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Olanzapine/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: a post hoc analysis.
J Clin Psychiatry. 2009 Oct; 70(10):1424-31.JC

Abstract

OBJECTIVE

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. 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.

METHOD

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. Subjects 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 > or = 2 manic/hypomanic symptoms (ie, > or = 2 Young Mania Rating Scale [YMRS] items scoring > or = 2). Response was defined as a > or = 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 > or = 15.

RESULTS

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% CI, 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. 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; 95% CI, 1.61-7.54; placebo vs olanzapine: OR = 1.30; 95% CI, 0.84-2.01).

CONCLUSION

Olanzapine/fluoxetine combination may be an effective treatment for bipolar I mixed depression. Statistically, the efficacy of OFC was not significantly different from that of olanzapine, but inspection of the 95% CI showed a trend in favor of a possible superiority of OFC. Supporting the study findings are the similar efficacy of OFC in bipolar mixed depression independent of the number of concurrent manic/hypomanic symptoms, a lower dropout rate, and a similarly low switching rate compared to olanzapine. Contrary to other current limited evidence, an antidepressant (fluoxetine) showed efficacy and did not worsen bipolar mixed depression if combined with a mood-stabilizing agent (olanzapine).

Authors+Show Affiliations

Hecker Psychiatry Research Center, Forli, Italy. FrancoBenazzi@FBenazzi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19906346

Citation

Benazzi, Franco, et al. "Olanzapine/fluoxetine Combination for the Treatment of Mixed Depression in Bipolar I Disorder: a Post Hoc Analysis." The Journal of Clinical Psychiatry, vol. 70, no. 10, 2009, pp. 1424-31.
Benazzi F, Berk M, Frye MA, et al. Olanzapine/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: a post hoc analysis. J Clin Psychiatry. 2009;70(10):1424-31.
Benazzi, F., Berk, M., Frye, M. A., Wang, W., Barraco, A., & Tohen, M. (2009). Olanzapine/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: a post hoc analysis. The Journal of Clinical Psychiatry, 70(10), 1424-31. https://doi.org/10.4088/JCP.08m04772gre
Benazzi F, et al. Olanzapine/fluoxetine Combination for the Treatment of Mixed Depression in Bipolar I Disorder: a Post Hoc Analysis. J Clin Psychiatry. 2009;70(10):1424-31. PubMed PMID: 19906346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Olanzapine/fluoxetine combination for the treatment of mixed depression in bipolar I disorder: a post hoc analysis. AU - Benazzi,Franco, AU - Berk,Michael, AU - Frye,Mark A, AU - Wang,Wei, AU - Barraco,Alessandra, AU - Tohen,Mauricio, PY - 2008/10/03/received PY - 2009/01/02/accepted PY - 2009/11/13/entrez PY - 2009/11/13/pubmed PY - 2009/12/16/medline SP - 1424 EP - 31 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 70 IS - 10 N2 - OBJECTIVE: 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. 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. METHOD: 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. Subjects 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 > or = 2 manic/hypomanic symptoms (ie, > or = 2 Young Mania Rating Scale [YMRS] items scoring > or = 2). Response was defined as a > or = 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 > or = 15. RESULTS: 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% CI, 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. 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; 95% CI, 1.61-7.54; placebo vs olanzapine: OR = 1.30; 95% CI, 0.84-2.01). CONCLUSION: Olanzapine/fluoxetine combination may be an effective treatment for bipolar I mixed depression. Statistically, the efficacy of OFC was not significantly different from that of olanzapine, but inspection of the 95% CI showed a trend in favor of a possible superiority of OFC. Supporting the study findings are the similar efficacy of OFC in bipolar mixed depression independent of the number of concurrent manic/hypomanic symptoms, a lower dropout rate, and a similarly low switching rate compared to olanzapine. Contrary to other current limited evidence, an antidepressant (fluoxetine) showed efficacy and did not worsen bipolar mixed depression if combined with a mood-stabilizing agent (olanzapine). SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/19906346/Olanzapine/fluoxetine_combination_for_the_treatment_of_mixed_depression_in_bipolar_I_disorder:_a_post_hoc_analysis_ L2 - http://www.psychiatrist.com/jcp/article/pages/2009/v70n10/v70n1011.aspx DB - PRIME DP - Unbound Medicine ER -