title: 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.
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at week 1, the direct effect of treatment on DS (46.4%) was less than the indirect effect (53.6%), and by week 8 it superseded (62.6%) the indirect effect (37.4%).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.
authors.affiliation: Medical Science, Eli Lilly Japan K.K., Kobe, Hyogo, Japan Statistical Science, Eli Lilly Japan K.K., Kobe, Hyogo, Japan Science Communications, Eli Lilly Japan K.K., Kobe, Hyogo, Japan Global Neuroscience, Eli Lilly and Company, Indianapolis, IN, USA inVentiv Health Clinical, LLC, Ann Arbor, MI, USA Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tokuoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujikoshi
authors.forename: Jumpei
authors.initials: J
authors.lastname: Funai
authors.forename: Madelaine M
authors.initials: MM
authors.lastname: Wohlreich
authors.forename: Michael H
authors.initials: MH
authors.lastname: Ossipov
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000700:Analgesics / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D010146:Pain / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D010147:Pain Measurement / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents; D000068736:Duloxetine Hydrochloride