title: Trajectories of depression symptom improvement and associated predictor analysis: An analysis of duloxetine in double-blind placebo-controlled trials.
abstract: BACKGROUND
  In the treatment of major depressive disorder (MDD), it is not fully understood how individual symptoms improve over time (trajectory) in remitters. This study compared symptom improvement trajectories, as measured with the 17-item Hamilton Depression Rating Scale (HAM-D17), in remitters and nonremitters.
  
  
  METHODS
  This analysis is based on 10 placebo-controlled, randomized, double-blind trials of duloxetine (40-60mg/day) for treatment of MDD from baseline up to week 8. Remission was defined as a HAM-D17 total score ≤7 at week 8 (last observation carried forward). Trajectories of HAM-D17 items were assessed by mixed model repeated measures analysis for treatment and remitter-nonremitter comparisons. Grouping of the trajectories was performed by factor analysis. Predictor analysis using HAM-D17 items was conducted by logistic regression.
  
  
  RESULTS
  There were 1555 patients in the duloxetine group (489 [31.4%] remitters) and 1206 patients in the placebo group (290 [24.0%] remitters; P<.0001). For most items, the difference in trajectories between remitters and nonremitters appeared at early time points and increased over time. Treatment response trajectories were very similar for duloxetine and placebo remitters, while duloxetine nonremitters improved more than placebo nonremitters. For duloxetine remitters, we found 3 trajectory groups of HAM-D17 items. The predictor analysis showed that improvement in 6 individual items at week 1 or 2 was significantly associated with remission at week 8.
  
  
  CONCLUSIONS
  Generalizability of these results may be limited by the relatively short observation period used to define remission.
  
  
  CONCLUSIONS
  Early monitoring of some symptoms of depression may prove useful in guiding treatment decisions.
authors.affiliation: Eli Lilly Japan K.K., Neuroscience and Pain Products, Bio-Medicines, Medicines Development Unit Japan, Kobe, Hyogo, Japan. Electronic address: tokuoka_hirofumi@lilly.com.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tokuoka
authors.affiliation: Department of Psychiatry, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Eli Lilly Japan K.K., Statistical Science, Medicines Development Unit Japan, Kobe, Hyogo, Japan.
authors.forename: Akichika
authors.initials: A
authors.lastname: Ozeki
authors.affiliation: Eli Lilly Japan K.K., Neuroscience and Pain Products, Bio-Medicines, Medicines Development Unit Japan, Kobe, Hyogo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuga
authors.affiliation: Eli Lilly Japan K.K., Scientific Communications, Medicines Development Unit Japan, Kobe, Hyogo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Yoshikawa
authors.affiliation: Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Osaka, Japan.
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Eli Lilly and Company, Neuroscience, Indianapolis, IN, USA.
authors.forename: Madelaine M
authors.initials: MM
authors.lastname: Wohlreich
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride
keywords: Depression; Duloxetine; Placebo; Predictor; Remission; Trajectory