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

E Harada, M Kato, S Fujikoshi, M M Wohlreich, L Berggren, H Tokuoka, E Harada, M Kato, S Fujikoshi, M M Wohlreich, L Berggren, H Tokuoka

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.

© 2015 Eli Lilly Japan K.K. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Figures

Figure 1
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
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
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
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  < 0.01, ***p < 0.001. ANCOVA, analysis of covariance; HAM-D, Hamilton Depression Rating Scale; LSMean, least squares mean; n, number of patients

References

    1. Kennedy SH. Core symptoms of major depressive disorder: relevance to diagnosis and treatment. Dialogues Clin Neurosci. 2008;10:271–7.
    1. Joliat MJ, Brown EB, Miner CM. Changes in energy after switching from daily citalopram, paroxetine, or sertraline to once-weekly fluoxetine. J Clin Psychopharmacol. 2004;24:464–7.
    1. Judge R, Plewes JM, Kumar V, Koke SC, Kopp JB. Changes in energy during treatment of depression: an analysis of fluoxetine in double-blind, placebo-controlled trials. J Clin Psychopharmacol. 2000;20:666–72.
    1. Maurice-Tison S, Verdoux H, Gay B, Perez P, Salamon R, Bourgeois ML. How to improve recognition and diagnosis of depressive syndromes using international diagnostic criteria. Br J Gen Pract. 1998;48:1245–6.
    1. Tylee A, Gastpar M, Lepine JP, Mendlewicz J. DEPRES II (Depression Research in European Society II): a patient survey of the symptoms, disability and current management of depression in the community. DEPRES Steering Committee. Int Clin Psychopharmacol. 1999;14:139–51.
    1. Conradi HJ, Ormel J, de Jonge P. Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med. 2011;41:1165–74.
    1. McClintock SM, Husain MM, Wisniewski SR, et al. Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication. J Clin Psychopharmacol. 2011;31:180–6.
    1. Cleary M, Guy W. Factor analysis of the Hamilton Depression Scale. Drugs Exp Clin Res. 1975;1:115–20.
    1. Nutt D, Demyttenaere K, Janka Z, et al. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J Psychopharmacol. 2007;21:461–71.
    1. Bymaster FP, Beedle EE, Findlay J, et al. Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake. Bioorg Med Chem Lett. 2003;13:4477–80.
    1. Wong DT, Bymaster FP. Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype? Prog Drug Res. 2002;58:169–222.
    1. Karpa KD, Cavanaugh JE, Lakoski JM. Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002;8:361–76.
    1. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63:308–15.
    1. Goldstein DJ, Mallinckrodt C, Lu Y, Demitrack MA. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry. 2002;63:225–31.
    1. Nemeroff CB, Schatzberg AF, Goldstein DJ, et al. Duloxetine for the treatment of major depressive disorder. Psychopharmacol Bull. 2002;36:106–32.
    1. Shelton RC, Prakash A, Mallinckrodt CH, et al. Patterns of depressive symptom response in duloxetine-treated outpatients with mild, moderate or more severe depression. Int J Clin Pract. 2007;61:1337–48.
    1. Katz MM, Meyers AL, Prakash A, Gaynor PJ, Houston JP. Early symptom change prediction of remission in depression treatment. Psychopharmacol Bull. 2009;42:94–107.
    1. Brannan SK, Mallinckrodt CH, Brown EB, Wohlreich MM, Watkin JG, Schatzberg AF. Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. J Psychiatr Res. 2005;39:43–53.
    1. Detke MJ, Lu Y, Goldstein DJ, McNamara RK, Demitrack MA. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res. 2002;36:383–90.
    1. Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24:389–99.
    1. Nierenberg AA, Greist JH, Mallinckrodt CH, et al. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Curr Med Res Opin. 2007;23:401–16.
    1. Oakes TM, Myers AL, Marangell LB, et al. Assessment of depressive symptoms and functional outcomes in patients with major depressive disorder treated with duloxetine versus placebo: primary outcomes from two trials conducted under the same protocol. Hum Psychopharmacol. 2012;27:47–56.
    1. Perahia DG, Wang F, Mallinckrodt CH, Walker DJ, Detke MJ. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry. 2006;21:367–78.
    1. Pigott TA, Prakash A, Arnold LM, Aaronson ST, Mallinckrodt CH, Wohlreich MM. Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in patients with major depressive disorder. Curr Med Res Opin. 2007;23:1303–18.
    1. Robinson M, Oakes TM, Raskin J, Liu P, Shoemaker S, Nelson JC. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo. Am J Geriatr Psychiatry. 2014;22:34–45.
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.
    1. Stassen HH, Delini-Stula A, Angst J. Time course of improve ment under antidepressant treatment: a survival-analytical approach. Eur Neuropsychopharmacol. 1993;3:127–35.
    1. Morilak DA, Frazer A. Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders. Int J Neuropsychopharmacol. 2004;7:193–218.
    1. Singh AB, Bousman CA, Ng CH, Byron K, Berk M. Psychomotor depressive symptoms may differentially respond to venlafaxine. Int Clin Psychopharmacol. 2013;28:121–6.
    1. Papakostas GI, Nutt DJ, Hallett LA, Tucker VL, Krishen A, Fava M. Resolution of sleepiness and fatigue in major depressive disorder: a comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry. 2006;60:1350–5.
    1. Bialik RJ, Ravindran AV, Bakish D, Lapierre YD. A comparison of placebo responders and nonresponders in subgroups of depressive disorder. J Psychiatry Neurosci. 1995;20:265–70.
    1. Ball SG, Desaiah D, Zhang Q, Thase ME, Perahia DG. Efficacy and safety of duloxetine 60 mg once daily in major depressive disorder: a review with expert commentary. Drugs Context. 2013;3:212–45.
    1. Cowen PJ, Ogilvie AD, Gama J. Efficacy, safety and tolerability of duloxetine 60 mg once daily in major depression. Curr Med Res Opin. 2005;21:345–56.

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