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Clinician Article

Topical NSAIDs for acute musculoskeletal pain in adults.



  • Derry S
  • Moore RA
  • Gaskell H
  • McIntyre M
  • Wiffen PJ
Cochrane Database Syst Rev. 2015 Jun 11;2015(6):CD007402. doi: 10.1002/14651858.CD007402.pub3. (Review)
PMID: 26068955
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Disciplines
  • Special Interest - Pain -- Physician
    Relevance - 7/7
    Newsworthiness - 6/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 7/7
    Newsworthiness - 3/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 7/7
    Newsworthiness - 3/7
  • Emergency Medicine
    Relevance - 6/7
    Newsworthiness - 6/7

Abstract

BACKGROUND: Use of topical NSAIDs to treat acute musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse events. This review is an update of 'Topical NSAIDs for acute pain in adults' originally published in Issue 6, 2010.

OBJECTIVES: To determine the efficacy and safety of topically applied NSAIDs in acute musculoskeletal pain in adults.

SEARCH METHODS: We searched the Cochrane Register of Studies Online, MEDLINE, and EMBASE to February 2015. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers websites. For the earlier review, we also searched our own in-house database and contacted manufacturers.

SELECTION CRITERIA: We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adults with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and extracted data. We used numbers of participants achieving each outcome to calculate the risk ratio and numbers needed to treat for an additional beneficial outcome (NNT) or additional harmful outcome (NNH) compared with placebo or other active treatment. We reported 95% confidence intervals (CI). We were particularly interested to compare different formulations (gel, cream, plaster) of individual NSAIDs.

MAIN RESULTS: For this update we added 14 new included studies (3489 participants), and excluded four studies. We also identified 20 additional reports of completed or ongoing studies that have not been published in full. The earlier review included 47 studies.This update included 61 studies. Most compared topical NSAIDs in the form of a gel, spray, or cream with a similar topical placebo; 5311 participants were treated with a topical NSAID, 3470 with placebo, and 220 with an oral NSAID. This was a 63% increase in the number of included participants over the previous version of this review. We also identified a number of studies in clinical trial registries with unavailable results amounting to about 5900 participants for efficacy and 5300 for adverse events.Formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and indomethacin demonstrated significantly higher rates of clinical success (more participants with at least 50% pain relief) than matching topical placebo (moderate or high quality data). Benzydamine did not. Three drug and formulation combinations had NNTs for clinical success below 4. For diclofenac, the Emulgel® formulation had the lowest NNT of 1.8 (95% CI 1.5 to 2.1) in two studies using at least 50% pain intensity reduction as the outcome. Diclofenac plasters other than Flector® also had a low NNT of 3.2 (2.6 to 4.2) based on good or excellent responses in some studies. Ketoprofen gel had an NNT of 2.5 (2.0 to 3.4), from five studies in the 1980s, some with less well defined outcomes. Ibuprofen gel had an NNT of 3.9 (2.7 to 6.7) from two studies with outcomes of marked improvement or complete remission. All other drug and formulation combinations had NNT values above 4, indicating lesser efficacy.There were insufficient data to compare reliably individual topical NSAIDs with each other or the same oral NSAID.Local skin reactions were generally mild and transient, and did not differ from placebo (high quality data). There were very few systemic adverse events (high quality data) or withdrawals due to adverse events (low quality data).

AUTHORS' CONCLUSIONS: Topical NSAIDs provided good levels of pain relief in acute conditions such as sprains, strains and overuse injuries, probably similar to that provided by oral NSAIDs. Gel formulations of diclofenac (as Emugel®), ibuprofen, and ketoprofen, and some diclofenac patches, provided the best effects. Adverse events were usually minimal.Since the last version of this review, the new included studies have provided additional information. In particular, information on topical diclofenac is greatly expanded. The present review supports the previous review in concluding that topical NSAIDs are effective in providing pain relief, and goes further to demonstrate that certain formulations, mainly gel formulations of diclofenac, ibuprofen, and ketoprofen, provide the best results. Large amounts of unpublished data have been identified, and this could influence results in updates of this review.


Clinical Comments

Emergency Medicine

Topical formulations of NSAIDs appear to be effective for acute musculoskeletal pain when compared to placebo. This treatment may be a useful alternative in patients who have contraindications to systemic NSAIDs. Future studies should compare topical versus oral NSAIDs in the treatment of acute musculoskeletal pain as it is not clear how these perform head to head. In addition, other factors such as cost should be considered in future studies and in clinical practice when prescribing topical NSAIDs.

Special Interest - Pain -- Physician

This is useful to pain specialists and emergency practitioners insofar as the review indicates that NSAIDS, which are non-addicting and have minimal street sales value, are consistently effective compared to placebo in alleviating pain from musculoskeletal origin. Unfortunately, most of the included trials involve placebo as the comparison and therefore do not inform choices between NSAIDS and other pharmacologic and non-pharmacologic modes of pain relief.

Special Interest - Pain -- Physician

This is a helpful review in that it confirms that: 1) topical NSAID are useful for pain relief; 2) more importantly, they have few side effects. While they are no better than oral medications, the side effect profile is critical.

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