奥氮平/氟西汀联合用药、奥氮平及氟西汀治疗难治性重度抑郁症的随机双盲对照研究

A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder.

作者信息

Thase Michael E, Corya Sara A, Osuntokun Olawale, Case Michael, Henley David B, Sanger Todd M, Watson Susan B, Dubé Sanjay

机构信息

Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

J Clin Psychiatry. 2007 Feb;68(2):224-36. doi: 10.4088/jcp.v68n0207.

DOI:10.4088/jcp.v68n0207

PMID:17335320

Abstract

OBJECTIVE

Two parallel, 8-week double-blind studies compared olanzapine/fluoxetine combination, olanzapine, and fluoxetine in outpatients with treatment-resistant depression (TRD).

METHOD

Treatment-resistant depression was defined as a documented history of current-episode antidepressant failure plus a prospective failure on fluoxetine. Following an 8-week fluoxetine lead-in, 605 nonresponders with DSM-IV major depressive disorder were randomly assigned to olanzapine/fluoxetine combination, olanzapine, or fluoxetine. The primary outcome measure was baseline-to-endpoint mean change on the Montgomery-Asberg Depression Rating Scale (MADRS). The study was conducted from April 2002 to May 2005.

RESULTS

After 8 weeks of double-blind treatment, Study 1 revealed no statistically significant therapy differences in MADRS mean change (olanzapine/fluoxetine combination: -11.0, fluoxetine: -9.4, olanzapine: -10.5). In Study 2, olanzapine/fluoxetine combination demonstrated significantly greater MADRS improvement (-14.5) than fluoxetine (-8.6, p < .001) and olanzapine (-7.0, p < .001). Pooled study results revealed significant differences for olanzapine/ fluoxetine combination (-12.7) versus fluoxetine (-9.0, p < .001) and olanzapine (-8.8, p < .001). Pooled remission rates were 27% for olanzapine/ fluoxetine combination, 17% for fluoxetine, and 15% for olanzapine. Adverse events were consistent with previous studies. Cholesterol mean change (mg/dL) was +15.1 for olanzapine/ fluoxetine combination, +0.8 for fluoxetine, and +2.7 for olanzapine. Mean weight change (kg) was +4.9 for olanzapine/fluoxetine combination, +0.4 for fluoxetine, and +5.5 for olanzapine. Nonfasting glucose mean change (mg/dL) was +11.4 for olanzapine/fluoxetine combination, +4.9 for fluoxetine, and +9.9 for olanzapine.

CONCLUSION

Patients with TRD (defined as treatment failure on 2 antidepressants) taking olanzapine/fluoxetine combination demonstrated significantly greater improvement in depressive symptoms than patients taking olanzapine or fluoxetine in 1 of 2 studies and in the pooled analysis. When considered within the context of all available evidence, olanzapine/fluoxetine combination is an efficacious therapy for patients with TRD.

CLINICAL TRIALS REGISTRATION

ClinicalTrials.gov identifier: NCT00035321.

摘要

目的

两项平行的、为期8周的双盲研究比较了奥氮平/氟西汀联合用药、奥氮平和氟西汀在难治性抑郁症（TRD）门诊患者中的疗效。

方法

难治性抑郁症定义为当前发作的抗抑郁药治疗失败的记录病史加上氟西汀治疗的预期失败。在8周的氟西汀导入期后，605名患有DSM-IV重度抑郁症且无反应的患者被随机分配到奥氮平/氟西汀联合用药组、奥氮平组或氟西汀组。主要结局指标是蒙哥马利-艾斯伯格抑郁评定量表（MADRS）从基线到终点的平均变化。该研究于2002年4月至2005年5月进行。

结果

双盲治疗8周后，研究1显示MADRS平均变化无统计学显著的治疗差异（奥氮平/氟西汀联合用药组：-11.0，氟西汀组：-9.4，奥氮平组：-10.5）。在研究2中，奥氮平/氟西汀联合用药组的MADRS改善程度（-14.5）显著高于氟西汀组（-8.6，p <.001）和奥氮平组（-7.0，p <.001）。汇总研究结果显示，奥氮平/氟西汀联合用药组（-12.7）与氟西汀组（-9.0，p <.001）和奥氮平组（-8.8，p <.001）之间存在显著差异。汇总缓解率奥氮平/氟西汀联合用药组为27%，氟西汀组为17%，奥氮平组为15%。不良事件与先前研究一致。胆固醇平均变化（mg/dL）奥氮平/氟西汀联合用药组为+15.1，氟西汀组为+0.8，奥氮平组为+2.7。平均体重变化（kg）奥氮平/氟西汀联合用药组为+4.9，氟西汀组为+0.4，奥氮平组为+5.5。非空腹血糖平均变化（mg/dL）奥氮平/氟西汀联合用药组为+11.4，氟西汀组为+4.9，奥氮平组为+9.9。