Changes in energy during treatment of depression: an analysis of duloxetine in double-blind placebo-controlled trials

Abstract

Aims: The aim of this study was to assess how quickly and effectively duloxetine improves energy compared with placebo in patients with major depressive disorder (MDD).

Methods: Data from 10 randomised, double-blind, placebo-controlled clinical trials examining duloxetine (40-60 mg/day) vs. placebo in patients diagnosed with MDD were analysed. Change from baseline at Week 1 through Week 8 in Hamilton Depression Rating Scale (HAM-D) retardation subscale score (Item 1 - depressed mood, Item 7 - work and activities, Item 8 - retardation and Item 14 - genital symptoms) was assessed with mixed model repeated measures analysis. Positive predictive values and negative predictive values were calculated for predictor analysis.

Results: Patients treated with duloxetine (N = 1522) experienced statistically significantly (p ≤ 0.05) greater reductions in HAM-D retardation subscale scores vs. placebo (N = 1180) starting at Week 1 throughout Week 8 of treatment. Of the patients with early energy improvement (≥ 20% reduction in HAM-D retardation subscale scores) at Week 1, 48% achieved remission (HAM-D total score ≤ 7) at Week 8; 48% and 46% of patients who experienced early energy improvement at Weeks 2 and 4, respectively, achieved remission at Week 8.

Discussion: We demonstrated that treatment with duloxetine, quickly and with increasing magnitude over treatment time, improves low energy symptoms. As early as 1 week after starting treatment with duloxetine, improvement of low energy may serve as a predictor of remission at end-point.

Conclusions: Treatment with duloxetine improves energy in patients with MDD and early response in retardation may serve as a modest predictor of remission at end-point.

Clinical trials registration: ClinicalTrials.gov. Study Identifiers: NCT00036335; NCT00073411; NCT00406848 and NCT00536471. Studies HMAQa, HMAQb, HMATa, HMATb, HMBHa and HMBHb predate the registration requirement.

Data posting: ClinicalTrials.gov. Study Identifiers: NCT00406848; NCT00536471.

Figure 1

LSMean Changes of HAM-D Retardation Subscale Scores. The efficacy of duloxetine on HAM-D retardation subscale score was examined in comparison to placebo. The HAM-D retardation subscale consists of the following four items: Item 1 – depressed mood, Item 7 – work and activities, Item 8 – retardation, Item 14 – genital symptoms. These analyses were performed with MMRM. *p < 0.05, **p < 0.001, ***p < 0.0001. HAM-D, Hamilton Depression Rating Scale; LSMean, least squares mean; MMRM, mixed model repeated measures; n, number of patients

Figure 2

LSMean Score Changes of Individual Items of the HAM-D Retardation Subscale. LSMean changes of Item 1 – depressed mood (A), Item 7 – work and activities (B), Item 8 – retardation (C) and Item 14 – genital symptoms (D) are shown. *p < 0.05, **p < 0.001, ***p < 0.0001. MMRM analysis. Numbers of patients per treatment group and time point are identical to Figure1. HAM-D, Hamilton Depression Rating Scale; LSMean, least squares mean; MMRM, mixed model repeated measures

Figure 3

First onset of sustained improvement of energy. First onset of sustained improvement of energy was defined as the first time point when HAM-D retardation subscale score was reduced by ≥ 20% and the reduction was maintained throughout day 70 of treatment. The effect of duloxetine treatment on the first onset of sustained improvement of energy was compared with placebo by Cox proportional hazard model and Kaplan–Meier curve. CI, confidence interval; HAM-D, Hamilton Depression Rating Scale

Figure 4

HAM-D retardation subscale and total score changes in high and low retardation patients. (A) Baseline to week 8 HAM-D retardation subscale score changes – last-observation-carried-forward analysis. (B) Baseline to week 8 HAM-D total score changes – last-observation-carried-forward analysis. The effect of baseline energy levels on week 8 (LOCF) HAM-D retardation subscale score changes (A) and HAM-D total score changes (B) were analysed. Patients were grouped into high retardation (HAM-D retardation subscale score ≥ 8 at baseline) and low retardation (HAM-D retardation subscale score < 8 at baseline) subgroups. These analyses were performed by ANCOVA. **p < 0.01, ***p < 0.001. ANCOVA, analysis of covariance; HAM-D, Hamilton Depression Rating Scale; LSMean, least squares mean; n, number of patients