title: Reduced suicidal ideation in bipolar I disorder mixed-episode patients in a placebo-controlled trial of olanzapine combined with lithium or divalproex.
abstract: OBJECTIVE
  To identify symptoms associated with suicidality in bipolar I disorder patients, and to assess suicide risk during treatment with olan-zapine in combination with lithium or divalproex.
  
  
  METHODS
  We used data from a study (conducted from September 1997 to October 2000) in which DSM-IV bipolar I manic or mixed-episode patients who were partially responsive to at least 2 weeks of lithium or dival-proex monotherapy prior to study entry were randomly assigned to augmentation therapy with olanzapine (5-20 mg/day) or placebo. Among mixed-episode patients with residual suicidality (Hamilton Rating Scale for Depression-item 3 [HAM-D-3] score of 1 or above) at randomization to cotherapy, we identified items in the Young Mania Rating Scale, Positive and Negative Syndrome Scale, and Barnes Akathisia Rating Scale that correlated with HAM-D-3 scores. We used factor analysis of correlated items to identify symptom domains associated with suicidality ratings and assessed changes in symptom factors and HAM-D-3 scores during 6 weeks of combination therapy with olanzapine versus placebo.
  
  
  RESULTS
  In 58 mixed-episode patients, mean +/- SD HAM-D-3 scores averaged 1.36 +/- 0.55 after at least 2 weeks of initial mood stabilizer monotherapy prior to study entry. Factors associated with the HAM-D-3 appeared to represent somatic discomfort, agitated depression, and psychotic features. Combination therapy with olanzapine (N = 36) versus placebo (N = 22) differentially reduced HAM-D-3 scores by 58% versus 29% (p < .05) within 1 week, and all 3 associated symptom factors within 2 weeks by averages of 31% versus 12% (p < .05).
  
  
  CONCLUSIONS
  Suicidality in adult, mixed-episode, bipolar I disorder patients was associated with somatic discomfort, agitated depression, and psychosis. Overall, these findings suggest that the addition of an atypical antipsychotic-antimanic agent in some bipolar disorder patients may help to reduce suicidal ideation.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46221, USA. houstonjp@lilly.com
authors.forename: John P
authors.initials: JP
authors.lastname: Houston
authors.forename: Jonna
authors.initials: J
authors.lastname: Ahl
authors.forename: Adam L
authors.initials: AL
authors.lastname: Meyers
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kaiser
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010919:Placebos; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012307:Risk Factors; D013405:Suicide / Q000523:psychology*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D014635:Valproic Acid; D008094:Lithium; D000077152:Olanzapine