Use of effect size to determine optimal dose of duloxetine in major depressive disorder

Abstract

Objective At effective doses, patients with major depressive disorder (MDD) treated with duloxetine have been found to experience significant symptom improvement as measured by HAMD 17 total score. In addition, duloxetine-treated patients have significantly higher remission and response rates compared with placebo. The objective of this analysis is to determine the optimal dose of duloxetine in MDD. Materials and methods Effect size for duloxetine 40 mg, 60 mg, 80 mg, and 120 mg per day were estimated using all 6 acute phase III clinical trials in patients with MDD. The tolerability of duloxetine 40 mg, 60 mg, 80 mg, and 120 mg were evaluated using pooled data from the 6 studies. The primary efficacy measure in all trials was the HAMD 17 total score, from which were determined the effect size for HAMD 17 change scores, response rates (50% reduction from baseline to endpoint), and remission rates (HAMD 17 total score ⩽7). Results A total of 1619 randomized patients were included in these studies, of which 632 were treated with placebo; 177 with duloxetine 40 mg/day; 251 with 60 mg/day; 363 with 80 mg/day; and 196 with 120 mg/day. An evaluation of increments in effect size between doses consistently showed that the most notable gain in effect size for efficacy was the 40–60 mg/day dosage range. All dosages from 60 to 120 mg were effective. The tolerability assessment indicated duloxetine at 40–120 mg/day is well tolerated. Furthermore, the initial doses of 40–80 mg/day were found to have comparable tolerability. Conclusions The effect size analyses demonstrate that duloxetine 40 mg has minimum efficacy, and that duloxetine 60–120 mg/day is effective in the treatment of patients with MDD. An initial dose less than 60 mg/day might provide better tolerability for some patients diagnosed with MDD.