The Efficacy and Safety of Mirtazapine and Fluoxetine for Depression: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

1. Anhui Medical University Provincial Hospital, Hefei 230001, China;2. West China Hospital of Sichuan University, Chinese Evidence-Based Medicine/Cochrane Centre, Chengdu 610041, China;3. Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China;

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Keywords：

Mirtazapine; Fluoxetine; Depression; Meta-analysis

DOI：

10.7507/1672-2531.20100385

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Objective 　To assess the efficacy and safety of mirtazapine and fluoxetine on depression.
Methods 　We searched The Cochrane Library (Issue 2, 2009), MEDLINE (1980 to Dec.2008), EMbase (1980 to Dec.2008), CBM (1980 to Dec.2008), VIP (1980 to Dec.2008), CNKI (1980 to Dec.2008) and Wanfang database (1980 to Dec.2008) to search randomized controlled trials (RCTs) comparing mirtazapine with fluoxetine for depression. The quality of the included trials was assessed and meta-analysis was conducted by RevMan 5.0 software.
Results 　Five RCTs involving 695 patients were included. The results of meta-analyses showed that: (1) After one-week treatment and two-week treatment, effectiveness of the mirtazapine group was significantly higher than that of the fluoxetine group [one-week treatment: RR=2.00, 95%CI (1.30, 3.10), P=0.002; two-week treatment: RR=1.49, 95%CI (1.08, 2.06), P=0.02]. But after six-week treatment, there was no significant difference of the efficacy between the mirtazapine and the fluoxetine groups with RR=1.21 and 95%CI 0.89 to 1.63 (P=0.23), and the cure rate of the mirtazapine group was a little higher than that of the fluoxetine group with RR=1.40 and 95%CI 1.09 to 1.80 (P=0.009). (2) Side reaction: The somnolence and weight gain rates of the mirtazapine group was higher than those of the fluoxetine group with RR=1.78 and 95%CI 1.18 to 2.70 (P=0.006) and RR=5.91 and 95%CI 2.21 to 15.83 (P=0.000 4). But fluoxetine more easily induced nausea and insomnia with RR=0.47 and 95%CI 0.31 to 0.71 (P=0.000 3); RR=0.39 and 95%CI 0.17 to 0.89 (P=0.03) than mirtazapine. And the other common side reactions were all not significantly different between the two groups (P gt;0.05).
Conclusion 　Mirtazapine is more effective than fluoxetine and works faster. Mirtazapine could more easily induce somnolence and weight gain, and is with lower nausea or insomnia rate when compared with fluoxetine. And there is no significant difference in comparison of other common side reactions.

Citation： ZHOU Ran,XU Weiping,WANG Li,XU Tingjuan,HU Shilian,YAN Guang,WEI Wei,LI Youping. The Efficacy and Safety of Mirtazapine and Fluoxetine for Depression: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2010, 10(2): 196-202. doi: 10.7507/1672-2531.20100385 Copy

1.	Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020:Global Burden of Disease Study.Lancet, 1997, 349(9064): 1498-1504.
2.	Sonawalla SB, Fava M. Severe depression:is there a best approach? CNS Drugs, 2001, 15(10): 765-776.
3.	Thomas CM, Morris S. Cost of depression among adults in England in 2000. Br J Psychiatry, 2003, 183: 514-519.
4.	Wang PS, Simon G, Kesler RC, et al. The economic burden of depression and the cost-effectiveness of treatment. Int J Methods Psychiatry Res, 2003, 12(1): 22-33.
5.	de Boer T. The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission. Int Clin Psychopharmacol, 1995, 10(Suppl 4): 19-23.
6.	Benkert O, Szegedi A, Kohnen R, et al. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry, 2000, 61(9): 656-663.
7.	Kasper S. Clinical efficacy of mirtazapine:a review of meta-analyses of pooled data. Int Clin Psychopharmacol, 1995, 10(Suppl 4): 25-35.
8.	Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and meta-analysis. J Clin Psychiatry, 2008, 69(9): 1404-1415.
9.	Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry, 1960, 23: 56-62.
10.	Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials:is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
11.	Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA, 1995, 273(5): 408-412.
12.	Amini H, Aghayan S, Jalili SA, et al. Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a doubleblind, randomized trial. J Clin Pharm Ther, 2005, 30(2): 133-138.
13.	Versiani M, Moreno R, Ramakers-van Moorsel CJ, et al. Comparative Efficacy Antidepressants Study Group.Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs, 2005, 19(2): 137-146.
14.	Wheatley DP, van Moffaert M, Timmerman L, et al. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine- Fluoxetine Study Group. J Clin Psychiatry, 1998, 59(6): 306-312.
15.	Hong CJ, Hu WH, Chen CC, et al. A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks’ treatment with mirtazapine or fluoxetine in depressed Chinese patients. J Clin Psychiatry, 2003, 64(8): 921-926v.
16.	张纪水, 刘铁桥, 赵靖平, 等. 米氮平与氟西汀治疗抑郁症的对照研究. 中国临床康复, 2003, 7(30): 4102-4104.
17.	Winokur A, DeMartinis NA 3rd, McNally DP, et al. Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. J Clin Psychiatry, 2003, 64(10): 1224-1229.
18.	de Boer T. The pharmacologic profile of mirtazapine. J Clin Psychiatry, 1996, 57(Suppl 4): 19-25.
19.	de Boer T, Nefkens F, Van Helvoirt A, et al. The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo. Eur J Pharmacol, 1994, 253(1-2): R5-6.
20.	Haddjeri N, Blier P, de Montigny C, et al. Noradrenergic modulation of central serotonergic neurotransmission:acute and long-term actions of mirtazapine. Int Clin Psychopharmacol, 1995, (10 Suppl 4): 11-7.
21.	Shen J, Chung SA, Kayumov L, et a1. Polysomographic and symptomatological analyses of major depressive disorder patients treated with mirtazapine. Can J Psychiatry, 2006, 51(1): 27-34.
22.	Schmid DA, Wiehniak A, Uhr M, et a1. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, Prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacology, 2006, 31(4): 832-844.
23.	Herman JB, Brotman AW, Pollack MH, et al. Fluoxetine-induced sexual dysfunction. J Clin Psychiatry, 1990, 51(1): 25-27.
24.	Kline MD. Fluoxetine and anorgasmia. Am J Psychiatry, 1989, 146(6): 804-805.
25.	Musher JS. Anorgasmia with the use of fluoxetine. Am J Psychiatry, 1990, 147(7): 948.
26.	Goodnick PJ, Kremer C, Wingard P, et al. Weight change during mirtazapine therapy. Prim Psychiatry, 1998, 3: 103-108.
27.	Gartlehner G, Gaynes BN, Hansen RA, et al. Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. Ann Intern Med, 2008, 149(10): 734-750.

1. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020:Global Burden of Disease Study.Lancet, 1997, 349(9064): 1498-1504.
2. Sonawalla SB, Fava M. Severe depression:is there a best approach? CNS Drugs, 2001, 15(10): 765-776.
3. Thomas CM, Morris S. Cost of depression among adults in England in 2000. Br J Psychiatry, 2003, 183: 514-519.
4. Wang PS, Simon G, Kesler RC, et al. The economic burden of depression and the cost-effectiveness of treatment. Int J Methods Psychiatry Res, 2003, 12(1): 22-33.
5. de Boer T. The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission. Int Clin Psychopharmacol, 1995, 10(Suppl 4): 19-23.
6. Benkert O, Szegedi A, Kohnen R, et al. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry, 2000, 61(9): 656-663.
7. Kasper S. Clinical efficacy of mirtazapine:a review of meta-analyses of pooled data. Int Clin Psychopharmacol, 1995, 10(Suppl 4): 25-35.
8. Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and meta-analysis. J Clin Psychiatry, 2008, 69(9): 1404-1415.
9. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry, 1960, 23: 56-62.
10. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials:is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
11. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA, 1995, 273(5): 408-412.
12. Amini H, Aghayan S, Jalili SA, et al. Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a doubleblind, randomized trial. J Clin Pharm Ther, 2005, 30(2): 133-138.
13. Versiani M, Moreno R, Ramakers-van Moorsel CJ, et al. Comparative Efficacy Antidepressants Study Group.Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients. CNS Drugs, 2005, 19(2): 137-146.
14. Wheatley DP, van Moffaert M, Timmerman L, et al. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine- Fluoxetine Study Group. J Clin Psychiatry, 1998, 59(6): 306-312.
15. Hong CJ, Hu WH, Chen CC, et al. A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks’ treatment with mirtazapine or fluoxetine in depressed Chinese patients. J Clin Psychiatry, 2003, 64(8): 921-926v.
16. 张纪水, 刘铁桥, 赵靖平, 等. 米氮平与氟西汀治疗抑郁症的对照研究. 中国临床康复, 2003, 7(30): 4102-4104.
17. Winokur A, DeMartinis NA 3rd, McNally DP, et al. Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. J Clin Psychiatry, 2003, 64(10): 1224-1229.
18. de Boer T. The pharmacologic profile of mirtazapine. J Clin Psychiatry, 1996, 57(Suppl 4): 19-25.
19. de Boer T, Nefkens F, Van Helvoirt A, et al. The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo. Eur J Pharmacol, 1994, 253(1-2): R5-6.
20. Haddjeri N, Blier P, de Montigny C, et al. Noradrenergic modulation of central serotonergic neurotransmission:acute and long-term actions of mirtazapine. Int Clin Psychopharmacol, 1995, (10 Suppl 4): 11-7.
21. Shen J, Chung SA, Kayumov L, et a1. Polysomographic and symptomatological analyses of major depressive disorder patients treated with mirtazapine. Can J Psychiatry, 2006, 51(1): 27-34.
22. Schmid DA, Wiehniak A, Uhr M, et a1. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, Prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacology, 2006, 31(4): 832-844.
23. Herman JB, Brotman AW, Pollack MH, et al. Fluoxetine-induced sexual dysfunction. J Clin Psychiatry, 1990, 51(1): 25-27.
24. Kline MD. Fluoxetine and anorgasmia. Am J Psychiatry, 1989, 146(6): 804-805.
25. Musher JS. Anorgasmia with the use of fluoxetine. Am J Psychiatry, 1990, 147(7): 948.
26. Goodnick PJ, Kremer C, Wingard P, et al. Weight change during mirtazapine therapy. Prim Psychiatry, 1998, 3: 103-108.
27. Gartlehner G, Gaynes BN, Hansen RA, et al. Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. Ann Intern Med, 2008, 149(10): 734-750.

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The Efficacy and Safety of Mirtazapine and Fluoxetine for Depression: A Meta-analysis

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