title: The impact of response to previous mood stabilizer therapy on response to olanzapine versus placebo for acute mania.
abstract: OBJECTIVE
  A clinically important question for any new treatment for bipolar disorder is whether its efficacy extends to patients who have both responded and failed to respond to other mood stabilizers. In this secondary analysis of a placebo-controlled trial demonstrating olanzapine's efficacy for acute mania, we explore whether its usefulness extends to those patients with a history of poor response to other mood stabilizers.
  
  
  METHODS
  This 4-week, double-blind, placebo-controlled trial studied olanzapine monotherapy 5-20 mg/day for hospitalized patients in acute manic or mixed bipolar episodes. The primary outcome variable was beginning to endpoint change in the Young-Mania Rating Scale (Y-MRS) total score. We investigated whether prospectively identified history of recent failure to respond to other mood stabilizers predicted response to olanzapine.
  
  
  RESULTS
  As previously reported, olanzapine-treated patients experienced significantly greater improvement in Y-MRS total score and higher remission rates relative to placebo-treated patients. The current analysis compared these outcome parameters in patients with known poor prior response to lithium and/or valproate with all other patients and found no significant group by treatment interactions, i.e., treatment effects were not significantly diminished in non-responders to older mood stabilizing agents.
  
  
  CONCLUSIONS
  Olanzapine has been shown to be superior to placebo for the treatment of mania. This secondary analysis suggests that olanzapine monotherapy is similarly effective for patients whether or not they previously have failed to respond to another mood stabilizer for mania. A study limitation is that response to lithium or valproate was determined retrospectively.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. baker_robert_w@lilly.com
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baker
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Goldberg
authors.forename: Maurico
authors.initials: M
authors.lastname: Tohen
authors.forename: Denái R
authors.initials: DR
authors.lastname: Milton
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Stauffer
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Schuh
mesh_terms: D000328:Adult; D001569:Benzodiazepines; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D001569:Benzodiazepines; D000077152:Olanzapine; D010890:Pirenzepine; D017367:Selective Serotonin Reuptake Inhibitors