful physical symptoms Abstract Background and objective : Escitalopram is the most selective serotonin reuptake inhibitor antidepressant ; in contrast , duloxetine inhibits both serotonin and norepinephrine reuptake . Double-blind comparison studies may help guide treatment decisions by revealing the relative benefits of different therapeutic approaches . This study evaluated the efficacy and safety of escitalopram versus duloxetine in the acute treatment of patients with moderate to severe major depressive disorder . Methods : A 1-week , single-blind , placebo lead-in period followed by an 8-week , r and omised , double-blind , multicentre , parallel-group comparison was conducted from 20 April 2005 to 10 March 2006 in independent psychiatric research facilities with principal investigators who were board certified in psychiatry . A total of 278 out patients of 382 patients screened with Diagnostic and Statistical Manual of Mental Disorders ( 4th edition)-diagnosed major depressive disorder ( Montgomery-Åsberg Depression Rating Scale [ MADRS ] total score ≥26 ) were r and omised to the two treatment groups . Eight patients received no medication and were excluded from the safety group . Patients were treated with either escitalopram 10–20 mg/day ( fixed at 10 mg/day for the first 4 weeks ) or duloxetine 60 mg/day . The primary efficacy variable was change from baseline at week 8 in MADRS total score using the last observation carried forward ( LOCF ) approach . Efficacy , safety and tolerability measures were prospect ively defined in the statistical analysis plan prior to study initiation unless otherwise specifically noted as conducted post hoc . Results : A significantly greater proportion of escitalopram-treated patients completed the 8-week study compared with duloxetine-treated patients ( 87 % vs 69 % , respectively ; p < 0.01 ) . Mean baseline MADRS total scores were 31.0 for the escitalopram group and 31.6 for the duloxetine group . At week 8 , escitalopram treatment result ed in significantly greater improvement compared with duloxetine on the prospect ively defined primary efficacy endpoint of mean change from baseline in MADRS total score using the LOCF approach ( least-squares mean difference [ LSMD ] −2.42 ; 95 % CI −4.73 , −0.11 ; p < 0.05 ) . There was no difference between treatment groups in the observed cases ( OC ) analysis ( LSMD −0.32 ; 95 % CI −2.71 , 2.07 ; p = 0.79 ) . Significantly fewer escitalopram-treated patients discontinued because of adverse events  compared with duloxetine ( 2 % vs 13 % , respectively ; p < 0.01 ) . Conclusion : These findings suggest that escitalopram is better tolerated and at least as effective as the serotonin-norepinephrine reuptake inhibitor duloxetine in the treatment of major depressive disorder 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
Conclusion Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine .
Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate .
In the absence of relevant data from head-to-head comparison trials , results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine
Background Data comparing duloxetine with existing antidepressant treatments is limited .
A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine , the other antidepressant in the same therapeutic class with a significant market share , has been undertaken .
In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal , indirect comparisons are the most rigorous way to go .
We conducted a systematic review of the efficacy of duloxetine , fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder ( MDD ) , and performed indirect comparisons through meta-regressions .