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Assessment of direct analgesic effect of duloxetine for chronic low back pain: post hoc path analysis of double-blind, placebo-controlled studies

Authors Enomoto H, Fujikoshi S, Funai J, Sasaki N, Ossipov MH, Tsuji T, Alev L, Ushida T

Received 30 January 2017

Accepted for publication 26 April 2017

Published 1 June 2017 Volume 2017:10 Pages 1357—1368


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Michael Schatman

Hiroyuki Enomoto,1 Shinji Fujikoshi,2 Jumpei Funai,3 Nao Sasaki,4 Michael H Ossipov,5 Toshinaga Tsuji,6 Levent Alev,7 Takahiro Ushida8

1Medical Science, Eli Lilly Japan K.K., Tokyo, 2Statistical Science, 3Science Communications, 4Medical Science, Eli Lilly Japan K.K., Kobe, Japan; 5Clinical Division, inVentiv Health, LLC, Blue Bell, PA, USA; 6Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan; 7Medical Department, Lilly Turkey, Istanbul, Turkey; 8Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, Japan

Background: Comorbid depression and depressive symptoms are common in patients with chronic low back pain (CLBP). Duloxetine is clinically effective in major depressive disorder and several chronic pain states, including CLBP. The objective of this post hoc meta-analysis was to assess direct and indirect analgesic efficacy of duloxetine for patients with CLBP in previous clinical trials.
Methods: Post hoc path analyses were conducted of 3 randomized, double-blind, clinical studies of patients receiving duloxetine or placebo for CLBP. The primary outcome measure for pain was the Brief Pain Inventory, average pain score. A secondary outcome measure, the Beck Depression Inventory-II, was used for depressive symptoms. The changes in score from baseline to endpoint were determined for each index. Path analyses were employed to calculate the proportion of analgesia that may be attributed to a direct effect of duloxetine on pain.
Results: A total of 851 patients (400 duloxetine and 451 placebo) were included in this analysis. Duloxetine significantly improved pain scores compared with placebo (p<0.001). It also significantly improved depressive scores compared with placebo (p=0.015). Path analyses showed that 91.1% of the analgesic effect of duloxetine could be attributed to a direct analgesic effect, and 8.9% to its antidepressant effect. Similar results were obtained when data were evaluated at weeks 4 and 7, and when patients were randomized to subgroups based on baseline pain scores, baseline depressive symptoms scores, and gender.
Conclusion: Duloxetine significantly improved pain in patients with CLBP. Path analyses results suggest that duloxetine produced analgesia mainly through mechanisms directly impacting pain modulation rather than lifting depressive symptoms. This effect was consistent across all subgroups tested.

Keywords: duloxetine, direct analgesic effect, chronic low back pain, post hoc path analysis, double-blind, placebo-controlled studies

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