title: Severity of depression and response to antidepressants: GENPOD randomised controlled trial.
abstract: BACKGROUND
  Antidepressant prescribing is widespread. Nonetheless, response to antidepressants is variable. If it was possible to predict response to medication and thus tailor treatment accordingly, this would not only improve patient outcomes but may also have economic benefits.
  
  
  OBJECTIVE
  To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors (NARIs) than selective serotonin reuptake inhibitors (SSRIs) compared with individuals with less severe depression.
  
  
  METHODS
  Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory (BDI) were randomised to either an SSRI (citalopram 20 mg daily) or a NARI (reboxetine 4 mg twice daily). Randomisation was by means of a remote automated telephone system. The main outcome was depressive symptoms measured by the BDI total score 6 weeks after randomisation. (
  
  
  BACKGROUND
  ISRCTN31345163.)
  
  
  RESULTS
  In total, 601 participants were randomised (citalopram: n = 298, reboxetine: n = 303). Ninety-one per cent were followed up at 6 weeks (citalopram: n = 274, reboxetine: n = 272). There was little evidence to support an interaction between treatment and severity of depression (interaction term: 0.02, 95% CI -0.59 to 0.62, P = 0.96). Adjustment for potential confounders (age, gender, employment status, history of depression, number of life events and social support) did not affect the findings (interaction term: 0.06, 95% CI -0.54 to 0.66, P = 0.85).
  
  
  CONCLUSIONS
  Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care.
authors.affiliation: Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Clifton, Bristol BS8 2BN, UK. nicola.wiles@bristol.ac.uk
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Wiles
authors.forename: Jean
authors.initials: J
authors.lastname: Mulligan
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Peters
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: Victoria
authors.initials: V
authors.lastname: Mason
authors.forename: David
authors.initials: D
authors.lastname: Nutt
authors.forename: Deborah
authors.initials: D
authors.lastname: Sharp
authors.forename: Debbie
authors.initials: D
authors.lastname: Tallon
authors.forename: Laura
authors.initials: L
authors.lastname: Thomas
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D038801:International Classification of Diseases; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D011320:Primary Health Care; D011569:Psychiatric Status Rating Scales; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D015283:Citalopram; D009025:Morpholines; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors