A Cochrane review included 16 RCTs with a total of 2277 subjects with major depression. Depression was either unipolar or bipolar. Milnacipran was compared with tricyclic antidepressives (TCA), mianserin and selective serotonine reuptake inhibitors with the mean length of the trials of 7 weeks. The efficacy data were evaluated with either 17, 21 or 24-item HAM-D for all the studies. Despite the size of this sample, the pooled 95% CIs 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.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment), indirectness (short follow-up) and imprecise results (limited study size for each comparison, wide confidence intervals)