title: Baseline patient characteristics associated with placebo remission and their impact on remission with duloxetine and selected SSRI antidepressants.
abstract: OBJECTIVE
  We examined whether identification of patients with placebo-remitter characteristics and placebo-nonremitter characteristics enhances the ability to identify drug-placebo treatment differences and, perhaps, differences between agents in major depressive disorder (MDD). We hypothesized: 1) that drug-placebo differences in remission rates would be greater for both duloxetine and selective serotonin reuptake inhibitors (SSRIs) among placebo nonremitters than placebo remitters and: 2) that the difference between active treatments would also be greater in placebo nonremitters than placebo remitters.
  
  
  METHODS
  Data were obtained from seven randomized, parallel, double-blind MDD studies which compared the effects of duloxetine (N = 795), placebo (N = 510), and SSRIs (N = 551). The 17-item Hamilton depression rating scale (HAMD) was used to assess depression severity. The classification of participants as having placebo-remitter or placebo-nonremitter characteristics was based on age, duration of current MDD episode, HAMD anxiety score, and HAMD core score. Odds ratios (ORs) for remission comparing active treatment and placebo were obtained from logistic regression models. Tests of homogeneity were used for between-group comparisons.
  
  
  RESULTS
  For placebo nonremitters, both duloxetine (OR = 3.52 [95% CI: 2.21, 5.62; P < 0.0001]) and SSRIs (OR = 2.38 [95% CI: 1.45, 3.89; P = 0.0006]) showed significantly higher remission rates compared to placebo. Drug-placebo differences in remission were significantly greater for placebo nonremitters than for placebo remitters for both duloxetine (P = 0.02) and SSRIs (P = 0.049). For placebo remitters, remission with duloxetine (OR = 1.83 [95% CI: 1.35, 2.47; P = 0.0001]), but not the SSRIs selected for this study (OR = 1.31 [95% CI: 0.93, 1.84; P = 0.12]), was significantly greater than placebo. Contrary to expectation, the advantage of duloxetine over the SSRIs was not greater in placebo nonremitters. However, the fact that our analysis required patient-level data limited the number of agents studied, compromising generalization.
  
  
  CONCLUSIONS
  Our study suggests that drug-placebo differences in remission rates will be greater in subjects with placebo-nonremitter than with placebo-remitter characteristics.
authors.affiliation: Department of Psychiatry, University of California San Francisco, 401 Parnassus Ave, San Francisco, CA 94143, USA. craign@lppi.ucsf.edu
authors.forename: J Craig
authors.initials: JC
authors.lastname: Nelson
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Katarina
authors.initials: K
authors.lastname: Kelin
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Walter
authors.initials: W
authors.lastname: Deberdt
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D003865:Major Depressive Disorder / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D006801:Humans; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000068736:Duloxetine Hydrochloride; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes