title: Early improvement as a predictor of acute treatment outcome in manic or mixed episodes in bipolar-1 disorder: a pooled, post hoc analysis from the asenapine development program.
abstract: OBJECTIVE
  To assess whether early symptom improvement predicts later treatment outcome in acute manic/mixed episodes of bipolar I disorder using Young Mania Rating Scale (YMRS) or Clinical Global Impression scale, bipolar disorders (CGI-BP) assessments.
  
  
  METHODS
  Data were pooled from two 3-week randomized controlled studies with asenapine (ASE; n=372), olanzapine (OLA; n=391), or placebo (PL; n=197). Early improvement was defined as reduction of YMRS total scores (≥15%, ≥20%, ≥25%) or CGI-BP severity scores (≥1 point change) at days 2, 4, and 7. Treatment outcome at week 3 was defined as response (YMRS: ≥50% score reduction; CGI-BP severity: "minimally ill" or better) or remission (YMRS total score ≤12; CGI-BP severity: "not at all ill"). Odds ratios (ORs) and predictive performance statistics were calculated.
  
  
  RESULTS
  Early improvement occurred in a substantial percentage of patients and was associated with significantly increased ORs for response or remission. For ASE, results were significant as early as day 2 on all measures of YMRS and CGI-severity of mania assessment. For all treatments sensitivity and negative predictive values increased from days 2 to 7 for all YMRS and CGI-BP measures, while specificity values decreased.
  
  
  CONCLUSIONS
  In acute manic/mixed episodes, early improvement within 1 week of treatment was associated with significantly increased ORs of endpoint response or remission. While only a subset of early improvers reach the endpoint treatment goals, absence of improvement within week 1 of treatment initiation strongly predicts the unlikely success of subsequent treatment. Further, CGI-based predictors had predictive properties similar to those based on the YMRS scale.
authors.affiliation: Merck, Rahway, NJ, USA. armin.szegedi@merck.com
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D003986:Dibenzocycloheptenes; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine; D000077152:Olanzapine
keywords: Antipsychotics; Bipolar mania; CGI–BP; Early improvement; YMRS