title: Duloxetine Compared with Pregabalin for Diabetic Peripheral Neuropathic Pain Management in Patients with Suboptimal Pain Response to Gabapentin and Treated with or without Antidepressants: A Post Hoc Analysis.
abstract: OBJECTIVE
  To examine the efficacy of duloxetine vs. pregabalin in the treatment for diabetic peripheral neuropathic pain (DPNP), comparing patient subgroups with and without concomitant antidepressant use.
  
  
  METHODS
  This post hoc analysis assessed data from a randomized 12-week study that confirmed the noninferiority of duloxetine to pregabalin. In the previously published study, patients with DPNP with inadequate response to gabapentin were switched to duloxetine monotherapy, combination therapy of duloxetine plus gabapentin, or pregabalin monotherapy. Current, stable antidepressant use was allowed; 79 patients were concomitantly treated with antidepressants and 328 without antidepressants. In this post hoc analysis, improvement in the weekly mean of diary-based average daily pain ratings (numerical rating scale: 0-10) in antidepressant users and nonusers was analyzed using a longitudinal mixed-models repeated-measures (MMRM) analysis, including a test of the 3-way interaction (antidepressant subgroup by treatment by week) to assess whether the differences among treatment groups over 12 weeks differ between the antidepressant-use subgroups.
  
  
  RESULTS
  The 3-way interaction was significant (P = 0.035), demonstrating that treatment-group differences in pain reduction over time differ between the subgroups. Among patients without antidepressant use, patients treated with duloxetine had significantly greater pain reduction than pregabalin at Week 4 and at each successive week up to the 12-week endpoint (-2.8 for duloxetine and -2.1 for pregabalin; P = 0.031); patients treated with duloxetine plus gabapentin had greater pain reduction than pregabalin at Weeks 2, 3, 5, and 7 to 9 (P ≤ 0.05) but not at endpoint (-2.4; P = 0.222). Among concomitant antidepressant users, no treatment-group differences were found.
  
  
  CONCLUSIONS
  In patients with DPNP inadequately treated with gabapentin without the concomitant use of antidepressants, switching to duloxetine instead of pregabalin may provide better pain reduction. Conversely, in nonresponders to gabapentin who are concomitantly using an antidepressant, switching to duloxetine or pregabalin may provide similar pain reductions.
authors.affiliation: Division of Endocrinology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, U.S.A.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tanenberg
authors.affiliation: Lilly USA, LLC, Indianapolis, Indiana, U.S.A.
authors.forename: David B
authors.initials: DB
authors.lastname: Clemow
authors.affiliation: INC Research, Raleigh, North Carolina, U.S.A.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Giaconia
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, U.S.A.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Risser
mesh_terms: D000328:Adult; D000368:Aged; D000588:Amines / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage; D000928:Antidepressive Agents / Q000008:administration & dosage*; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage*; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D000069583:Pregabalin / Q000008:administration & dosage*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D000588:Amines; D000700:Analgesics; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000068736:Duloxetine Hydrochloride
keywords: diabetic neuropathy; painful; therapeutics