Objective: Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD).
Methods: In this randomized, double-blind trial, patients age > or =18 meeting DSM-IV criteria for MDD were randomized to placebo (N=99), duloxetine 80 mg/day (N=93), duloxetine 120 mg/day (N=103), or paroxetine 20 mg/day (N=97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD(17)) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed. Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events (TEAEs), vital signs, and weight. The Arizona sexual experiences scale was used to assess sexual functioning. Patients who had a > or =30% reduction from baseline in the HAMD(17) total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase; efficacy and safety/tolerability outcomes were assessed during continuation treatment.
Results: More than 87% of patients completed the acute phase in each treatment group. Duloxetine-treated patients (both doses) showed significantly greater improvement (P<0.05) in the HAMD(17) total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo (P=0.089) on mean change on the HAMD(17). Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. HAMD(17) mean change data from this study and an identical sister study were pooled as defined a priori for the purposes of performing a non-inferiority test versus paroxetine. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine. TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases.
Conclusions: The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated. Tolerability, as measured by TEAEs, and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD.