title: Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hypericum perforatum versus fluoxetine.
abstract: BACKGROUND
  Our objective was to assess for the relationship between timing of clinical improvement and resolution of depressive symptoms during the treatment of major depressive disorder (MDD). Thirty-nine MDD outpatients who responded following a 12-week, double-blind study comparing Hypericum perforatum, fluoxetine or placebo were included in the analysis.
  
  
  METHODS
  Onset of clinical improvement was defined as a 25% decrease in 17-item Hamilton Depression Scale (HDRS-17) scores that was not followed by a subsequent worsening of symptoms. Controlling for baseline symptom severity, we then assessed for the relationship between timing of clinical improvement and depressive symptom severity at endpoint.
  
  
  RESULTS
  Among responders, earlier clinical improvement predicted lower HDRS-17 scores at week 12 (p = 0013). This was also true of responders who received active treatment (n = 29, p = 0.0113) but not placebo responders (n = 10; p > 0.05). Finally, patients with an early onset of clinical improvement (occurring during the first 2 weeks) had lower week 12 HDRS-17 scores than patients with a late onset of clinical improvement (p = 0.0404).
  
  
  CONCLUSIONS
  In the present work, earlier as well as early clinical improvement during treatment is predictive of greater symptom resolution at endpoint among responders. This was replicated among patients who received active treatment (either hypericum or fluoxetine) but not placebo.
authors.affiliation: Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 02114, USA. gpapakostas@partners.org
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: Christine M
authors.initials: CM
authors.lastname: Crawford
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Scalia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D020902:Hypericum; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy / Q000379:methods*; D028321:Plant Preparations / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005473:Fluoxetine; D028321:Plant Preparations; D017367:Selective Serotonin Reuptake Inhibitors