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Summary   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.

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