title: Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study.
abstract: OBJECTIVE
  Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex.
  
  
  METHODS
  This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest.
  
  
  RESULTS
  Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness.
  
  
  CONCLUSIONS
  In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.
authors.affiliation: Lilly Research Laboratories, IN 46285, USA. m.tohen@lilly.com
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.forename: Mark
authors.initials: M
authors.lastname: Frye
authors.forename: Lori
authors.initials: L
authors.lastname: Altshuler
authors.forename: John
authors.initials: J
authors.lastname: Zajecka
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Schuh
authors.forename: Richard C
authors.initials: RC
authors.lastname: Risser
authors.forename: Eileen
authors.initials: E
authors.lastname: Brown
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baker
mesh_terms: D000208:Acute Disease; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D014635:Valproic Acid; D000077152:Olanzapine