Clinician Article

Topical NSAIDs for chronic musculoskeletal pain in adults.

  • Derry S
  • Conaghan P
  • Da Silva JA
  • Wiffen PJ
  • Moore RA
Cochrane Database Syst Rev. 2016 Apr 22;4:CD007400. doi: 10.1002/14651858.CD007400.pub3. (Review)
PMID: 27103611
Read abstract Read evidence summary Read full text
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Rheumatology
    Relevance - 6/7
    Newsworthiness - 4/7
  • Physical Medicine and Rehabilitation
    Relevance - 5/7
    Newsworthiness - 4/7
  • Special Interest - Pain -- Physician
    Relevance - 5/7
    Newsworthiness - 4/7


BACKGROUND: Use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) to treat chronic 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 chronic musculoskeletal pain in adults', originally published in Issue 9, 2012.

OBJECTIVES: To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs for chronic musculoskeletal pain in adults.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and our own in-house database; the date of the last search was February 2016. We also searched the references lists of included studies and reviews, and sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' web sites.

SELECTION CRITERIA: We included randomised, double-blind, active or inert carrier (placebo) controlled trials in which treatments were administered to adults with chronic musculoskeletal pain of moderate or severe intensity. Studies had to meet stringent quality criteria and 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 risk ratio and numbers needed to treat (NNT) or harm (NNH) compared to carrier or other active treatment. We were particularly interested to compare different formulations (gel, cream, plaster) of individual NSAIDs. The primary outcome was 'clinical success', defined as at least a 50% reduction in pain, or an equivalent measure such as a 'very good' or 'excellent' global assessment of treatment, or 'none' or 'slight' pain on rest or movement, measured on a categorical scale.

MAIN RESULTS: We identified five new studies for this update, which now has information from 10,631 participants in 39 studies, a 38% increase in participants from the earlier review; 33 studies compared a topical NSAID with carrier. All studies examined topical NSAIDs for treatment of osteoarthritis, and for pooled analyses studies were generally of moderate or high methodological quality, although we considered some at risk of bias from short duration and small size.In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2343 participants) was 9.8 (95% confidence interval (CI) 7.1 to 16) (moderate quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2573 participants) was 6.9 (5.4 to 9.3) (moderate quality evidence). There was too little information for analysis of other individual topical NSAIDs compared with carrier. Few trials compared a topical NSAID to an oral NSAID, but overall they showed similar efficacy (low quality evidence). These efficacy results were almost completely derived from people with knee osteoarthritis.There was an increase in local adverse events (mostly mild skin reactions) with topical diclofenac compared with carrier or oral NSAIDs, but no increase with topical ketoprofen (moderate quality evidence). Reporting of systemic adverse events (such as gastrointestinal upsets) was poor, but where reported there was no difference between topical NSAID and carrier (very low quality evidence). Serious adverse events were infrequent and not different between topical NSAID and carrier (very low quality evidence).Clinical success with carrier occurred commonly - in around half the participants in studies lasting 6 to 12 weeks. Both direct and indirect comparison of clinical success with oral placebo indicates that response rates with carrier (topical placebo) are about twice those seen with oral placebo.A substantial amount of data from completed, unpublished studies was unavailable (up to 6000 participants). To the best of our knowledge, much of this probably relates to formulations that have never been marketed.

AUTHORS' CONCLUSIONS: Topical diclofenac and topical ketoprofen can provide good levels of pain relief beyond carrier in osteoarthritis for a minority of people, but there is no evidence for other chronic painful conditions. There is emerging evidence that at least some of the substantial placebo effects seen in longer duration studies derive from effects imparted by the NSAID carrier itself, and that NSAIDs add to that.

Clinical Comments

Family Medicine (FM)/General Practice (GP)

Useful Cochrane review that confirms clinical perception that topical NSAIDs help some people and seem to be safe, although the safety data could be better reported. Given limited effects and concerns of harm or side effects with most of the oral options we have, and the concerns with polypharmacy in older patients, I will keep suggesting topical NSAIDs to many of my patients.

Family Medicine (FM)/General Practice (GP)

More data to support the effectiveness of 2 topical NSAIDs for OA of the knee (mainly). I should probably prescribe this safer-than-oral alternative more often. (But I do wonder how it could work.)

General Internal Medicine-Primary Care(US)

This Cochrane review reinforces the small marginal value of topical capsaicin and diclofenac to help relieve musculoskeletal pain (i.e., 6/10 patients express relief with these agents versus 5/10 patients express relief with a carrier agent) after 6-12 weeks. I expect most physicians already know this information. The publication will not change my practice.

General Internal Medicine-Primary Care(US)

Topical NSAIDs for chronic pain are always an option for individuals who are intolerant of or have a contraindication for oral NSAIDs. This study demonstrates similar efficacy between topical and oral NSAIDs, and supports their use as an alternative for chronic pain management. For many older persons with osteoarthritis, this is a viable option.

Special Interest - Pain -- Physician

Very informative and useful review.

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