"Mixed depression (ie, co-occurrence of syndromal depression and subsyndromal mania/hypomania) is a common variant of bipolar depression. However, its treatment is much understudied," scientists writing in the Journal of Clinical Psychiatry report (see also Bipolar Disorder).

"The aim of the study was to assess the efficacy of the antipsychotic and mood-stabilizing agent olanzapine and the efficacy of the combination of an antidepressant (fluoxetine) and olanzapine (olanzapine/fluoxetine combination; OFC) for the treatment of bipolar I mixed depression. We carried out a post hoc analysis of an 8-week, double-blind trial of adult bipolar I depression treated with placebo (n = 355), olanzapine (5-20 mg/d; n = 351), or OFC (olanzapine/fluoxetine doses: 6/25, 6/50, 12/50 mg/d; n = 82). Studying mixed depression was not a previous goal of the double-blind trial. in the trial were diagnosed according to DSM-IV and were randomly assigned to treatment during the period June 2000 to December 2001. Mixed depression was defined as the co-occurrence of a major depressive episode and:2 manic/hypomanic symptoms (ie, >= 2 Young Mania Rating Scale [YMRS] items scoring 2). Response was defined as >= 50% reduction in Montgomery-Asberg Depression Rating Scale score and < 2 concurrent manic/hypomanic symptoms. Switching to mania/hypomania was defined as a YMRS score >= 15. Frequency of mixed depression was 45.1% in the OFC arm, 49.3% in the olanzapine arm, and 46.8% in the placebo arm (P=.705). The most frequent manic/hypomanic symptoms of mixed depression were irritability, reduced need for sleep, talkativeness, and racing thoughts. Response rates in patients with nonmixed depression versus patients with mixed depression were the following: in the OFC arm, 48.9% versus 43.2% (OR = 1.24; 95% CI, 0.51-2.98); in the olanzapine arm, 39.9% versus 26.6% (OR = 1.84; 95% Cl, 1.17-2.90); in the placebo arm, 27.5% versus 16.3% (OR = 1.94; 95% CI, 1.15-3.28). Response rates in the samples of patients with mixed depression were the following: OFC versus olanzapine, OR = 2.00 (95% CI, 0.96-4.19); OFC versus placebo, OR = 3.91 (95% CI, 1.80-8.49); olanzapine versus placebo, OR = 1.95 (95% CI, 1.14-3.34). It was found that no baseline manic/hypomanic symptom of mixed depression predicted treatment response. A higher number of baseline concurrent manic/hypomanic symptoms predicted a lower response rate in the olanzapine and placebo arms, but not in the OFC arm. The rates of switching were the following: in the OFC arm, 8.5%; in the olanzapine arm, 6.8%; and in the placebo arm, 7.9% (P=.808). The rates of dropouts in patients with mixed depression versus patients with nonmixed depression were not significantly different within any of the treatment arms," wrote F. Benazzi and colleagues.

The researchers concluded: "The rates of dropouts in the samples of patients with mixed depression were the following: in the OFC arm, 29.7%; in the olanzapine arm, 53.8%; and in the placebo arm, 59.6% (olanzapine vs OFC: OR = 2.66; 95% CI, 1.23-5.75; placebo vs OFC: OR=3.48;."

Benazzi and colleagues published their study in the Journal of Clinical Psychiatry (Olanzapine/Fluoxetine Combination for the Treatment of Mixed Depression in Bipolar I Disorder: A Post Hoc Analysis. Journal of Clinical Psychiatry, 2009;79(10):1424-1431).

Additional information can be obtained by contacting F. Benazzi, Via Pozzetto 17, I-48015 Cervia, RA, Italy.

The publisher of the Journal of Clinical Psychiatry can be contacted at: Physicians Postgraduate Press, PO Box 240008, Memphis, TN 38124, USA.