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A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder

Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, gpapakostas{at}partners.org

CH Homberger

Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

M. Fava

Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Over the past few years, a number of studies have suggested that the treatment of major depressive disorder (MDD) with anti-depressants enhancing both noradrenergic as well as serotonergic neurotransmission may result in higher response or remission rates than treatment with anti-depressants selectively enhancing serotonergic neurotransmission. The objective of this paper was to compare response rates among patients with MDD treated with either mirtazapine, an anti-depressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs). Medline/Pubmed were searched. No year of publication limits were used. Double-blind, randomized clinical trials comparing mirtazapine with an SSRI for the treatment of MDD. Data were extracted with the use of a pre-coded form. Analyses were performed comparing response rates between the two anti—depressant agents. Data from 10 reports involving a total of 1904 outpatients with MDD were identified and combined using a random-effects model. Patients randomized to treatment with mirtazapine were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR = 1.07; 95% CI: 0.96—1.2, P = 0.181). Simply pooling response rates between the two agents revealed a 67.1% response rate for mirtazapine and a 62.1% response rate for the SSRIs. There was no difference in overall discontinuation rates (RR = 1.1; 95% CI: 0.7—1.5; P = 0.550), discontinuation rates due to adverse events (RR = 0.9; 95% CI: 0.6—1.2; P = 0.497), or discontinuation rates due to lack of efficacy (RR = 0.9; 95% CI: 0.4—2.0; P = 0.871) between the two groups. Fewer mirtazapine-treated patients complained of insomnia (RR = 0.5; 95% CI: 0.3—0.9; P = 0.017), nausea (RR = 0.3; 95% CI: 0.3—0.5; P < 0.0001), whereas fewer SSRI-treated patients complained of fatigue (RR = 1.5; 95% CI: 1.1—2.4; P = 0.028), excessive sleepiness (RR = 1.3; 95% CI: 1.1—1.7; P = 0.020), weight-gain (RR = 3.8; 95% CI: 2.3—6.4; P < 0.0001) or dry mouth (RR = 1.8; 95% CI: 1.3—2.4; P < 0.0001) during the course of treatment. These results suggest that mirtazapine and the SSRIs differ with respect to their side-effect profile but not their overall efficacy in the treatment of MDD.

Key Words: mirtazapine • SSRI • major • depressive • disorder • response

This version was published on November 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 8, 843-848 (2008)
DOI: 10.1177/0269881107083808


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