Clinical Therapeutics/Volume 29, Theme Issue, 2007 Duloxetine for the Management of Diabetic Peripheral Neuropathic Pain: Evidence-Based Findings from Post Hoc Analysis of Three Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Studies Daniel K. Kajdasz, PhD1; Smriti lyengar, PhD1; Durisala Desaiah, PhD1; Misha-Miroslav Backonja, MD2;John T. Farrar, MD, MSCE, PhD3; David A. Fishbain, MD4; Troels S.Jensen, MDS; Michael C. Rowbotham, MD6; Christine N. Sang, MD, MPh7; Dan Ziegler, MD, MRCP, PhD, FRCPES; and HenryJ. McQuay, MD, FRCA, FRCP 9 1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana; 2University of Wisconsin, Madison, Wisconsin; 3Universityof Pennsylvania School of Medicine, Philadelphia, Pennsylvania; 4Miller School of Medicine, Universityof Miami, Miami, Florida; SArhus University, Danish Pain Research Center, Arkus, Denmark; 6Universityof California at San Francisco, San Francisco, California; 7Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 8German Diabetes Center, Leibniz Institute at the Heinrich Heine University, DOsseldorf Germany; and 9Churchill Hospital, Pain Relief Unit, Oxford, United Kingdom ABSTRACT Objective: This post hoc analysis was aimed to sum- marize the efficacy and tolerability of duloxetine as represented by number needed to treat (NNT) and number needed to harm (NNH) to provide a clinically useful assessment of the position of duloxetine among current agents used to treat diabetic peripheral neuro- pathic pain (DPNP). Methods: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo- controlled, parallel-group studies in which patients received 60 mg duloxetine either QD or BID or place- bo. NNT was calculated based on rates of response (defined as _>30% and _>50% reductions from baseline in the weekly mean of the 24-hour average pain severi- ty scores); NNH was calculated based on rates of dis- continuation due to adverse events (AEs). Results: Patients receiving duloxetine 60 mg QD and 60 mg BID had NNTs (95% CI) of 5.2 (3.8-8.3) and 4.9 (3.6-7.6), respectively, based on last observa- tion carried forward; NNTs of 5.3 (3.8-8.3) for 60 mg QD and 5.7 (4.1-9.7) for 60 mg BID were ob- tained based on baseline observations carried for- ward. The NNHs (95% CI) based on discontinuation due to AEs were 17.5 (10.2-58.8) in the duloxetine 60-mg QD group and 8.8 (6.3-14.7) in the 60-mg BID group. Conclusion: These post hoc results suggest that duloxetine was effective and well tolerated for the man- agement of DPNP and further support the importance of duloxetine as a treatment option for clinicians and patients to assist with the management of DPNP. (Clin Ther. 2007;29[Theme Issue]:2536-2546) Copyright © 2007 Excerpta Medica, Inc. Key words: duloxetine, NNT, NNH, neuropathy, diabetic peripheral neuropathic pain. INTRODUCTION The neurotransmitters serotonin (5-HT) and norepi- nephrine (NE) regulate pain signals in the central nervous system, including the spinal cord. 1 As the roles of 5-HT and NE in the modulation of pain per- ception have become better understood, dual 5-HT and serotonin NE reuptake inhibitors (SNRIs)-- including venlafaxine, milnacipran, and duloxetine-- have been assessed in terms of their therapeutic value as analgesics with more favorable tolerability pro- Acceptedfor publication September 19, 200 Z doi:l 0.1016/j.clinthera.2007.12.002 0149-2918/$32.00 Printed in the USA. Reproduction in whole or part is not permitted. Copyright © 2007 Excerpta Medica, Inc. 2536 Volume 29 Theme Issue