Differential Antidepressant Symptom Efficacy: Placebo-Controlled Comparisons of Duloxetine and SSRIs (Fluoxetine, Paroxetine, Escitalopram) Escitalopram and duloxetine in major depressive disorder: a pharmacoeconomic comparison using UK cost data. Incidence and duration of antidepressant-induced nausea: duloxetine compared with paroxetine and fluoxetine. A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study* Variation in Catechol-O-Methyltransferase Is Associated with Duloxetine Response in a Clinical Trial for Major Depressive Disorder Double-Blind Comparison of Escitalopram and Duloxetine in the Acute Treatment of Major Depressive Disorder Comparative clinical profile of mirtazapine and duloxetine in practical clinical settings in Japan: a 4-week open-label, parallel-group study of major depressive disorder Comparative study of the effects of venlafaxine and duloxetine on chemotherapy-induced peripheral neuropathy Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. Improvement of psychic and somatic symptoms in adult patients with generalized anxiety disorder: examination from a duloxetine, venlafaxine extended-release and placebo-controlled trial. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. Duloxetine treatment of dysthymia and double depression: an open-label trial. 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. Selective Serotonergic (SSRI) Versus Noradrenergic (SNRI) Reuptake Inhibitors with and without Acetylsalicylic Acid in Major Depressive Disorder. Clinical outcomes of patients with major depressive disorder treated with either duloxetine, escitalopram, fluoxetine, paroxetine, or sertraline Duloxetine in the treatment of major depressive disorder NGF serum levels variations in major depressed patients receiving duloxetine
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 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 ) OBJECTIVE This analysis assessed the incidence , severity , onset , and duration of nausea among patients with major depressive disorder ( MDD ) treated with the new antidepressant duloxetine .  METHODS Data were pooled from 8 double-blind , r and omized , placebo- and active comparator-controlled trials employing patients with MDD that were su bmi tted to the US Food and Drug Administration to support duloxetine 's new drug application for treatment of MDD . RESULTS The numbers of patients receiving each regimen were as follows : placebo , n = 777 ;  duloxetine 40 mg/d , n = 177 ; duloxetine 60 mg/d , n = 251 ; duloxetine 80 mg/d , n = 363 ; duloxetine 120 mg/d , n = 348 ; paroxetine 20 mg/d , n = 359 ; and fluoxetine 20 mg/d , n = 70 . In acute placebo-controlled trials of duloxetine 40 to 120 mg/d , treatment-emergent nausea was reported by more duloxetine-treated patients than those receiving placebo ( 19.9 % [ 227/1139 ] vs 6.9 % [ 154/777 ] , respectively ; P < 0.001 ) . Among duloxetine-treated patients , the median time to onset of nausea was 1 day , and the median duration of nausea was 7 days . The incidence of nausea was similar to placebo rates after 1 week . In paroxetine-controlled studies , the incidence of treatment-emergent nausea in patients receiving duloxetine did not differ significantly from paroxetine ( 14.4 % vs 12.0 % , respectively ) . In head-to-head studies , the incidence of treatment-emergent nausea with duloxetine did not differ significantly from that with fluoxetine ( 17.1 % vs 15.7 % , respectively ) . Most duloxetine-treated patients reported nausea to be mild ( 52.9 % ) or moderate ( 41.4 % ) . Treatment discontinuation secondary to nausea occurred in more duloxetine-treated patients than those receiving placebo ( 1.4 % [ 16/1139 ] vs 0.1 % [ 1/777 ] , respectively ; P = 0.002 ) . Following abrupt discontinuation after acute treatment , 5.9 % of duloxetine-treated patients exhibited nausea compared with 0.3 % of patients receiving placebo ( P < 0.001 ) . The incidence of treatment-emergent nausea during 6-month continuation of duloxetine treatment ( 80 mg/d , 2.1 % ; 120 mg/d , 1.3 % ) was similar to placebo ( 1.6 % ) . Following abrupt discontinuation after 8 months of treatment , nausea was reported by 1.6 % of patients receiving duloxetine 120 mg/d compared with 0 % for those receiving duloxetine 80 mg/d and 0 % for placebo . CONCLUSIONS Duloxetine induced mild to moderate nausea in a subset of patients with MDD during treatment initiation . Nausea resolved rapidly with continued treatment . The incidence of duloxetine-induced nausea resembled that produced by paroxetine and fluoxetine 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 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 The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children ( 7 - 11 years ) and adolescents ( 12 - 17 years ) with major depressive disorder ( MDD ) . METHODS Patients ( n=463 ) in this 36 week study ( 10 week acute and 26 week extension treatment ) received duloxetine 60 mg QD ( n=108 ) , duloxetine 30 mg QD ( n=116 ) , fluoxetine 20 mg QD ( n=117 , active control ) , or placebo ( n=122 ) . 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 . Total TEAEs and discontinuation for AEs were significantly ( p<0.05 ) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment . No clinical ly significant electrocardiogram ( ECG ) or laboratory abnormalities were observed , and no completed suicides or deaths occurred during the study . A total of 7 ( 6.7 % ) duloxetine 60 mg , 6 ( 5.2 % ) duloxetine 30 mg , 9 ( 8.0 % ) fluoxetine , and 11 ( 9.4 % ) placebo patients had worsening of suicidal ideation from baseline during acute treatment . Of the patients with suicidal ideation at baseline , 13/16 ( 81 % ) duloxetine 60 mg , 16/17 ( 94 % ) duloxetine 30 mg , 11/16 ( 69 % ) fluoxetine , and 13/15 ( 87 % ) placebo had improvement in suicidal ideation at end-point during acute treatment . One fluoxetine , one placebo , and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study . CONCLUSIONS 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 ( www . Clinical Trials.gov ): NCT00849693 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 BACKGROUND The study objective was to evaluate variations in genes implicated in antidepressant mechanism of action for association with response to duloxetine treatment in major depressive disorder ( MDD ) . METHODS We assessed response over 6 weeks in 250 duloxetine-treated Caucasian patients in a r and omized , double-blind study of patients with MDD . Single nucleotide polymorphisms ( SNPs ) were genotyped in 19 c and i date genes selected based on evidence for involvement in antidepressant mechanism of action . Primary analysis examined baseline to end point reduction in the 17-item Hamilton Depression Rating Scale ( HAMD17 ) total score , using a set-based test for association for each gene . Follow-up analyses examined individual SNPs within any significant gene for association with reduction in HAMD17 and 30-item Inventory of Depressive Symptomatology-Clinician Rated ( IDS-C-30 ) . RESULTS After correction for multiple comparisons , only COMT was associated with change in HAMD17 ( experiment wide p = .018 ) . Peak association was detected with rs165599 ( p = .006 ) , which accounted for approximately 3 % of variance in HAMD17 change and > 4 % of variance in IDS-C-30 change ( p = .001 ) . The least-squared mean change ( SE ) in HAMD17 score by rs165599 genotype was -10.8 ( 1.2 ) , -8.7 ( .6 ) , and -6.5 ( .7 ) for patients with GG , GA , and AA genotypes , respectively . For SNPs in serotonin 2A receptor ( HTR2A ) previously associated with citalopram response , including rs7997012 , no significant evidence of association with duloxetine response was identified . CONCLUSIONS Single nucleotide polymorphisms in COMT were associated with symptom change in duloxetine-treated patients with MDD . If replicated , the magnitude of the COMT genotype effect is of clinical relevance 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 No studies have compared mirtazapine with duloxetine in patients with major depressive disorder ( MDD ) . Fifty-six patients were nonr and omly assigned to a 4-week treatment with either 15 to 45 mg/day of mirtazapine ( n = 22 ) or 20 to 60 mg/day of duloxetine ( n = 34 ) . The primary efficacy measurements were the Hamilton Rating Scale for Depression ( HRSD ) and the Montgomery – Åsberg Depression 6-point Rating Scale ( MADRS ) scores . The second efficacy measurements were the response and remission rates of treatment . Tolerability assessment s were also performed . Fifty-six patients ( 43 male ; age , 43.6 years ) were recruited . There was no significant difference in the discontinuation rate between the mirtazapine and duloxetine treatment groups ( P = 0.867 ) . Both mirtazapine and duloxetine significantly improved the HRSD and MADRS scores from baseline ( P < 0.0001–0.0004 ) . While mirtazapine was superior to duloxetine in the reduction of HRSD scores ( P = 0.0421 ) , there was no significant change in MADRS scores in terms of between-group differences ( P = 0.171 ) . While more somnolence was observed with mirtazapine ( P = 0.0399 ) , more nausea was associated with duloxetine ( P = 0.0089 ) . No serious adverse events were observed for either antidepressant . Mirtazapine and duloxetine were safe and well-tolerated treatments for Japanese patients with MDD . Double-blind controlled studies are needed to further explore the efficacy and safety of mirtazapine and duloxetine in Japanese patients with MDD Objective One of the complications of chemotherapy is peripheral neuropathy . Various studies have shown that potent norepinephrine and serotonin reuptake inhibitors such as gabapentin , venlafaxine and duloxetine have therapeutic effects on neuropathy . The aim of this study was to compare the effects of venlafaxine vs. duloxetine on chemotherapy-induced peripheral neuropathy . Methods In this clinical trial , cancer patients who were suffering from chemotherapy-induced peripheral neuropathy comprised the study population . They were r and omly assigned to three pharmacotherapy groups including venlafaxine , duloxetine and placebo . Cranial , sensory , motor neuropathies as well as neuropathic pain were evaluated on day 1 , week 2 , and week 4 after enrollment . Results Grade of cranial , motor , sensory and neuropathic pain decreased significantly in venlafaxine and duloxetine groups . This reduction was more considerable in duloxetine group compared to venlafaxine group ( P < 0.05 ) . Conclusion Duloxetine seems to be more effective than venlafaxine in decreasing the symptoms of chemotherapy-induced peripheral neuropathy .  Duloxetine was more effective than venlafaxine in decreasing motor neuropathy and neuropathic pain grade This study examined the efficacy and tolerability of duloxetine 60–120 mg/day for the treatment of patients with generalized anxiety disorder . This was a multicenter , r and omized , double-blind , flexible-dose , placebo and active-controlled ( venlafaxine extended-release 75–225 mg/day ) trial design ed to assess duloxetine 60–120 mg/day during 10 weeks of treatment in adults with Diagnostic and statistical manual of mental disorders-IV-defined generalized anxiety disorder . The primary efficacy outcome measure was mean change from baseline to endpoint in the Hamilton Anxiety Rating Scale total score assessed using analysis of covariance . A total of 487 patients were r and omly assigned to duloxetine ( n=162 ) , venlafaxine XR ( n=164 ) , or placebo ( n=161 ) . Significantly greater improvement on the Hamilton Anxiety Rating Scale total score occurred in the duloxetine ( P=0.007 ) and venlafaxine XR ( P<0.001 ) groups compared with the placebo group . Overall discontinuation rates did not differ among the three groups , but adverse event-related discontinuation was significantly higher in the duloxetine ( 14.2 % , P<0.001 ) and venlafaxine XR ( 11.0 % , P=0.001 ) groups than in the placebo group ( 1.9 % ) . During the 2-week drug-tapering phase , discontinuation-emergent adverse events were significantly greater in the venlafaxine XR group ( 26.9 % , P=0.04 ) , but not in the duloxetine group ( 19.4 % , P=0.448 ) compared with placebo ( 15.8 % ) . Duloxetine 60–120 mg/day and venlafaxine XR 75–225 mg/day were each efficacious treatments for patients with generalized anxiety disorder 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 BACKGROUND This study examined the efficacy and tolerability of duloxetine and venlafaxine extended-release ( XR ) treatment for generalized anxiety disorder ( GAD ) , with a secondary focus on psychic and somatic symptoms within GAD . METHOD The design was a 10-week , multi-center , double-blind placebo-controlled study of duloxetine ( 20 mg or 60 - 120 mg once daily ) and venlafaxine XR ( 75 - 225 mg once daily ) treatment . Efficacy was measured using the Hamilton Anxiety Rating Scale ( HAMA ) , which includes psychic and somatic factor scores . Tolerability was measured by occurrence of treatment-emergent adverse events ( TEAEs ) and discontinuation rates . RESULTS Adult out- patients ( mean age 42.8 years ; 57.1 % women ) with DSM-IV-defined GAD were r and omly assigned to placebo ( n=170 ) , duloxetine 20 mg ( n=84 ) , duloxetine 60 - 120 mg ( n=158 ) or venlafaxine XR 75 - 225 mg ( n=169 ) treatment . Each of the three active treatment groups had significantly greater improvements on HAMA total score from baseline to endpoint compared with placebo ( p=0.01 - 0.001 ) . For the HAMA psychic factor score , both duloxetine treatment arms and venlafaxine XR demonstrated significantly greater improvement compared with placebo ( p=0.01 - 0.001 ) . For the HAMA somatic factor score , the mean improvement in the duloxetine 60 - 120 mg and venlafaxine XR groups was significantly greater than placebo ( p0.05 and p0.01 respectively ) , whose mean improvement did not differ from the duloxetine 20 mg group ( p=0.07 ) . Groups did not differ in study discontinuation rate due to adverse events . CONCLUSIONS Duloxetine and venlafaxine treatment were each efficacious for improvement of core psychic anxiety symptoms and associated somatic symptoms for adults with GAD Existing therapies for major depressive disorder ( MDD ) have either limited efficacy and /or poor tolerability . The present study examined the effects of duloxetine , a potent and balanced dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) , in patients with MDD . Adult patients ( N = 267 ) with MDD were r and omly assigned to receive duloxetine ( 60 mg/day ) or placebo in this 9-week , multi-center , double-blind , parallel-group clinical trial . Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale ( HAMD(17 ) ) , Visual Analog Scales ( VAS ) for pain , Clinical Global Impression of Severity ( CGI-S ) , Patient 's Global Impression of Improvement ( PGI-I ) , and Quality of Life in Depression Scale ( QLDS ) . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests .  Duloxetine ( 60 mg QD ) significantly reduced the HAMD(17 ) total score compared with placebo at the end of 9-week therapy . Estimated probabilities of response and remission were 65 and 43 % , respectively , for duloxetine compared with 42 and 28 % for placebo . Duloxetine also reduced overall pain , back pain , shoulder pain and time in pain while awake significantly more than placebo . Global measures of improvement , including PGI-I and QLDS , were significantly improved by duloxetine compared with placebo .  Discontinuations due to adverse events were more frequent for duloxetine-treated patients ( 12.5 % ) than for placebo-treated patients ( 4.3 % ) . Nausea , dry mouth , dizziness , and constipation were more frequent for duloxetine than placebo . There was no significant incidence of hypertension , nor any other safety issues . Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD 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 The antidepressant efficacy and short-term safety of venlafaxine and fluoxetine were compared in 68 patients hospitalized with major depression and melancholia .  Venlafaxine was superior in efficacy to fluoxetine ;  total scores for both the MADRS and the HAM-D were significantly ( p < or = 0.05 ) lower in the venlafaxine group than in the fluoxetine group at Weeks 4 and 6 . Overall tolerance was similar for the two treatments BACKGROUND Although not as common as major depressive disorder , dysthymia is not rare and is associated with substantial impairment . Antidepressants and some psychotherapies are often effective . We explored the efficacy of the antidepressant duloxetine , a serotonin and norepinephrine reuptake inhibitor . METHOD Between February 2005 and April 2006 , we recruited 24 adults with DSM-IV dysthymia or dysthymia and concurrent major depression ( " double depression " ) who had an entry score of > or = 17 on the clinician-rated Inventory for Depressive Symptomatology ( IDS-C ) . We excluded subjects with significant medical illnesses and those requiring other psychotropic agents or undergoing psychotherapy .  Subjects received duloxetine 60 mg/day for 6 weeks , increased as tolerated to 120 mg/day for the remainder of the 12-week trial for those with an inadequate treatment response . RESULTS The subjects ' mean + /- SD IDS-C scores decreased significantly from baseline ( 27.3 + /- 6.3 ) to endpoint ( 7.8 + /- 7.4 , Student t = 12.38 , df = 23 , p < or = .001 ) . The IDS-C response rate ( intent-to-treat [ ITT ] ) was 83 % ( 20/24 ) ; the remission rate ( ITT ) was 79 % ( 19/24 ) . Among study completers , these rates were 89 % ( 17/19 ) and 84 % ( 16/19 ) . Five subjects ( 21 % ) discontinued for side effects . CONCLUSION Duloxetine appears to be an effective and well-tolerated treatment for dysthymia and double depression . A double-blind , placebo-controlled study is under way . If duloxetine is found to be effective , studies powered to detect potential , clinical ly important differences between duloxetine and other antidepressants will be needed . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00185575 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 Antidepressant medication efficacy remains a major research challenge . Here , we explored four questions : whether noradrenergic antidepressants are more effective than serotonergic antidepressants ; whether the addition of 100 mg acetylsalicylic acid ( ASA ) changes antidepressant efficacy ; whether the long-term efficacy differs depending on the antidepressant and the addition of ASA ; and whether serum levels of brain-derived neurotrophic factor ( BDNF ) are clinical ly informative . SUBJECTS AND METHODS In a two-year study , forty people with major depressive disorder were r and omly assigned to groups that received an SSRI ( escitalopram ) or an SNRI ( duloxetine ) , each group received concomitant ASA ( 100 mg ) or a placebo . Sociodemographic data were recorded and patients under went regular assessment s with the Hamilton depression scale ( HDS ) and clinical global impression ( CGI ) scale . Serum levels of BDNF were measured four times per year . RESULTS There was no significant difference in efficacy between the two antidepressants or between antidepressant treatment with and without ASA . However , subgroup comparisons revealed that the duloxetine + ASA ( DASA ) subgroup showed a more rapid improvement in HDS score as early as 2 months ( t=-3.114 , p=0.01 ) , in CGI score at 5 months ( t=-2.119 , p=0.05 ) , and a better remission rate ( χ2=6.296 , p 0.012 ) than the escitalopram + placebo ( EP ) subgroup . Serum BDNF before treatment was also higher in the DASA subgroup than in the EP subgroup ( t=3.713 ; p=0.002 ) . CONCLUSION This suggest two hypotheses : either a noradrenergic agent combined with ASA is more effective in treating depression than a serotonergic agent alone , or the level of serum BDNF before treatment is a precursor marker of the response to antidepressants . Further research is needed to test these hypotheses Purpose To compare treatment outcomes in patients with major depressive disorder treated with duloxetine , escitalopram , fluoxetine , paroxetine , or sertraline for up to 6 months . Patients and methods Data were taken from a 6-month prospect i ve , observational study that included 1,549 major depressive disorder patients without sexual dysfunction in 12 countries . We report the overall results and those from Asian countries .  Depression severity was measured using the Clinical Global Impression and the 16-item Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR16 ) . Clinical and functional remissions were defined as having a QIDS-SR16 < 6 , and as having a rating of <3 on all three Sheehan Disability Scale items and no reduced productivity , respectively . Mixed effects modeling with repeated measures analysis and generalized estimating equation models were used . Propensity scores were included in the models . Results The mixed effects modeling with repeated measures regression models showed that the Clinical Global Impression rating during follow-up was significantly lower in those patients treated with duloxetine compared with escitalopram ( 0.40 , 95 % CI 0.25 to 0.56 ) ; fluoxetine ( 0.22 , 95 % CI 0.05 to 0.38 ) ; paroxetine ( 0.38 , 95 % CI 0.23 to 0.54 ) ; and sertraline ( 0.32 , 95 % CI 0.16 to 0.49 ) . The QIDS-SR16 of duloxetine-treated patients was significantly lower than those treated with escitalopram ( 1.58 , 95 % CI 1.03 to 2.12 ) ; fluoxetine ( 1.48 , 95 % CI 0.90 to 2.06 ) ; paroxetine ( 1.53 , 95 % CI 1.00 to 2.07 ) ; and sertraline ( 1.19 , 95 % CI 0.61 to 1.78 ) . The probability of clinical remission of the patients treated with escitalopram , fluoxetine , paroxetine , and sertraline was lower than those treated with duloxetine ( OR 0.46 , 95 % CI 0.33 to 0.64 ; OR 0.42 , 95 % CI 0.29 to 0.61 ; OR 0.40 , 95 % CI 0.29 to 0.56 ; OR 0.50 , 95 % CI 0.35 to 0.71 ; respectively ) . The regression analysis of functional remission also showed more favorable results for duloxetine , with OR ranging from 0.43 , 95 % CI 0.31 to 0.60 for paroxetine to 0.49 , 95 % CI 0.35 to 0.70 for sertraline . The results for the Asian countries were generally consistent . Conclusion Duloxetine-treated patients had better 6-month outcomes in terms of depression severity and clinical and functional remission , compared with selective serotonin reuptake inhibitor-treated patients Since depression impacts all body systems , antidepressant treatments should relieve both the emotional and physical symptoms of depression . Duloxetine demonstrated antidepressant efficacy at a dose of 60 mg qd in two placebo-controlled , r and omized , double-blind studies and significantly improved remission rates compared with placebo . Duloxetine-treated patients had significant reduction in severity of the symptoms of depression as assessed by the HAM-D17 , anxious symptoms as measured by the HAM-A and quality of life measures compared to placebo . Duloxetine also improved somatic symptoms , particularly painful symptoms which may have contributed to significantly improved remission rates compared to placebo . Approximately 10 % of the 1139 patients with major depressive disorder in placebo-controlled trials discontinued treatment due to an adverse event , compared to 4 % of the 777 patients receiving placebo .  In addition to nausea ( 1.4 % incidence ) , which was the most common reason for discontinuation , dizziness , somnolence , and fatigue were the most common AEs reported as reasons for discontinuation and all were considered drug-related . Duloxetine treatment lacks effects on ECG , increases heart rate , and has little effect on blood pressure or weight BACKGROUND S Nerve growth factor ( NGF ) is involved in the modulation of the neuro-endocrine-immune ( NEI ) system , whereas alterations in neuroplasticity and NEI homeostasis seem to play a role in the pathophysiology of major depressive disorder ( MDD ) . Objective of the study was to investigate NGF levels variations in MDD patients during  antidepressant treatment with duloxetine , a relatively newer SNRI . METHODS 30 MDD patients and 32 healthy controls were assessed using Hamilton depression scale ( HAM-D ) and monitored for  NGF serum levels at baseline , week 6 and week 12 of duloxetine treatment ( 60 mg/day ) and at baseline , respectively . RESULTS According to early clinical response to duloxetine ( defined at week 6 by reduction > 50 % of baseline HAM-D score ) , MDD patients were distinguished in early responders ( ER ) and early non-responders ( ENR ) , who overall reached clinical response at week 12 . Laboratory analysis showed overall significant lower baseline NGF levels among depressed patients compared to healthy controls , not significantly in ER and significantly in ENR . During duloxetine treatment NGF levels further decreased in association with clinical response , reaching significantly lower values in ER at W6 compared to controls , and in ENR at W12 compared to baseline . CONCLUSIONS A decrease in NGF levels during duloxetine treatment in association to clinical response could be indicative of a relative restoring of NEI stress-adaptation system , since stressors , inducing neuronal instability due to neurotrophins activity changes , permits circuitry remodeling as background in the selection of alternative adaptive behaviors . However , the lower baseline NGF levels found in MDD patients that further decrease during the treatment could represent a lower neurotrophin set point , possibly reflecting a functional impairment in stress-adaptive neuroplasticity in depressive disorders
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 .