A meta-analysis of clinical trials comparing milnacipran, a serotonin–norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder

ContextOver the past few years, a number of studies have emerged suggesting that the treatment of major depressive disorder (MDD) with antidepressants which enhance both noradrenergic as well as serotonergic neurotransmission may result in higher response or remission rates than treatment with antidepressants which selectively enhance serotonergic neurotransmission.ObjectiveThe objective of this paper was to compare response rates among patients with MDD treated with either milnacipran, an antidepressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or a selective serotonin reuptake inhibitor (SSRI).Data sourcesMedline/Pubmed were searched. No year of publication or language limits were used.Study selectionDouble-blind, randomized clinical trials comparing milnacipran with an SSRI for the treatment of MDD.Data extractionData were extracted with the use of a pre-coded form.Data synthesisAnalyses were performed comparing response rates between the two antidepressant agents. Data from 6 reports involving a total of 1082 outpatients with MDD were identified and combined using a random-effects model. Patients randomized to treatment with milnacipran were as likely to experience clinical response as patients randomized to treatment with an SSRI according to the MADRS (RR = 1.04, 95% CI: 0.88–1.23, p = 0.533) or the HDRS (RR = 1.06, 95% CI: 0.90–1.24, p = 0.456) for the random effects model. Simply pooling MADRS-based response rates between the two agents revealed a 58.9% response rate for milnacipran and a 58.3% response rate for the SSRIs. Similarly, HDRS-based response rates were 59.7% and 57.5%. There was also no difference in overall discontinuation rates (RR = 0.93; 95% CI: 0.76–1.14; p = 0.506), the rate of discontinuation due to adverse events (RR = 0.77; 95% CI: 0.55–1.1; p = 0.157), or the rate of discontinuation due to inefficacy (RR = 0.98; 95% CI: 0.7–1.38; p = 0.95) between the two groups.ConclusionsThese results suggest that milnacipran and the SSRIs do not differ with respect to their overall efficacy in the treatment of MDD.