Reduced Suicidal Ideation in Bipolar I Disorder Mixed-Episode Patients in a Placebo-Controlled Trial of Olanzapine Combined With Lithium or Divalproex.

Objective: To identify symptoms associated with suicidality in bipolar I disorder patients, and to assess suicide risk during treatment with olanzapine in combination with lithium or divalproex.

Method: 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 divalproex 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.

J Clin Psychiatry 2006;67(8):1246-1252