Is duloxetine's effect on painful physical symptoms in depression an indirect result of improvement of depressive symptoms? Pooled analyses of three randomized controlled trials

Eiji Harada, Hirofumi Tokuoka, Shinji Fujikoshi, Jumpei Funai, Madelaine M. Wohlreich, Michael H. Ossipov, Nakao Iwata

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In treating Major Depressive Disorder with associated painful physical symptoms (PPS), the effect of duloxetine on PPS has been shown to decompose into a direct effect on PPS and an indirect effect on PPS via depressive symptoms (DS) improvement. To evaluate the changes in relative contributions of the direct and indirect effects over time, we analyzed pooled data from 3 randomized double-blind studies comparing duloxetine 60 mg/d with placebo in patients with major depressive disorder and PPS. Changes from baseline in Montgomery-Åsberg Depression Rating Scale total and Brief Pain Inventory-Short Form average pain score were assessed over 8 weeks. Path analysis examined the (1) direct effect of treatment on PPS and/or indirect effect on PPS via DS improvement and (2) direct effect of treatment on DS and/or indirect effect on DS via PPS improvement. At week 1, the direct effect of duloxetine on PPS (75.3%) was greater than the indirect effect through DS improvement (24.7%) but became less (22.6%) than the indirect effect (77.4%) by week 8. Initially, the direct effect of duloxetine on PPS was markedly greater than its indirect effect, whereas later the indirect effect predominated. Conversely, at week 1, the direct effect of treatment on DS (46.4%) was less than the indirect effect (53.6%), and by week 8 it superseded (62.6%) the indirect effect (37.4%). Thus, duloxetine would relieve PPS directly in the initial phase and indirectly via improving DS in the later phase.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalPain
Volume157
Issue number3
DOIs
Publication statusPublished - 01-03-2016

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Randomized Controlled Trials
Depression
Major Depressive Disorder
Pain
Duloxetine Hydrochloride
Double-Blind Method
Therapeutics
Placebos
Equipment and Supplies

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Harada, Eiji ; Tokuoka, Hirofumi ; Fujikoshi, Shinji ; Funai, Jumpei ; Wohlreich, Madelaine M. ; Ossipov, Michael H. ; Iwata, Nakao. / Is duloxetine's effect on painful physical symptoms in depression an indirect result of improvement of depressive symptoms? Pooled analyses of three randomized controlled trials. In: Pain. 2016 ; Vol. 157, No. 3. pp. 577-584.
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Is duloxetine's effect on painful physical symptoms in depression an indirect result of improvement of depressive symptoms? Pooled analyses of three randomized controlled trials. / Harada, Eiji; Tokuoka, Hirofumi; Fujikoshi, Shinji; Funai, Jumpei; Wohlreich, Madelaine M.; Ossipov, Michael H.; Iwata, Nakao.

In: Pain, Vol. 157, No. 3, 01.03.2016, p. 577-584.

Research output: Contribution to journalArticle

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