title: Safety and efficacy of olanzapine monotherapy and olanzapine with a mood stabilizer in 18-week treatment of manic/mixed episodes for Japanese patients with bipolar I disorder.
abstract: OBJECTIVE
  To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer.
  
  
  METHODS
  In this open-label, multicenter extension study, patients who completed the acute study received olanzapine (5-20 mg/day) as monotherapy, and patients who discontinued the acute study due to lack of efficacy with greater Young Mania Rating Scale (YMRS) total score than the acute study baseline, received olanzapine in combination with one of three mood stabilizers: lithium, carbamazepine, or valproate. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, weight, and extrapyramidal symptoms (EPSs). Efficacy measures included YMRS total score, and response and remission rates of manic symptoms.
  
  
  METHODS
  There were no deaths or serious adverse events considered potentially related to olanzapine in the monotherapy group (N = 100) or the combination-therapy group (N = 39). TEAEs occurred in 59.0% and 79.5% of patients in the monotherapy and combination-therapy groups, respectively, and their severities were mostly mild or moderate. Regarding the efficacy measures, in the monotherapy group, mean YMRS change from extension study baseline to endpoint was -3.0, and the response and remission rates at endpoint were 97.0% and 93.0%, respectively. In the combination-therapy group, mean YMRS change from extension-study baseline was -19.8; response and remission rates increased from the extension-study baseline (both 0.0%) to 64.1% and 61.5% respectively by endpoint.
  
  
  CONCLUSIONS
  Olanzapine was generally well tolerated during the 18-week extension period in Japanese patients with bipolar mania. Results of both groups were also generally consistent with US and European studies. Monitoring of metabolic parameters is recommended.
authors.affiliation: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan. katagiri_hideaki@lilly.com
authors.forename: Hideaki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takita
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Kanba
authors.forename: Michihiro
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D002220:Carbamazepine / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007564:Japan; D008094:Lithium / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D002220:Carbamazepine; D014635:Valproic Acid; D011388:Prolactin; D008094:Lithium; D000077152:Olanzapine