It has been proposed that
serotonin and norepinephrine reuptake inhibitors (
SNRIs) may result in higher remission rates of
major depressive disorder than
therapy with
selective serotonin reuptake inhibitors (
SSRIs). To test this hypothesis, a meta-analysis of individual patient data (N = 1833) was performed for the complete set of 6 phase II/III studies that compared
duloxetine (fixed doses; range, 40-120 mg/d) with 2
SSRIs (
paroxetine or
fluoxetine; 20 mg/d) in outpatients with
major depressive disorder. Remission was defined as an end point score of less than or equal to 7 on the 17-item Hamilton Rating Scale for Depression (HAMD17); alternate outcome criteria were also examined, as were remission rates among the 1044 patients with moderate-to-severe depression (HAMD17 total score greater than or equal to 19). The HAMD17 remission rates were 40.3% (351/871), 38.3% (162/423), and 28.4% (144/507) for
duloxetine, the 2
SSRIs, and placebo, respectively. Both active treatments were superior to placebo; the difference between
duloxetine and
SSRIs was not statistically significant. Similar findings were observed for alternate outcomes.
Duloxetine therapy was significantly more effective than
therapy with the 2
SSRIs for patients with more severe depression, with remission rates of 35.9% (183/510) versus 28.6% (70/245) (P = 0.046). A secondary analysis of dose-response relationships indicated that this advantage was not attributable to the studies using higher doses of
duloxetine. Thus, whereas
duloxetine and the 2
SSRIs were comparably efficacious overall,
therapy with the
serotonin and
norepinephrine reuptake inhibitor resulted in a significantly higher remission rate among patients with moderate-to-severe depression.