Efficacy and safety of duloxetine 60 mg once daily in major depressive disorder: a review with expert commentary

Abstract

Objective: Major depressive disorder (MDD) is a significant public health concern and challenges health care providers to intervene with appropriate treatment. This article provides an overview of efficacy and safety information for duloxetine 60 mg/day in the treatment of MDD, including its effect on painful physical symptoms (PPS).

Design: A literature search was conducted for articles and pooled analyses reporting information regarding the use of duloxetine 60 mg/day in placebo-controlled trials.

Setting: Placebo-controlled, active-comparator, short- and long-term studies were reviewed.

Participants: Adult (≥18 years) patients with MDD.

Measurements: Effect sizes for continuous outcome (change from baseline to endpoint) and categorical outcome (response and remission rates) were calculated using the primary measures of 17-item Hamilton Rating Scale for Depression (HAMD-17) or Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The Brief Pain Inventory and Visual Analogue Scales were used to assess improvements in PPS. Glass estimation method was used to calculate effect sizes, and numbers needed to treat (NNT) were calculated based on HAMD-17 and MADRS total scores for remission and response rates. Safety data were examined via the incidence of treatment-emergent adverse events and by mean changes in vital-sign measures.

Results: Treatment with duloxetine was associated with small-to-moderate effect sizes in the range of 0.12 to 0.72 for response rate and 0.07 to 0.65 for remission rate. NNTs were in the range of 3 to 16 for response and 3 to 29 for remission. Statistically significant improvements (p≤0.05) were observed in duloxetine-treated patients compared to placebo-treated patients in PPS and quality of life. The safety profile of the 60-mg dose was consistent with duloxetine labeling, with the most commonly observed significant adverse events being nausea, dry mouth, diarrhea, dizziness, constipation, fatigue, and decreased appetite.

Conclusion: These results reinforce the efficacy and tolerability of duloxetine 60 mg/day as an effective short- and long-term treatment for adults with MDD. The evidence of the independent analgesic effect of duloxetine 60 mg/day supports its use as a treatment for patients with PPS associated with depression. This review is limited by the fact that it included randomized clinical trials with different study designs. Furthermore, data from randomized controlled trials may not generalize well to real clinical practice.

Keywords: duloxetine; effect size; major depressive disorder; painful physical symptoms; quality of life; safety and tolerability.

Figure 1

Effect size based on mean change in MMRM analysis at last visit using HAMD-17 total score for Studies 1 to 6 (closed circles). MADRS was utilized for Studies 7 to 9 (open circles). For the Japanese study, effect size for the 60-mg dose was based on change from baseline to 6 weeks (LOCF), which was the secondary efficacy analysis of the study. Abbreviations HAMD-17, 17-item Hamilton Rating Scale for Depression; LOCF, last observation carried forward; MADRS, Montgomery-Åsberg Depression Rating Scale; MMRM, mixed-model repeated measure. doi: 10.7573/dic.212245.f001

Figure 2

Effect size for 50% response rate based on CAT_MMRM analysis at last visit using HAMD-17 total score, Studies 1 to 6 (closed circles). MADRS total score was used for Studies 7 to 9 (open circles). Abbreviations CAT_MMRM, categorical MMRM; HAMD-17, 17-item Hamilton Rating Scale for Depression; LOCF, last observation carried forward; MADRS, Montgomery-Åsberg Depression Rating Scale; MMRM, mixed-model repeated measure. doi: 10.7573/dic.212245.f002

Figure 3

Effect size for remission rate based on CAT_MMRM analysis at last visit using HAMD-17 total score, Studies 1 to 6 (closed circles). MADRS total score ≤12 was used for Studies 7 to 9 (open circles). Abbreviations CAT_MMRM, categorical MMRM; HAMD-17, 17-item Hamilton Rating Scale for Depression; MADRS, Montgomery-Åsberg Depression Rating Scale; MMRM, mixed-model repeated measure. doi: 10.7573/dic.212245.f003

Figure 4

NNT with 95% CI for response rates based on CAT_MMRM using HAMD-17 total score for Studies 1 to 6 (closed circles). MADRS total score was used for Studies 7 to 9 (open circles). Abbreviations CAT_MMRM, categorical MMRM; CI, confidence interval; HAMD-17, 17-item Hamilton Rating Scale for Depression; MADRS, Montgomery-Åsberg Depression Rating Scale; MMRM, mixed-model repeated measure; NNT, numbers needed to treat. doi: 10.7573/dic.212245.f004

Figure 5

NNTs for remission rate based on CAT_MMRM using HAMD-17 total score for Studies 1 to 6 (closed circles). MADRS total score ≤12 was used for Studies 7 to 9 (open circles). Abbreviations CAT_MMRM, categorical MMRM; HAMD-17, 17-item Hamilton Rating Scale for Depression; MADRS, Montgomery-Åsberg Depression Rating Scale; MMRM, mixed-model repeated measure; NNT, numbers needed to treat. doi: 10.7573/dic.212245.f005