title: Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression.
abstract: OBJECTIVE
  Current clinical knowledge holds that antidepressants have a delayed onset of efficacy. However, the delayed onset hypothesis has been questioned recently by survival analytical approaches. We aimed to test whether early improvement under antidepressant treatment is a clinically useful predictor of later stable response and remission.
  
  
  METHODS
  We analyzed data from a randomized double-blind controlled trial with mirtazapine and paroxetine in patients with major depression (DSM-IV). Improvement was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score reduction of > or = 20%. Stable response was defined as > or = 50% HAM-D-17 score reduction at week 4 and week 6, and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.
  
  
  RESULTS
  Improvement occurred in a majority of the analyzed patients within 2 weeks (mirtazapine: 72.7% of 109 patients; paroxetine: 64.9% of 103 patients). Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs. NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine. After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine, almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course.
  
  
  CONCLUSIONS
  Our results strongly suggest that early improvement predicts later stable response with high sensitivity. These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment.
authors.affiliation: Department of Psychiatry, University of Mainz, Mainz, Germany. szegedi@mail.psychiatrie.klinik.uni-mainz.de
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Müller
authors.forename: Ion
authors.initials: I
authors.lastname: Anghelescu
authors.forename: Christoph
authors.initials: C
authors.lastname: Klawe
authors.forename: Ralf
authors.initials: R
authors.lastname: Kohnen
authors.forename: Otto
authors.initials: O
authors.lastname: Benkert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D008875:Middle Aged; D000078785:Mirtazapine; D017374:Paroxetine / Q000627:therapeutic use*; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors