Background (Information Similar to Relevance for Nursing)
Chronic musculoskeletal pain (CMP), pain lasting greater than 3 months or past the time of normal tissue healing, is a prevalent condition and a major cause of disability and absence from work worldwide (Centers for Disease Control and Prevention, 2016; Santos, Alarcao, Fareleira, Vaz-Carneiro, & Costa, 2015; Wall, 2016). Oftentimes, topical nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed to treat chronic musculoskeletal conditions with the anticipation that they will relieve a patient's pain and inflammation while minimizing the side effects experienced if prescribed by other routes, achieving a balance of efficacy and safety. This has not been without controversy in analgesic practice (Derry, Conaghan, Da Silva, Wiffen, & Moore, 2016).
NSAIDs are commonly prescribed as a first-line therapy, as a nonopioid analgesic, for people with substance use disorders, the elderly, as well as to reduce gastrointestinal adverse events commonly experienced with oral administration. (AAPM, 2009; Derry, Moore, Gaskell, McIntyre, & Wiffen, 2015; Savage, Kirsh, & Passik, 2008). How effective is this form of pharmacological management? Topical NSAIDs are produced for application on a superficial localized site and may not be indicated for deep visceral pain or deep-seated join pain. Are our patient's pain management needs being met when topical NSAIDs are prescribed for CMP? Join me in this commentary, as we examine the efficacy of commonly prescribed topical NSAIDs for the treatment of CMP by way of summarizing Derry et al.'s (2016) review of "Topical NSAIDs for Chronic Musculoskeletal Pain in Adults." Let's see what the evidence says.
Objective/s (Information Similar to Review Question)
Derry et al. (2016) aimed to review the evidence from randomized, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs for CMP in adults. This is an update to the author's original review of 2012.
Intervention/Methods (Information Similar to Study Characteristics)
The authors searched various electronic databases, trial registers, and reference lists to locate randomized, controlled, double-blinded trials. Studies were included if they had a minimum of 10 participants per treatment type, participants were 16 years or older with CMP of moderate or severe intensity for at least 3 months, the study lasted a minimum of 2 weeks, topical NSAID was a treatment arm and a placebo alone or an active analgesic intervention was another, and the topical NSAID was applied at least once a day. Studies were excluded if they were published only as short conference abstracts, studied experimentally induced pain, or investigated salicylates as the active treatment option (no longer considered topical NSAIDs).
A hierarchy of outcomes was used, based on participant-reported improvement-not physician or investigator report of efficacy-to find the primary outcome of clinical success. Clinical success was defined as no less than a 50% reduction in pain or equivalent on a categorical scale. Evidence-based tools were utilized to ensure rigor, minimize bias, and rate the quality of evidence, including the use of two review authors, standardized data extraction forms, various Cochrane tools, protocols, and best practices for conducting systemic reviews.
Results
The authors identified five new studies for inclusion, yielding a 38% increase in study participants from 7,688 to 10,631 in 39 studies (Figure 1). All studies examined topical NSAIDs for treatment of osteoarthritis, and for pooled analyses studies were generally of moderate or high methodological quality. The authors did note some risk of bias from short duration and small size.
Primary results were as follows: In studies lasting 6-12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than placebo carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2,343 participants) was 9.8 (95% confidence interval [CI] [7.1, 16]) (moderate-quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2,573 participants) was 6.9 (95% CI [5.4, 9.3]) (moderate-quality evidence). Moderate-quality evidence means that further research may change our estimate of the effect, and very low-quality evidence means the authors were very uncertain about the accuracy of our estimate.
Skin reactions (mostly mild) were more common with topical diclofenac than topical placebo; there was no difference between topical ketoprofen and topical placebo (moderate-quality evidence). Other adverse events, such as stomach upsets, were poorly reported in these studies but were no different between topical diclofenac or ketoprofen and topical placebo (very low-quality evidence). Serious adverse events were uncommon.
Conclusions
The results of this review were in substantial agreement with the author's original review, as well as other current systemic reviews of similar nature. The quality of evidence for topical diclofenac and topical ketoprofen compared with placebo was moderate for efficacy and very low for harmful effects. Topical diclofenac and topical ketoprofen can provide good levels of pain relief in knee osteoarthritis in people older than 40 years but only in about 10% more people than with placebo. These topical NSAIDs should be considered for the treatment of CMP associated with knee osteoarthritis. Adverse events were minimal with topical NSAIDs. Based on these findings, there is little good evidence that supports the use of topical NSAIDs on conditions outside of osteoarthritis. Further studies are required on topical NSAIDs' efficacy in conditions other than osteoarthritis and on those that compare the benefits and harms of topical and oral formulations.
Implications for Practice
Earlier studies and reviews provided good evidence for the efficacy of topical NSAIDs in acute and chronic musculoskeletal pain. Evidence is like time; as we learn and inquire more, it changes. Studies and reviews that examine statistical significance and clinical efficacy are important. Derry et al.'s (2016) review is applicable to practice, as there was little evidence to support the use of diclofenac or ketoprofen for CMP outside of chronic knee osteoarthritis. A minority of patient's reported good levels of pain relief.
CMP has clinical, psychological, and social implications that limit complex activities, contributes to lost work productivity, reduces quality of life, and carries stigma. Treatment of chronic pain continues to be challenging and controversial. Patients with a history of past or active substance use, the elderly, or those whose risk of harm is greater than the proposed benefit may be prescribed topical NSAIDs, such as diclofenac or ketoprofen, as first-line or concomitant pain management therapy. After reviewing the evidence, we see this may not be effective. Keeping in mind that patient response to medication varies; using this evidence, nurses can better advocate for patients when these medications are prescribed for conditions other than chronic knee osteoarthritis as first-line therapy or when patients deny relief of CMP. The findings, when implemented, provide for safer quality patient-centered care with individualized treatment plans and plans of care.
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