title: Assessing the 'true' effect of active antidepressant therapy v. placebo in major depressive disorder: use of a mixture model.
abstract: BACKGROUND
  There is controversy about the implications of relatively small average drug-placebo differences observed in randomised controlled trials of antidepressant medications.
  
  
  OBJECTIVE
  To investigate whether efficacy is better understood as a large effect in a subgroup of patients.
  
  
  METHODS
  The mixture model was used to identify patient subgroups (patients benefiting or not benefiting from treatment) to directly model the skewness of Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 8.
  
  
  RESULTS
  The MADRS scores improved by 15.9 points (95% CI 15.2-16.6) among patients who benefited from treatment. The proportion of patients who benefited from escitalopram and not from placebo treatment was 19.5%, corresponding to a number needed to treat of 5.
  
  
  CONCLUSIONS
  This model gave a considerably better fit to the data than the analysis of covariance model in which all patients were assumed to benefit from treatment. The small average antidepressant-placebo difference obscures a much larger effect in a clinically meaningful subgroup of patients.
authors: University of Pennsylvania School of Medicine, and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. USA. thase@mail.med.upenn.edu
authors: Michael E
authors: ME
authors: Thase
authors: Klaus G
authors: KG
authors: Larsen
authors: Sidney H
authors: SH
authors: Kennedy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors