title: Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms.
abstract: BACKGROUND
  Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.
  
  
  METHODS
  We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D).
  
  
  RESULTS
  The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates.
  
  
  CONCLUSIONS
  Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK. rudolf.uher@kcl.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Uher
authors.forename: R H
authors.initials: RH
authors.lastname: Perlis
authors.forename: N
authors.initials: N
authors.lastname: Henigsberg
authors.forename: A
authors.initials: A
authors.lastname: Zobel
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.forename: J
authors.initials: J
authors.lastname: Hauser
authors.forename: M Z
authors.initials: MZ
authors.lastname: Dernovsek
authors.forename: D
authors.initials: D
authors.lastname: Souery
authors.forename: M
authors.initials: M
authors.lastname: Bajs
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: K J
authors.initials: KJ
authors.lastname: Aitchison
authors.forename: A
authors.initials: A
authors.lastname: Farmer
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology*; D000328:Adult; D000339:Affect; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use*; D003071:Cognition; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D005060:Europe; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008297:Male; D009661:Nortriptyline / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D009661:Nortriptyline