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#40 Topical NSAIDs: Do they top Placebo or Oral NSAIDs?

Are topical non-steroidal anti-inflammatories (NSAIDs) effective in reducing pain in acute and chronic (including osteoarthritis) musculoskeletal pain?

In acute and chronic (like osteoarthritis) musculoskeletal pain, topical NSAIDs are superior to placebo and equivalent to oral NSAIDs. Topical NSAIDs adverse event rates are not statistically greater than placebo.

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Acute musculoskeletal pain: Systematic review of 47 randomized controlled trials (RCTs) with 5,512 patients (within 24-48 hours onset).1 
  • Clinical success (defined as 50% pain reduction, good pain relief, or equivalent): Statistically significantly greater with topical NSAID vs. placebo, relative benefit 1.5 [Confidence Interval (CI) 1.4-1.6] 
    • Topical NSAID 65% vs. placebo 43%, Number Needed to Treat (NNT)=5.  
  • Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were all effective. 
  • Adverse events and withdrawals were not different. 
  • Benefit decreased over time: 6-8 days NNT=4 and 9-14 days NNT=10. 
    • This may be due to recovery over time in the placebo arm.   
Chronic musculoskeletal pain (including osteoarthritis): Four systematic reviews comparing topical NSAIDs to placebo.2-5  
  • Short-term (two weeks) effects: Consistent statistically significant improvement.2,3 Example, relative benefit 1.9 (CI 1.7-2.2), NNT=5 for improved pain over placebo.3   
  • Long-term (=12 weeks) effects: Statistically significant pain reduction vs. placebo, NNT=11.5 
  • Comparing topical to oral NSAIDs: Pain control is similar (relative risk 1.1, CI 0.9-1.3).3,5  Overall withdrawals for adverse effects is also similar.5  
  • Other meta-analyses6,7 support topical NSAIDs in acute musculoskeletal pain or single joint osteoarthritis.  
    • Present evidence does not support topical NSAIDs in back pain, neuropathic conditions or widespread pain.7  
  • UK osteoarthritis guidelines place topical NSAIDs (or acetaminophen) as first line pharmacotherapy for knee and/or hand osteoarthritis.8 
    • Intra-articular NSAID levels are therapeutic with topical or oral but circulation levels of topical NSAIDs are 15% of oral NSAIDs.8 
  • Recommending specific formulations is challenged by the lack of trials comparing different formulations (types of gels/creams) on clinical outcomes. 

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1. Massey T, Derry S, Moore AR, et al. Cochrane Database System Rev. 2014; 6:CD007402.

2. Lin J, Zhang W, Jones A, et al. BMJ. 2004; 329:324.

3. Mason L, Moore RA, Edwards JE, et al. BMC Musculoskeletal Disorders. 2004; 5:28.

4. Biswal S, Medhi B, Pandhi P. J Rheumatol. 2006; 33:1841-4.

5. Derry S, Moore RA, Rabbie R. Cochrane Database System Rev. 2012; 9:CD007400.

6. Bandolier. Topical NSAIDs. 2003 April. Available at: Accessed February 12, 2015.

7. Haroutiunian S, Drennan DA, Lipman AG. Pain Medicine. 2010; 11:535-49.

8. National Institute for Health and Care Excellence. Osteoarthritis Care and Management in Adults (clinical guidelines CG177). February 2014. Available at: Accessed February 12, 2015.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 10/02/2015

By: Adrienne J Lindblad BSP ACPR PharmD


Evidence Updated: Systematic review added; Bottom Line: Unchanged.

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