title: Is it worth assessing progress as early as week 2 to adapt antidepressive treatment strategy? Results from a study on agomelatine and a global meta-analysis.
abstract: BACKGROUND
  A delay of 4-8weeks before modifying the prescribed antidepressant treatment is usually proposed when incomplete treatment response is observed. A number of studies nevertheless proposed that the lack of early improvement (usually 20% decrease of severity at week 2) is predictive of the absence of subsequent treatment response, potentially saving weeks of inadequate treatment, but with no information for non-interventional studies devoted to outpatients.
  
  
  METHODS
  Two thousand nine hundred and thirty-eight outpatients with major depressive disorder were included in a multicentre, non-interventional study, assessing at inclusion, week 2 and week 6, mood (QIDS-C, CGI, PGI and VAS) sleep (LSEQ) and functionality (SDS). All metrics at week 2 were tested for their capacity to predict response (and then remission) at week 6, all patients being treated by agomelatine. A meta-analysis of all studies (n=12) assessing the predictive role of improvement at week 2 was also performed, assessing specific effect size of published studies and the weight of the different parameters they used.
  
  
  RESULTS
  The QIDS-C and the CGI-I were the only instruments with an area under the curve over 0.7, with different cut-offs for treatment response and remission. A decrease of more than five points at the QIDS-C had the highest positive predictive value for treatment response, and a CGI-I over three had the highest negative predictive value, which would favour relying on the clinicians for warning (too high CGI-I), and on instruments for confidence (favourable decrease of the QIDS-C). The meta-analysis of all studies also detected a large effect size of early improvement, stressing how rating week 2 severity could be beneficial in clinical practice.
  
  
  CONCLUSIONS
  Previous reports stressing the interest of an assessment at week 2 were reinforced by the present results, which also defined more accurately what could be the most appropriate cut-offs, and how combining these early results could be more effective.
authors: Centre Hospitalier Sainte-Anne (CMME), 100, rue de la Santé, 75014 Paris, France. p.gorwood@ch-sainte-anne.fr
authors: P
authors: P
authors: Gorwood
authors: F
authors: F
authors: Bayle
authors: G
authors: G
authors: Vaiva
authors: P
authors: P
authors: Courtet
authors: E
authors: E
authors: Corruble
authors: P-M
authors: PM
authors: Llorca
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; C084711:agomelatine; D009281:Naphthalenes
keywords: Early response; Major depressive disorder; Marker; Outcome; Treatment response