• Norio Watanabe, Ichiro M Omori, Atsuo Nakagawa, Andrea Cipriani, Corrado Barbui, Hugh McGuire, Rachel Churchill, Toshiaki A Furukawa, and Multiple Meta-Analyses of New Generation Antidepressants (MANGA) Study Group.
• Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. noriow@med.nagoya-cu.ac.jp
• J Clin Psychiatry. 2008 Sep 1; 69 (9): 1404-15.

ObjectiveTo conduct a comprehensive, systematic review and meta-analysis of the efficacy and tolerability of mirtazapine over other antidepressants in the acute-phase treatment of major depression.Data SourcesStudies were initially identified through electronic searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register up to June 2006. The following search terms were used: depress*, dysthymi*, adjustment disorder*, mood disorder*, affective disorder, affective symptoms, and mirtazapine. No language restriction was imposed. The reference lists of the included studies, previous relevant systematic reviews, and trial registers were also hand searched. Pharmaceutical companies and experts in the field were contacted for more studies.Study SelectionTwenty-five randomized controlled trials were included.Data ExtractionTwo independent assessors examined the quality of the trials and extracted data on an intention-to-treat basis.Data SynthesisThe primary outcome measure was the relative risk (RR) of response (99% CIs) at the conclusion of acute-phase treatment. In relation to the early phase of treatment (at 2 weeks), there were no statistically significant differences between mirtazapine and the tricyclics in terms of the response (RR = 0.90, 99% CI = 0.69 to 1.18, p = .30 [8 trials contributed to this outcome]) or remission (RR = 0.87, 99% CI = 0.52 to 1.47, p = .50 [8 trials]) outcomes, but mirtazapine was superior to the selective serotonin reuptake inhibitors (SSRIs) in terms of both the response (RR = 1.36, 99% CI = 1.13 to 1.64, p < .0001 [12 trials]) and remission (RR = 1.68, 99% CI = 1.20 to 2.36, p < .0001 [12 trials]). In the subgroup analyses, mirtazapine significantly produced more response than paroxetine (RR = 2.02, 99% CI = 1.09 to 3.75, p = .003 [3 trials]) and venlafaxine (RR = 1.77, 99% CI = 1.08 to 2.89, p = .003 [2 trials]). At the end of acute-phase treatment (6-12 weeks, all trials), no significant differences were observed in the efficacy outcomes. No significant differences were observed between mirtazapine and the other antidepressants in terms of either the total number of dropouts due to any reason (21 trials) or the total number of dropouts due to the development of side effect (23 trials) during the trials.ConclusionsAlthough mirtazapine is likely to have a faster onset of action than SSRIs, no significant differences were observed at the end of 6 to 12 weeks' treatment. Clinicians should focus on other practically relevant considerations to tailor treatment to best fit the needs of individual patients.Copyright 2008 Physicians Postgraduate Press, Inc.

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