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#269 Osteoarthritis pain getting you down? Duloxetine  


CLINICAL QUESTION
Do Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), specifically duloxetine, improve pain in patients with osteoarthritis? 

BOTTOM LINE
Duloxetine can meaningfully reduce osteoarthritis pain scores (by at least 30%) for ~60% of patients compared to ~40% on placebo. An average pain of ~6 (scale 0-10) will be reduced by ~2.5 points, compared to 1.7 on placebo. Duloxetine adverse effects lead to withdrawal in 12% of patients versus 6% on placebo.  


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EVIDENCE
Six systematic reviews with 2-7 randomized controlled trials (RCTs) and 487-2102 patients.1-6 Duloxetine 60-120mg daily versus placebo, results statistically significant unless indicated. 
  • Proportion of patients attaining a meaningful pain reduction (generally ≥30% reduction in pain score): 
    • Systematic review (6 RCTs, 2060 patients)1 of hip or knee osteoarthritis, over 10-18 weeks: 64% taking duloxetine versus 43% taking placebo, number needed to treat (NNT)=5. 
    • Other systematic reviews found similar:3,5-6 NNT=6-9. 
    • One RCT (231 patients) randomized patients to 60mg or 120mg and found no difference.7 
  • Improvement in baseline pain scores (0-10 point scale, lower scores indicate less pain): 
    • Systematic review (5 RCTs, 2059 patients),5 patients started with an average score of 5.8: duloxetine improved pain 0.8 more than placebo, achieving a mean pain score of 3.3 versus 4.1 for placebo which is likely clinically meaningful. 
    • Another systematic review found similar.3 
  • Adverse events: 
    • Overall adverse events:4 55% versus 37% (placebo), number needed to harm (NNH)=6. 
      • Most common adverse events:4 gastrointestinal 36% versus 8% (placebo), (NNH=4). 
        • Specifically6 nausea (NNH 16), fatigue (NNH 17), constipation (NNH 19), erectile dysfunction (NNH 20), abdominal pain (NNH 34). 
    • Withdrawal due to adverse events:4 12% versus 6% (placebo), NNH=17. 
    • Other systematic reviews found similar.1-6 
    • Limitations: all industry-funded studies. 
Context: 
  • No RCTs looked at venlafaxine to treat osteoarthritis pain. 
  • Duloxetine is “conditionally recommended” by the Osteoarthritis Research Society International guidelines and by the American College of Rheumatology, however, tolerability needs to be considered.8-9 
  • A PEER Simplified Decision Aid on osteoarthritis can assist with patient informed decision making and is available online.10 
July 13, 2020

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Author(s):

  • Betsy Thomas BSc. Pharm
  • G. Michael Allan MD CCFP
  • Joey Ton PharmD

1. Ton J, Perry D, Thomas B, et al. Can Fam Physician. 2020 Mar; 66(3):e89-e98.

2. Moore RA, Cai N, Skljarevski V, Tölle TR. Eur J Pain. 2014 Jan; 18(1):67-75.

3. Wang ZY, Shi SY, Li SJ, et al. Pain Med. 2015 Jul; 16(7):1373-85.

4. Osani MC, Bannuru RR. Korean J Intern Med. 2019 Sep; 34(5):966-973.

5. Gao SH, Huo JB, Pan QM, et al. Medicine (Baltimore). 2019 Nov; 98(44):e17541.

6. Citrome L, Weiss-Citrome A. Postgrad Med. 2012 Jan; 124(1):83-93.

7. Chappell A, Ossanna M, Liu-Seifert H, et al. Pain. 2009 Dec; 146(3):253-60.

8. Bannuru RR, Osani MC, Vaysbrot EE, et al. Osteoarthritis Cartilage. 2019 Nov; 27(11):1578-1589.

9. Kolasinski S, Neogi T, Hochberg MC, et al. Arthritis Rheumatol. 2020 Feb; 72(2):220-233.

10. Lindblad AJ, McCormack J, Korownyk CS, et al. Can Fam Physician. 2020 Mar; 66(3):191-193. Available at: https://www.cfp.ca/content/66/3/191 Accessed 08-APR-2020.

Authors do not have any conflicts of interest to declare.