title: Efficacy and Safety of Duloxetine on Osteoarthritis Knee Pain: A Meta-Analysis of Randomized Controlled Trials.
abstract: OBJECTIVE
  The aim of this meta-analysis was to evaluate the efficacy and safety of duloxetine for management of osteoarthritis knee (OAK) pain.
  
  
  METHODS
  A systematic literature search of articles for management of OAK using duloxetine were performed in PubMed, EBSCO, EMBASE, ScienceDirect, MEDLINE, ClinicalTrials.gov, Google Scholar, and Cochrane Central Register of Controlled Trials from the available date of inception until the latest issue (October 2013). Potentially relevant randomized controlled trials (RCTs) regarding to comparison of efficacy and safety of duloxetine with placebo for managing OAK pain were included. Also, studies with specific data regarding to pain reductions and response rate, Patient Global Impression of Improvement (PGI-I), functional improvement, Western Ontario and McMaster Osteoarthritis Index (WOMAC), adverse events (AEs), treatment-emergent AEs (TEAEs), mortality were included and analyzed, and those with confounding conditions were excluded. Studies were assessed for quality using the Jadad five-point score for RCTs. Finally, a meta-analysis of all RCTs eligible for inclusion criteria was performed using Review Manager 5.1 meta-analysis software.
  
  
  RESULTS
  Three RCTs that enrolled 1,011 patients were included in our meta-analysis. There were statistically significant differences between patients taking duloxetine and those taking placebo with regard to the reductions in pain intensity (992 patients, mean difference [MD] = -0.88, 95% confidence interval [CI] -1.11--0.65, P < 0.0001), a moderate improvement in pain intensity (>= 30% response rate; 989 patients, risk ratio [RR] = 1.49, 95% CI 1.31-1.70, P < 0.0001), a substantial improvement in pain intensity (>=50% response rate; 989 patients, RR = 1.69, 95% CI 1.27-2.25, P = 0.0004). Statistically significant differences in PGI-I (976 patients, MD = -0.47, 95% CI -0.63 to -0.30, P < 0.0001) and WOMAC-physical function subscale (977 patients, MD = -4.25, 95% CI -5.82 to -2.68, P < 0.0001) were observed. Similarly, more AEs, TEAEs, and discontinuations for any reason were associated with the use of duloxetine than with placebo (1,011 patients, RR = 2.15, 95% CI 1.48-3.11, P < 0.0001; 1,011 patients, RR = 1.32, 95% CI 1.16-1.49, P < 0.0001; 1,011 patients, RR = 1.43, 95% CI 1.14-1.78, P = 0.002, respectively). However, differences in serious AEs were not significantly statistically different. Moreover, no deaths occurred during these three studies.
  
  
  CONCLUSIONS
  This analysis suggests duloxetine (60/120 mg quaque die (QD)), compared with placebo control, resulted in a greater reduction in pain, improved function and patient-rated impression of improvement, and acceptable adverse effects for the treatment of OAK pain after approximately 10-13 weeks of treatment.
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
authors.forename: Zhao Yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
authors.forename: Sheng Ying
authors.initials: SY
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
authors.forename: Shu Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Yue Bei People's Hospital, Shantou University, Shaoguan, 512026, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
authors.forename: Hai Zhen
authors.initials: HZ
authors.lastname: Lin
authors.affiliation: Pharmaceutical Research & Development, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
authors.forename: Jing Ming
authors.initials: JM
authors.lastname: Lin
mesh_terms: D000700:Analgesics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007719:Knee Joint / Q000187:drug effects* / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000068736:Duloxetine Hydrochloride
keywords: Duloxetine; Meta-Analysis; Osteoarthritis Knee Pain; Randomized Controlled Trials