Norio Watanabe, MD, PhD; Ichiro M. Omori, MD, PhD; Atsuo Nakagawa, MD; Andrea Cipriani, MD; Corrado Barbui, MD; Hugh McGuire, MSc; Rachel Churchill, PhD; and Toshiaki A. Furukawa, MD, PhD; on behalf of the Multiple Meta-Analyses of New Generation Antidepressants (MANGA) Study Group
Objective: To 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 Sources: Studies 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 Selection: Twenty-five randomized controlled trials were
included.
Data Extraction: Two independent assessors examined the
quality of the trials and extracted data on an intention-to-treat basis.
Data Synthesis: The 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.
Conclusions: Although 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.
J Clin Psychiatry 2008;69(9):1404-1415
© Copyright 2008 Physicians Postgraduate Press, Inc.