title: Targeting remission by 8 weeks: when should supplementation be considered in patients with major depression treated with a specific serotonin reuptake inhibitor?
abstract: BACKGROUND
  Timely administration/supplementation of a specific serotonin reuptake inhibitor with a second therapeutic agent could improve treatment outcome in patients with major depressive disorder (MDD). The purpose of this study was to identify the optimal time at which to implement supplementation so as to maximize the likelihood of remission by 8 weeks and minimize overtreatment.
  
  
  METHODS
  Data from patients with MDD treated with sertraline (n = 108) or citalopram (n = 107) in a randomized controlled trial were analyzed by multivariate logistic regression. The 21-item Hamilton Depression Scale scores at weeks 1, 2, 3, 4, and 6; sex; age; and baseline Hamilton Anxiety Scale score were used as predictors of remission by 8 weeks sustained for a further 4 weeks.
  
  
  RESULTS
  Regression models for weeks 2, 3, 4, and 6 were significant (area under the curve values, 0.73-0.91). The models for weeks 3 to 6 yielded κ coefficients greater than 0.40 with the outcome variable. A Hamilton Depression Scale reduction score of 50% at week 4 as a criterion for supplementation would have resulted in overtreatment of 4% and 0% of patients in the sertraline and citalopram groups, respectively, and none if applied at week 6. The rates at which patients who should have received supplementation (destined to be nonremitters at 8 weeks) would have been missed would be 49%/54% for sertraline/citalopram at week 4 and 43%/50% at week 6.
  
  
  CONCLUSIONS
  The study limitations are as follows: secondary analysis of data, relatively low sertraline dose, and relatively small sample sizes.
  
  
  CONCLUSIONS
  It may be possible to identify patients treated with specific serotonin reuptake inhibitors who will not achieve sustained remission by 8 weeks. If supplementation were implemented accordingly, the number of overtreated patients would be small. However, a substantial number of patients who should be supplemented would be missed, indicating a need for greater sensitivity of the prediction model. Further studies are needed.
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah–Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel.
authors.forename: Rena
authors.initials: R
authors.lastname: Cooper-Kazaz
authors.forename: Amihai
authors.initials: A
authors.lastname: Rigbi
authors.forename: Bernard
authors.initials: B
authors.lastname: Lerer
mesh_terms: D000328:Adult; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011569:Psychiatric Status Rating Scales; D012074:Remission Induction / Q000379:methods; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline