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Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study.
Curr Med Res Opin. 2007 Feb; 23(2):401-16.CM

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 treatment. 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 randomized, double-blind, placebo- and active comparator-controlled study, in which patients (> or = 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 (HAMD(17)) 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 < or = 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 designs 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.

Authors+Show Affiliations

Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17288694

Citation

Nierenberg, Andrew A., et al. "Duloxetine Versus Escitalopram and Placebo in the Treatment of Patients With Major Depressive Disorder: Onset of Antidepressant Action, a Non-inferiority Study." Current Medical Research and Opinion, vol. 23, no. 2, 2007, pp. 401-16.
Nierenberg AA, Greist JH, Mallinckrodt CH, et al. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Curr Med Res Opin. 2007;23(2):401-16.
Nierenberg, A. A., Greist, J. H., Mallinckrodt, C. H., Prakash, A., Sambunaris, A., Tollefson, G. D., & Wohlreich, M. M. (2007). Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Current Medical Research and Opinion, 23(2), 401-16.
Nierenberg AA, et al. Duloxetine Versus Escitalopram and Placebo in the Treatment of Patients With Major Depressive Disorder: Onset of Antidepressant Action, a Non-inferiority Study. Curr Med Res Opin. 2007;23(2):401-16. PubMed PMID: 17288694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. AU - Nierenberg,Andrew A, AU - Greist,John H, AU - Mallinckrodt,Craig H, AU - Prakash,Apurva, AU - Sambunaris,Angelo, AU - Tollefson,Gary D, AU - Wohlreich,Madelaine M, PY - 2007/2/10/pubmed PY - 2007/3/16/medline PY - 2007/2/10/entrez SP - 401 EP - 16 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 23 IS - 2 N2 - OBJECTIVE: The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment. 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 randomized, double-blind, placebo- and active comparator-controlled study, in which patients (> or = 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 (HAMD(17)) 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 < or = 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 designs 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. SN - 1473-4877 UR - https://www.unboundmedicine.com/medline/citation/17288694/Duloxetine_versus_escitalopram_and_placebo_in_the_treatment_of_patients_with_major_depressive_disorder:_onset_of_antidepressant_action_a_non_inferiority_study_ L2 - http://www.tandfonline.com/doi/full/10.1185/030079906X167453 DB - PRIME DP - Unbound Medicine ER -