Milnacipran versus other antidepressive agents for depression

Major depression, also known as major depressive disorder or unipolar depression, is a common mental disorder characterised by a combination of symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy pleasurable activities. An episode of major depression may occur only once in a person's lifetime, but more often, it recurs throughout a person's life.

Antidepressant drugs are frequently used as first-line treatment for major depression in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor, is one of the antidepressant drugs that clinicians use for routine depression care in some countries. This systematic review investigated the efficacy, acceptability and tolerability of milnacipran compared to that of other antidepressive agents in the acute phase treatment of major depression. A total of 16 randomised controlled trials (2277 participants) were included in this review. When we brought together the results of approximately 2000 patients, we were unable to say whether milnacipran is better, worse or the same when compared to other antidepressive agents used in practice in terms of efficacy, acceptability and tolerability. However, there is some evidence that fewer people taking milnacipran stop taking the drug ('drop out') due to side effects and fewer people taking milnacipran experience side effects such as sleepiness, dry mouth or constipation than do people who take tricyclic antidepressants.

Authors' conclusions: 

Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression.

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Background: 

Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs are frequently used as first-line treatment in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor (SNRI), is one of the antidepressant drugs that clinicians use for routine depression care.

Objectives: 

To assess the evidence for the efficacy, acceptability and tolerability of milnacipran in comparison with tricyclic antidepressants (TCAs), heterocyclics, SSRIs and other newer antidepressive agents in the acute-phase treatment of major depression.

Search strategy: 

The Cochrane Collaboration Depression, Anxiety & Neurosis review group Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) were electronically searched in August 2008. References of relevant trials and other reviews were also checked. Trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished trials were hand-searched in 2007. All relevant authors were contacted for supplemental data. No language restriction was applied.

Selection criteria: 

Randomised controlled trials comparing milnacipran with any other active antidepressive agents (including non-conventional agents such as herbal products like hypericum) as monotherapy in the acute phase of major depression were selected.

Data collection and analysis: 

Two reviewers independently checked eligibility, assessed methodological quality and extracted data from the eligible trials using a standardised data extraction form. The number of participants who responded to treatment or those who achieved remission were calculated on an intention-to-treat basis. Random-effects meta-analyses were conducted, combining data from the included trials.

Main results: 

A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressive agents. However, compared with TCAs, patients taking milnacipran were associated with fewer dropouts due to adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence to suggest that patients taking milnacipran experienced fewer adverse events of sleepiness/ drowsiness, dry mouth or constipation compared with TCAs.

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