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

Abstract

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

Acknowledgments

The authors thank Noelle Gasco, full-time employee of inVentiv Health Clinical, LLC, for editorial support. These trials and the preparation of the manuscript were sponsored by Eli Lilly and Company, Indianapolis, IN, USA. Eli Lilly and Company contracted inVentiv Health Clinical for writing and editorial support.

Disclosure

HE, SF, JF, NS, and LA are full-time employees of Eli Lilly Japan K.K. TT is a full-time employee and minor stock holder of Shionogi & Co. Ltd. TU has received honoraria from Hisamitsu, Pfizer, Shionogi, Lilly, and Daiichi-Sankyo and grant/research funding from Seikagaku Corporation, Nihon Zoki, Astellas, Pfizer, Eisai, Daiichi-Sankyo, Medtronic, and Kyowa-Hakko Kirin. MHO is a full-time employee of inVentiv Health Clinical, LLC. The authors report no other conflicts of interest in this work.