Effectiveness and safety of topical versus oral nonsteroidal anti-inflammatory drugs: a comprehensive review

Phys Sportsmed. 2013 May;41(2):64-74. doi: 10.3810/psm.2013.05.2016.


Introduction: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) represent a relatively recent alternative to oral NSAIDs. Topical NSAIDs are designed to target their therapeutic effect locally to damaged tissue while minimizing systemic exposure. To better inform patients considering topical NSAIDs as an alternative to oral NSAIDs, this is the first comprehensive review to present all available evidence comparing topical NSAIDs with oral NSAIDs in the treatment of both acute and chronic musculoskeletal injury.

Methods: Six studies, including 600 subjects, compared the use of topical versus oral NSAIDs in the treatment of a variety of acute injuries. Nine trials, including 2403 subjects, studied topical versus oral NSAIDs for chronic injury treatment, almost exclusively for osteoarthritis (OA) of the knee. This review included all available comparative studies, the majority of which were well-designed, double-dummy, placebo-controlled trials. Relevant meta-analyses were also reviewed.

Results: Topical and oral NSAIDs performed statistically better than placebo for chronic injury treatment. Limited evidence comparing topical NSAIDs with placebo for acute injury treatment was available in the included studies, but supported greater effectiveness for topical NSAIDs. In all head-to-head comparisons, topical and oral NSAIDs demonstrated similar efficacy for treatment of both acute and chronic injuries. There were more gastrointestinal side effects in patients receiving oral NSAIDs, while local skin reactions occurred more frequently in patients treated with topical NSAIDs.

Conclusion: Overall, topical NSAIDs may be considered as comparable alternatives to oral NSAIDs and are associated with fewer serious adverse events (specifically GI reactions) when compared with oral NSAIDs. Caution should be exercised with the use of both topical and oral NSAIDs, including close adherence to dosing regimens and monitoring, particularly for patients with previous adverse reactions to NSAIDs.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Humans
  • Musculoskeletal Pain / drug therapy*


  • Anti-Inflammatory Agents, Non-Steroidal