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

John P. Houston, MD, PhD; Jonna Ahl, PhD; Adam L. Meyers, MS; Christopher J. Kaiser, PhD; Mauricio Tohen, MD; Ross J. Baldessarini, MD

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

Article Abstract

Objective: To identify symptoms associated withsuicidality in bipolar I disorder patients, and to assess suiciderisk during treatment with olanzapine in combination with lithiumor divalproex.

Method: We used data from a study (conductedfrom September 1997 to October 2000) in which DSM-IV bipolar Imanic or mixed-episode patients who were partially responsive toat least 2 weeks of lithium or divalproex monotherapy prior tostudy entry were randomly assigned to augmentation therapy witholanzapine (5-20 mg/day) or placebo. Among mixed-episode patientswith residual suicidality (Hamilton Rating Scale forDepression-item 3 [HAM-D-3] score of 1 or above) at randomizationto cotherapy, we identified items in the Young Mania RatingScale, Positive and Negative Syndrome Scale, and Barnes AkathisiaRating Scale that correlated with HAM-D-3 scores. We used factoranalysis of correlated items to identify symptom domainsassociated with suicidality ratings and assessed changes insymptom factors and HAM-D-3 scores during 6 weeks of combinationtherapy with olanzapine versus placebo.

Results: In 58 mixed-episode patients, mean ± SDHAM-D-3 scores averaged 1.36 ± 0.55 after at least 2 weeks ofinitial mood stabilizer monotherapy prior to study entry. Factorsassociated with the HAM-D-3 appeared to represent somaticdiscomfort, 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 factorswithin 2 weeks by averages of 31% versus 12% (p < .05).

Conclusions: Suicidality in adult,mixed-episode, bipolar I disorder patients was associated withsomatic discomfort, agitated depression, and psychosis. Overall,these findings suggest that the addition of an atypicalantipsychotic-antimanic agent in some bipolar disorder patientsmay help to reduce suicidal ideation.