title: Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial.
abstract: OBJECTIVE
  There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy.
  
  
  OBJECTIVE
  To determine the effect of duloxetine, 60 mg daily, on average pain severity.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Stratified by chemotherapeutic drug and comorbid pain risk, patients were randomized to receive either duloxetine followed by placebo or placebo followed by duloxetine. Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after paclitaxel, other taxane, or oxaliplatin treatment.
  
  
  METHODS
  The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks.
  
  
  METHODS
  The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed using the Brief Pain Inventory-Short Form "average pain" item with 0 representing no pain and 10 representing as bad as can be imagined.
  
  
  RESULTS
  Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). The observed mean difference in the average pain score between duloxetine and placebo was 0.73 (95% CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38% of those initially receiving placebo reported decreased pain of any amount.
  
  
  CONCLUSIONS
  Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in pain.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00489411.
authors.affiliation: University of Michigan School of Nursing, Room 2151, Ann Arbor, MI 48109, USA. ellenls@umich.edu
authors.forename: Ellen M Lavoie
authors.initials: EM
authors.lastname: Smith
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Constance
authors.initials: C
authors.lastname: Cirrincione
authors.forename: Stewart
authors.initials: S
authors.lastname: Fleishman
authors.forename: Electra D
authors.initials: ED
authors.lastname: Paskett
authors.forename: Tim
authors.initials: T
authors.lastname: Ahles
authors.forename: Linda R
authors.initials: LR
authors.lastname: Bressler
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
authors.forename: Chetaye
authors.initials: C
authors.lastname: Knox
authors.forename: Nguyet
authors.initials: N
authors.lastname: Le-Lindqwister
authors.forename: Paul B
authors.initials: PB
authors.lastname: Gilman
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009437:Neuralgia / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D011788:Quality of Life; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes
references.citation: Arthritis Care Res (Hoboken). 2011 Jun;63(6):821-6
references.pmid: 21312349
references.citation: Cancer. 2008 Jun 15;112(12):2802-8
references.pmid: 18428211
references.citation: Eur J Oncol Nurs. 2010 Apr;14(2):101-10
references.pmid: 19897417
references.citation: J Clin Oncol. 2006 Feb 20;24(6):976-82
references.pmid: 16432077
references.citation: Pain. 2005 Jul;116(1-2):109-18
references.pmid: 15927394
references.citation: Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005454
references.pmid: 17943857
references.citation: Drug Metab Dispos. 2008 Dec;36(12):2484-91
references.pmid: 18809731
references.citation: Postgrad Med. 2012 Jul;124(4):145-53
references.pmid: 22913903
references.citation: Nurs Res. 2007 Sep-Oct;56(5):323-31
references.pmid: 17846553
references.citation: CNS Drugs. 2012 Jan 1;26(1):39-67
references.pmid: 22171584
references.citation: J Pain Symptom Manage. 2011 Dec;42(6):822-38
references.pmid: 21820851
references.citation: Clin J Pain. 2012 Oct;28(8):726-43
references.pmid: 22209797
references.citation: Pain. 2010 May;149(2):177-193
references.pmid: 20207481
references.citation: Pain Med. 2007 Jul-Aug;8(5):397-409
references.pmid: 17661853
references.citation: Int J Gynecol Cancer. 2003 Nov-Dec;13(6):741-8
references.pmid: 14675309
references.citation: J Peripher Nerv Syst. 2010 Dec;15(4):314-25
references.pmid: 21199103
references.citation: Muscle Nerve. 2011 Jun;43(6):910-7
references.pmid: 21484835
references.citation: Pain Med. 2005 Sep-Oct;6(5):346-56
references.pmid: 16266355
references.citation: Diabetes Care. 2011 Apr;34(4):818-22
references.pmid: 21355098
references.citation: Support Care Cancer. 2009 Aug;17(8):1071-80
references.pmid: 19089463
references.citation: Br J Clin Pharmacol. 2004 May;57(5):652-6
references.pmid: 15089819
references.citation: Lancet Neurol. 2012 Jun;11(6):521-34
references.pmid: 22608666
references.citation: Curr Med Res Opin. 2011 Dec;27(12):2361-72
references.pmid: 22017192
references.citation: J Pain. 2008 Feb;9(2):105-21
references.pmid: 18055266
references.citation: J Clin Oncol. 2011 Apr 10;29(11):1472-8
references.pmid: 21383290
references.citation: Oncol Nurs Forum. 2011 Mar;38(2):133-42
references.pmid: 21356652
references.citation: Ann Oncol. 1998 Jul;9(7):739-44
references.pmid: 9739440
references.citation: Spine (Phila Pa 1976). 2010 Jun 1;35(13):E578-85
references.pmid: 20461028
references.citation: Neurology. 2006 Oct 24;67(8):1411-20
references.pmid: 17060567
references.citation: J Peripher Nerv Syst. 2011 Sep;16(3):228-36
references.pmid: 22003937
references.citation: J Natl Cancer Inst. 2005 Jan 5;97(1):30-9
references.pmid: 15632378
references.citation: Continuum (Minneap Minn). 2012 Feb;18(1):60-84
references.pmid: 22810070
references.citation: Ann Acad Med Singap. 1994 Mar;23(2):129-38
references.pmid: 8080219
references.citation: Pain. 2009 Dec;146(3):253-260
references.pmid: 19625125
references.citation: Support Care Cancer. 2012 Jul;20(7):1491-7
references.pmid: 21814779
references.citation: Curr Drug Metab. 2011 Jul;12(6):570-7
references.pmid: 21395523
references.citation: J Clin Epidemiol. 2002 Mar;55(3):285-95
references.pmid: 11864800
references.citation: J Palliat Med. 2010 Nov;13(11):1389-91
references.pmid: 21091028
references.citation: Clin Ther. 2007;29 Suppl:2536-46
references.pmid: 18164920
references.citation: Pain Pract. 2011 Jan-Feb;11(1):33-41
references.pmid: 20602715
references.citation: J Natl Compr Canc Netw. 2009 Sep;7 Suppl 5:S1-S26; quiz S27-8
references.pmid: 19755042
references.citation: Cancer. 2007 Nov 1;110(9):2110-8
references.pmid: 17853395
references.citation: Support Care Cancer. 2012 Dec;20(12):3355-64
references.pmid: 22584733
references.citation: Pain Med. 2006 Sep-Oct;7(5):373-85
references.pmid: 17014595
references.citation: Support Care Cancer. 2011 Jun;19(6):833-41
references.pmid: 20496177
references.citation: Expert Opin Drug Saf. 2010 Jul;9(4):525-37
references.pmid: 20465525
references.citation: J Pain. 2004 Mar;5(2):133-7
references.pmid: 15042521
references.citation: Pain. 2008 Jun;136(3):432-444
references.pmid: 18395345
references.citation: Pain. 2002 Jul;98(1-2):195-203
references.pmid: 12098632
references.citation: Pain. 2001 Nov;94(2):149-158
references.pmid: 11690728
references.citation: J Clin Neurophysiol. 1997 Jan;14(1):2-31
references.pmid: 9013357
references.citation: J Pain Symptom Manage. 2002 Dec;24(6):547-61
references.pmid: 12551804
references.citation: Clin Pharmacol Ther. 2003 Mar;73(3):170-7
references.pmid: 12621382
references.citation: Med Care. 2003 May;41(5):582-92
references.pmid: 12719681
references.citation: Pain. 2009 Dec;146(3):238-244
references.pmid: 19836888
references.citation: Pain. 2011 Jan;152(1):31-37
references.pmid: 20598442
references.citation: Eur J Cancer. 2010 Feb;46(3):479-94
references.pmid: 20045310
references.citation: Cancer Nurs. 2010 May-Jun;33(3):173-83
references.pmid: 20357656
references.citation: Support Care Cancer. 2011 Dec;19(12):1991-6
references.pmid: 21080201
references.citation: Anticancer Res. 2009 Jul;29(7):2601-6
references.pmid: 19596934
references.citation: Crit Rev Oncol Hematol. 2012 Apr;82(1):51-77
references.pmid: 21908200
references.citation: J Clin Psychopharmacol. 2007 Feb;27(1):28-34
references.pmid: 17224709
references.citation: JAMA. 2006 Apr 5;295(13):1517-8
references.pmid: 16595756
references.citation: Int J Gynecol Cancer. 2007 Mar-Apr;17(2):387-93
references.pmid: 17362317
references.citation: Pain Med. 2010 Mar;11(3):337-46
references.pmid: 20030743