title: Efficacy comparison of duloxetine and SSRIs at doses approved in Japan.
abstract: BACKGROUND
  Approved doses of antidepressants in Japan are usually lower than those in the USA and European Union, but to date meta-analyses comparing antidepressants have all used the higher doses approved in the USA and European Union and often have used indirect comparisons. The purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors (SSRIs) at the doses approved in Japan.
  
  
  METHODS
  Pooled data were analyzed from four randomized, double-blind, placebo-controlled studies that compared duloxetine at the dose range approved in Japan (40-60 mg/day) with other SSRIs (paroxetine 20 mg/day or escitalopram 10 mg/day) and placebo in patients with major depressive disorder. In total, 1,694 patients were included in the analysis (duloxetine, n=688; selective serotonin reuptake inhibitors, n=690; placebo, n=316). The primary outcome measure was the mean change from baseline at week 8 in 17-item Hamilton Rating Scale for Depression (HAMD17) total and subscale scores.
  
  
  RESULTS
  Duloxetine and both selective serotonin reuptake inhibitors were superior to placebo in HAMD17 total score at week 8 in both the all-randomized group and the more severe subgroup (HAMD17 total scores ≥19). Duloxetine was superior to SSRIs in improving the HAMD17 Retardation subscale score (least squares mean difference [95% confidence interval]): all-randomized group, -0.33 [-0.60, -0.07], P=0.015; severe subgroup, -0.45 [-0.83, -0.07], P=0.020).
  
  
  CONCLUSIONS
  Within the dose range approved in Japan for patients with major depressive disorder, duloxetine and selective serotonin reuptake inhibitors demonstrated comparable overall efficacy, with a possible advantage for duloxetine in improving loss of energy and interest. To the best of our knowledge, this analysis is unique not only in evaluating dosages specific to Japan, but also in using individual patient data and the same endpoint across studies to allow for strictly direct head-to-head data comparisons as opposed to pooling direct and indirect comparisons.
authors.affiliation: Medical Science, Eli Lilly Japan K.K, Kobe, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.affiliation: Global Statistical Sciences, Eli Lilly and Company, Bad Homburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schacht
authors.affiliation: Clinical Research Center, Ohyachi Hospital, Sapporo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA ; The University of Texas Health Science Center, Houston, TX, USA.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
authors.affiliation: Medical Affairs, Shionogi & Co Ltd, Osaka, Japan.
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Escobar
keywords: Japan; approved dosage; duloxetine; major depressive disorder; meta-analysis; selective serotonin reuptake inhibitors