Effectiveness and Safety of Olanzapine Combined with Fluoxetine for Refractory Depression: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Xiaohua ¹ , GUO Xiaodong ¹ ,  LIU Meng ²

1. Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China;2. Lanzhou University Library, Lanzhou 730000, China;

Corresponding author：

LIU Meng, Email: lium2000@163.com

Keywords：

Olanzapine; Fluoxetine; Refractory depression; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.20100551

Video：

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Objective 　To evaluate the effectiveness and safety of both olanzapine combined with fluoxetine (combination therapy) and fluoxetine (monotherapy) for refractory depression.
Methods 　According to the computer retrieval from PubMed (1966 to September 2009), Cochrane Library (Issue 3, 2009), EMbase (1974 to September 2009), SCI (1974 to September 2009), CNKI (1994 to September 2009), CBM (1978 to September 2009), CSJD (1989 to September 2009) and Wanfang Database (1997 to September 2009), and the manual retrieval from related journals and conference proceedings were conducted, to include randomized controlled trials of comparison in between olanzapine combined with fluoxetine and fluoxetine in treating refractory depression. We collected the valid data after assessing the methodology quality of included studies on the basis of Jadad scoring standard, and conducted meta-analysis with RevMan 5.0 software. Results　 A total of 7 studies with 1 230 patients were included. The meta-analysis showed that, there was no significant difference between two groups about the scores of HAMA (Hamilton Anxiety Scale) at the end of the 1st week, but the olanzapine combined with fluoxetine in trial group was much better for relieving anxiety situation compared to fluoxetine in control group at the end of the 2nd, 4th, 8th and 12th week. In accordance with the scores of CGI (Clinical Global Impression Scale), there was no significant difference at the end of 2nd and 4th week after treatment, but there was a significant difference at the end of 8th and 12th week. As to the changes of MADRS (Montgomery and Asberg Depression Rating Scale), the trial group was much distinct than control group at the end of the 1st, 2nd, 4th and 8th week. In summary, the clinical effect of trial group was superior to that of control group, and there was no significant difference in adverse reactions between two groups (RR=1.10, 95%CI 0.99 to 1.23).
Conclusion　 Current evidence shows that, the clinical effect and safety of olanzapine combined with fluoxetine in treating refractory depression is obviously superior to that of fluoxetine.

Citation： WANG Xiaohua,GUO Xiaodong,LIU Meng. Effectiveness and Safety of Olanzapine Combined with Fluoxetine for Refractory Depression: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2010, 10(9): 1102-1109. doi: 10.7507/1672-2531.20100551 Copy

1.	Murry C, Lopez A. The Global burden of mortality and disability from disease, injuries, and risk factors in1990 and 2020. Cambridge, MA: Harvard University Press, 1996, 232.
2.	Bobo WV, Shelton RC. Olanzapine and fluoxetine combination therapy for treatment-resistant depression: review of efficacy, safety, and study design issues. Neuropsychiatr Dis Treat, 2009, 5: 369-383.
3.	Sackeim HA. The definition and meaning of treatment resistant depression. J Clin Psychiatry, 2001, 62(Suppl 16): 10-17.
4.	Beasley CM Jr, Stauffer VL, Liu-Seifert H, et al. All-cause treatment discontinuation in schizophrenia during treatment with olanzapine relative to other antipsychotics: an integrated analysis. Clin Psyehopharmacol, 2007, 27(3): 252-258.
5.	刘玉林. 氟西汀治疗老年高血压病并发抑郁症28例. 山东医药, 2005, 45(32): 51-52.
6.	Thase ME, Corya SA, Osuntokun O, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder.J Clin Psychiatry, 2007, 68(2): 224-236.
7.	王彬, 胡峻梅, 李宝花, 等. 氟西汀合并奥氮平治疗难治性抑郁症对照研究. 山东精神医学, 2006, 19(2): 87-89.
8.	胡德凤, 陈梅芳, 陶云海. 奥氮平及氟西汀联合治疗难治性抑郁症的疗效观察. 浙江实用医学, 2008, 13(2): 117-118.
9.	Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry, 2001, 158(1): 131-134.
10.	Shelton RC, Williamson DJ, Corya SA, et al. Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance. J Clin Psychiatry, 2005, 66(10): 1289-1297.
11.	Corya SA, Williamson D, Sanger TM, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression.Depress Anxiety, 2006, 23(6): 364-372.
12.	Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry, 1960, 23: 56-62.
13.	中华医学会精神科分会. 中国精神障碍分类与诊断标准(CCMD-3). 济南: 山东科学技术出版社, 2001, 4.
14.	Jadad AR, Moore A, Carroll D, et al. Assessing the quality of reports of randomized clinical trails: Is blinding necessary? Control Clin Trails, 1996, 17(1): 1-12.
15.	李鹤展, 张亚林, 张迎黎, 等. 氟西汀合并奥氮平治疗难治性抑郁症的双盲对照研究. 山东精神医学, 2006, 19(2): 85-86.
16.	沈渔邮, 主编. 精神病学. 第4版. 北京: 人民卫生出版社, 2002, 429.
17.	陈琦, 汤宜朗. 新型非典型抗精神病药治疗难治性精神分裂症. 国外医学精神病学分册, 2001, 2: 76.
18.	陈静, 陆峥. 非典型抗精神病药治疗难治性抑郁症. 上海精神医学, 2004, 16(5): 301-303.
19.	秦启亮, 刘炳伦, 张成华. 奥氮平的药理与临床研究. 国外医学精神病学分册, 1999, 2: 72.
20.	王骞, 李胜书, 王克. 奥氮平辅助治疗难治性抑郁症的观察. 山东精神医学, 2005, 18(1): 48-49.
21.	舒良, 刘平. 新型非典型抗精神病药奥氮平. 中华精神科杂志, 1999, 32(2): 123.
22.	王克, 王东明, 姜桂兰, 等. 奥氮平辅助治疗难治性抑郁症效果观察. 齐鲁医学杂志, 2007, 22(5): 457.
23.	Shelton RC. The use of antidepressants in novel combination therapies. J Clin Psychiatry, 2003, 64 (Suppl 2): 14-18.
24.	Schatzberg AF. New approaches to managing psychotic depression. J Clin Psychiatry, 2003, 64 (Suppl 1): 19-23.

1. Murry C, Lopez A. The Global burden of mortality and disability from disease, injuries, and risk factors in1990 and 2020. Cambridge, MA: Harvard University Press, 1996, 232.
2. Bobo WV, Shelton RC. Olanzapine and fluoxetine combination therapy for treatment-resistant depression: review of efficacy, safety, and study design issues. Neuropsychiatr Dis Treat, 2009, 5: 369-383.
3. Sackeim HA. The definition and meaning of treatment resistant depression. J Clin Psychiatry, 2001, 62(Suppl 16): 10-17.
4. Beasley CM Jr, Stauffer VL, Liu-Seifert H, et al. All-cause treatment discontinuation in schizophrenia during treatment with olanzapine relative to other antipsychotics: an integrated analysis. Clin Psyehopharmacol, 2007, 27(3): 252-258.
5. 刘玉林. 氟西汀治疗老年高血压病并发抑郁症28例. 山东医药, 2005, 45(32): 51-52.
6. Thase ME, Corya SA, Osuntokun O, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder.J Clin Psychiatry, 2007, 68(2): 224-236.
7. 王彬, 胡峻梅, 李宝花, 等. 氟西汀合并奥氮平治疗难治性抑郁症对照研究. 山东精神医学, 2006, 19(2): 87-89.
8. 胡德凤, 陈梅芳, 陶云海. 奥氮平及氟西汀联合治疗难治性抑郁症的疗效观察. 浙江实用医学, 2008, 13(2): 117-118.
9. Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry, 2001, 158(1): 131-134.
10. Shelton RC, Williamson DJ, Corya SA, et al. Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance. J Clin Psychiatry, 2005, 66(10): 1289-1297.
11. Corya SA, Williamson D, Sanger TM, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression.Depress Anxiety, 2006, 23(6): 364-372.
12. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry, 1960, 23: 56-62.
13. 中华医学会精神科分会. 中国精神障碍分类与诊断标准(CCMD-3). 济南: 山东科学技术出版社, 2001, 4.
14. Jadad AR, Moore A, Carroll D, et al. Assessing the quality of reports of randomized clinical trails: Is blinding necessary? Control Clin Trails, 1996, 17(1): 1-12.
15. 李鹤展, 张亚林, 张迎黎, 等. 氟西汀合并奥氮平治疗难治性抑郁症的双盲对照研究. 山东精神医学, 2006, 19(2): 85-86.
16. 沈渔邮, 主编. 精神病学. 第4版. 北京: 人民卫生出版社, 2002, 429.
17. 陈琦, 汤宜朗. 新型非典型抗精神病药治疗难治性精神分裂症. 国外医学精神病学分册, 2001, 2: 76.
18. 陈静, 陆峥. 非典型抗精神病药治疗难治性抑郁症. 上海精神医学, 2004, 16(5): 301-303.
19. 秦启亮, 刘炳伦, 张成华. 奥氮平的药理与临床研究. 国外医学精神病学分册, 1999, 2: 72.
20. 王骞, 李胜书, 王克. 奥氮平辅助治疗难治性抑郁症的观察. 山东精神医学, 2005, 18(1): 48-49.
21. 舒良, 刘平. 新型非典型抗精神病药奥氮平. 中华精神科杂志, 1999, 32(2): 123.
22. 王克, 王东明, 姜桂兰, 等. 奥氮平辅助治疗难治性抑郁症效果观察. 齐鲁医学杂志, 2007, 22(5): 457.
23. Shelton RC. The use of antidepressants in novel combination therapies. J Clin Psychiatry, 2003, 64 (Suppl 2): 14-18.
24. Schatzberg AF. New approaches to managing psychotic depression. J Clin Psychiatry, 2003, 64 (Suppl 1): 19-23.

Chinese Journal of Evidence-Based Medicine

Effectiveness and Safety of Olanzapine Combined with Fluoxetine for Refractory Depression: A Systematic Review

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