Topical non-steroidal anti-inflammatory drug use for pediatric acute musculoskeletal pain: a scoping review.

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Topical non-steroidal anti-inflammatory drugs (NSAIDs) effectively treat acute musculoskeletal pain in adults, but evidence in children is limited. This scoping review aims to summarize current evidence for use in children and identify literature gaps to inform future research. We conducted a scoping review following Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews guidelines. Our electronic search included published studies across six databases, grey literature, and unpublished or ongoing trials. Studies involving children (< 18years) with acute musculoskeletal pain treated with topical NSAIDs in Emergency Department (ED), urgent care, or ambulatory settings were included. We extracted data on study methodology, participant characteristics, clinical outcomes, adverse events, and rescue analgesia use. We performed critical appraisal using Joanna Briggs Institute tools. Three studies met inclusion criteria: two randomized-controlled trials and one non-randomized trial, totaling 467 participants aged 6-18years. Interventions included ketoprofen gel, methyl salicylate/1-menthol patch, and diclofenac epolamine patch for ankle sprains or minor soft tissue injuries. Treatment durations ranged from 30minutes to 14days. Studies varied in design, intervention protocols, outcome measures, and reporting quality. Common outcomes included pain reduction, rescue medication use, and adverse events. Overall, findings suggest topical NSAIDs may be effective and well tolerated for managing acute musculoskeletal pain in children. However, the available evidence has low credibility with high risk of bias and methodological heterogeneity. No studies compared topical with oral NSAIDs, and few assessed long-term safety, functional recovery, or participant-centered outcomes such as satisfaction or adherence. Topical NSAIDs may be a potential option for relief of acute musculoskeletal pain in children, although evidence is grossly limited. High-quality randomized-controlled trials are needed to evaluate the efficacy and safety of topical NSAIDs in children before recommendations for use in clinical practice can be made.

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  • Research Article
  • Cite Count Icon 111
  • 10.1002/14651858.cd003686.pub2
Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults.
  • May 31, 2013
  • The Cochrane database of systematic reviews
  • Porjai Pattanittum + 3 more

Lateral elbow pain, or tennis elbow, is a common condition that causes pain in the elbow and forearm. Although self-limiting, it can be associated with significant disability and often results in work absence. It is often treated with topical and oral non-steroidal anti-inflammatory drugs (NSAIDs). This is an update of a review first published in 2002 (search date October 11, 2012). To assess the benefits and harms of topical and oral NSAIDs for treating people with lateral elbow pain. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE and SciSearch up to October 11, 2012. No language restriction was applied. Studies were included if they were randomised or quasi-randomised controlled trials (RCTs or CCTs) that compared topical or oral NSAIDs with placebo or another intervention, or compared two NSAIDs in adults with lateral elbow pain. Outcomes of interest were pain, function, quality of life, pain-free grip strength, overall treatment success, work loss and adverse effects. Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment. Fifteen trials, involving 759 participants and reporting 17 comparisons, were included in the review. Four new trials identified from the updated search were included, along with 11 of 14 trials included in the original review (three trials included in the previous review were found not to meet inclusion criteria). Of eight trials that studied topical NSAIDs (301 participants), five compared topical NSAIDs with placebo, one compared manipulative therapy and topical NSAIDs with manipulative therapy alone, one compared leech therapy with topical NSAIDs and one compared two different topical NSAIDs. Of seven trials that investigated oral NSAIDs (437 participants), two compared oral NSAIDs with placebo, one compared oral NSAIDs and bandaging with bandaging alone, three compared oral NSAIDs with glucocorticoid injection, one compared oral NSAIDs with a vasodilator and two compared two different oral NSAIDs. No trials directly compared topical NSAIDs with oral NSAIDs. Few trials used intention-to-treat analysis, and the sample size of most was small. The median follow-up was 2 weeks (range 1 week to 1 year).Low-quality evidence was obtained from three trials (153 participants) suggesting that topical NSAIDs were significantly more effective than placebo with respect to pain in the short term (mean difference -1.64, 95% confidence interval (CI) -2.42 to -0.86) and number needed to treat to benefit (7 (95% CI 3 to 21) on a 0 to 10 scale). Low-quality evidence was obtained from one trial (85 participants) indicating that significantly more participants report fair, good or excellent effectiveness with topical NSAIDs versus placebo at 28 days (14 days of therapy) (risk ratio (RR) 1.49, 95% CI 1.04 to 2.14). No participants withdrew as the result of adverse events, but some studies reported mild adverse effects such as rash in 2.5% of those exposed to topical NSAIDs compared with 1.3% of those exposed to placebo.Low-quality and conflicting evidence regarding the benefits of oral NSAIDs obtained from two trials could not be pooled. One trial found significantly greater improvement in pain compared with placebo, and the other trial found no between-group differences; neither trial found differences in function. One trial reported a withdrawal due to adverse effects for a participant in the NSAIDs group. Use of oral NSAIDs was associated with increased risk of gastrointestinal side effects compared with placebo in one trial in the review. Another trial reported discontinuation of treatment due to gastrointestinal side effects in four participants taking NSAIDs, and another participant developed an allergic reaction in response to oral NSAIDs.Very scant and conflicting evidence regarding the comparative effects of oral NSAIDs and glucocorticoid injection was obtained. One trial reported a significant improvement in pain with glucocorticoid injection, and another found no between-group differences; treatment success was similar between groups (RR of fair, good or excellent effectiveness 0.74; 95% CI 0.43 to 1.26). Transient pain may occur following injection. There remains limited evidence from which to draw firm conclusions about the benefits or harms of topical or oral NSAIDs in treating lateral elbow pain. Although data from five placebo-controlled trials suggest that topical NSAIDs may be beneficial in improving pain (for up to 4 weeks), non-normal distribution of data and other methodological issues precluded firm conclusions. Some people may expect a mild transient skin rash. Evidence about the benefits of oral NSAIDs has been conflicting, although oral NSAID use may result in gastrointestinal adverse effects in some people. No direct comparisons between oral and topical NSAIDs were available. Some trials demonstrated greater benefit from glucocorticoid injection than from NSAIDs in the short term, but this was not apparent in all studies and was not apparent by 6 months in the only study that included longer-term outcomes.

  • Research Article
  • Cite Count Icon 4
  • 10.1007/s40266-018-0585-8
Factors Related to the Use of Topical vs. Oral NSAIDs for Sprains, Strains, and Contusions in a Senior Population: A Retrospective Analysis of Administrative Claims Data.
  • Sep 11, 2018
  • Drugs &amp; Aging
  • Richard Sheer + 6 more

Research to date on sprains, strains, and contusions has focused mainly on the analysis of sports-related injuries, occupational injuries, injuries resulting from automobile accidents, and severe injuries that result in inpatient hospital stays. Little is known about real-world acute sprains, strains, and contusions in an aging population. Patients may be treated with over-the-counter, oral, non-steroidal anti-inflammatory drugs (NSAIDs) for acute sprains, strains, and contusions or may require the use of prescription NSAIDs. For sprains, strains, and contusions treated with prescription NSAIDs, the choice of topical administration or oral administration likely depends on a number of factors such as age and comorbid conditions. The objective of the study was to identify factors associated with the use of a prescription topical NSAID or a prescription oral NSAID for the treatment of sprains, strains, and contusions among patients aged 65-89years enrolled in the Medicare Advantage with Prescription Drug plan. The study sample was selected from the Humana Research Database (Louisville, KY, USA). Study subjects were identified as patients enrolled in Medicare Advantage with Prescription Drug plans, aged 65-89years, having a medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification indicative of an acute sprain, strain, and contusion between 1 January, 2010 and 31 March, 2014 (identification period). The date of the first claim was considered the index date, and subjects were required to have 12 months of continuous enrollment before the index date and a minimum of 3 months continuous enrollment after the index date. Prescription NSAID use during the 3 months after the index sprain, strain, and contusion diagnosis was required for study inclusion and was identified based on a pharmacy claim for a topical or an oral NSAID. Patients with prescription NSAID use leading up to the sprains, strains, and contusions were excluded. Potential factors related to the use of a topical vs. oral NSAID were identified using stepwise logistic regression with backward elimination. After applying the inclusion and exclusion criteria, 42,283 patients were prescribed an oral or topical NSAID (39,294 oral; 2989 topical) within 3 months of the index sprain, strain, and contusion diagnosis. After applying stepwise logistic regression, and retaining variables with statistically significant parameter estimates (p < 0.05), use of topical NSAIDs was higher among female individuals [odds ratio and 95% confidence interval = 1.34 (1.24-1.45)], and appeared to increase with age [odds ratio = 1.04 (1.04-1.05)]. Topical NSAID use was lower in the Midwest region [odds ratio = 0.85 (0.77-0.94)] in comparison to the Southern region. Clinical factors associated with topical NSAID use included Elixhauser Comorbidity Index score [odds ratio = 1.06 (1.04-1.09)], medication burden [odds ratio = 1.06 (1.04-1.08), pill burden [odds ratio = 1.02 (1.01-1.03), specific comorbid conditions, including site-specific osteoarthritis of the upper arm [odds ratio = 2.34 (1.19-4.60)], ankle/foot [odds ratio = 1.46 (1.14-1.87)], or lower leg [odds ratio = 1.21 (1.07-1.36)], myofascial pain [odds ratio = 1.31 (1.21-1.42)], gastrointestinal/hepatic disorders [odds ratio = 1.15 (1.05-1.25)], systemic/central pain [odds ratio = 1.12 (1.01-1.23)], and cataracts [odds ratio = 1.10 (1.02-1.20)]. Conversely, a diagnosis of diabetes mellitus was related to use of an oral NSAID rather than a topical NSAID [odds ratio = 0.86 (0.78-0.94)]. Diagnosis of the index sprain, strain, and contusion in an emergency department instead of a physician's office was also associated with oral NSAID use [odds ratio = 0.42 (0.37-0.47)]. Topical NSAIDs were used less often than oral NSAIDs following a sprain, strain, or contusion. Age, medication burden, pill burden, evidence of gastrointestinal disorder, and evidence of certain pain-related conditions were significant factors associated with topical NSAID as opposed to oral NSAID use. In comparison to oral NSAIDs, topical NSAIDs were more likely to be prescribed in a physician's office than an emergency department, possibly because a patient's physician has a better understanding of the patient's concomitant medications and comorbidities. Although topical NSAIDs were more likely to be used than oral NSAIDs in patients with gastrointestinal disorders, the use of oral NSAIDs among patients with gastrointestinal bleeding was substantial.

  • Research Article
  • Cite Count Icon 72
  • 10.3810/psm.2013.05.2016
Effectiveness and Safety of Topical versus Oral Nonsteroidal Anti-inflammatory Drugs: A Comprehensive Review
  • May 1, 2013
  • The Physician and Sportsmedicine
  • Stephen A Klinge + 1 more

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.

  • Discussion
  • Cite Count Icon 4
  • 10.1097/corr.0000000000000486
Cochrane in CORR®: Topical NSAIDs for Chronic Musculoskeletal Pain in Adults.
  • Sep 22, 2018
  • Clinical orthopaedics and related research
  • Anthony Adili + 1 more

Cochrane in CORR®: Topical NSAIDs for Chronic Musculoskeletal Pain in Adults.

  • Front Matter
  • Cite Count Icon 189
  • 10.1016/j.semarthrit.2015.11.007
Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys.
  • Dec 2, 2015
  • Seminars in Arthritis and Rheumatism
  • François Rannou + 2 more

Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys.

  • Research Article
  • Cite Count Icon 60
  • 10.3310/hta12220
Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study.
  • May 1, 2008
  • Health technology assessment (Winchester, England)
  • M Underwood + 13 more

To determine whether GPs should advise their older patients with chronic knee pain to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs). An equivalence study was designed to compare the effect of advice to use preferentially oral or topical ibuprofen (an NSAID) on knee pain and disability, NSAID-related adverse effects and NHS/societal costs, using a randomised controlled trial (RCT) and a patient preference study (PPS). Reasons for patient preferences for topical or oral preparations, and attitudes to adverse effects, were explored in a qualitative study. Twenty-six general practices in the UK. Participants comprised 585 people with knee pain, aged 50 years or over; 44% were male, mean age 64 years. The RCT had 282 participants: 144 in the oral group and 138 in the topical group. The PPS had 303 participants: 79 in the oral group and 224 in the topical group. Advice to use preferentially oral or topical NSAIDs for knee pain. The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the Short Form with 36 Items (SF-36), perceived troublesomeness of knee pain, satisfaction with health status, major adverse effects (unplanned hospital admissions and deaths) and minor adverse events over 12 months. The health economic analysis measured the comparative cost per quality-adjusted life-year (QALY) from both an NHS and a societal perspective over 1 and 2 years. Changes in the global WOMAC score at 12-months were equivalent in both studies: topical - oral, RCT difference=2 [95% confidence interval (CI) -2 to 6], PPS difference=1 (95% CI -4 to 6). There were no differences in the secondary outcomes, except for a suggestion, in the RCT, that those in the topical group were more likely to have more severe overall pain and disability as measured by the chronic pain grade, and more likely to report changing treatment because of inadequate pain relief. There were no differences in the rate of major adverse effects but some differences in the number of minor ones. In the RCT, 17% and 10% in the oral and the topical group, respectively, had a defined respiratory adverse effect (95% CI of difference -17% to -2.0%); after 12 months, the change in serum creatinine was 3.7 mmol/l (95% CI 0.9 to 6.5) less favourable in the oral than in the topical group, and 11% of those in the oral group reported changing treatment because of adverse effects compared with 1% in the topical group (p=0.02). None of these differences were seen in the PPS. Oral NSAIDs cost the NHS 191 pounds and 72 pounds more per participant over 1 year in the RCT and PPS respectively. In the RCT the cost per QALY in the oral group, from an NHS perspective, was in the range 9000-12,000 pounds. In the PPS it was 2564 pounds over 1 year, but over 2 years the oral route was more cost-effective. Patient preference for medication type was affected by previous experience of medication (including adverse reactions), other illness, pain elsewhere, anecdotes, convenience, severity of pain and perceived degree of degeneration. Lack of understanding about knee pain and the action of medication led to increased tolerance of symptoms. Potentially important symptoms may inadvertently have been disregarded, increasing participants' risk of suffering a major adverse effect. Advice to use either oral or topical preparations has an equivalent effect on knee pain, but oral NSAIDs appear to produce more minor adverse effects than topical NSAIDs. Generally, these results support advising older people with knee pain to use topical rather than oral NSAIDS. However, for patients who prefer oral NSAID preparations rather than a topical NSAID, particularly those with more widespread or severe pain, the oral route is a reasonable treatment option, provided that patients are aware of the risks of potentially serious adverse effects from oral medication. Further research is needed into strategies to change prescribing behaviour and ensure that older patients are aware of the potential risks and benefits of using NSAIDs. Observational studies are needed to estimate rates of different predefined minor adverse effects associated with the use of oral NSAIDs in older people as are long-term studies of topical NSAIDs in those for whom oral NSAIDs are not appropriate.

  • Research Article
  • Cite Count Icon 126
  • 10.1002/14651858.cd007400.pub2
Topical NSAIDs for chronic musculoskeletal pain in adults.
  • Sep 12, 2012
  • The Cochrane database of systematic reviews
  • Sheena Derry + 2 more

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken orally, but they are also available in topical preparations to be applied to or rubbed onto the skin of a painful joint, typically one affected by arthritis, with the aim of relieving pain locally. Topical NSAIDs are widely used in some parts of the world for acute and chronic painful conditions, but have not been universally accepted until recently. One of the problems has been that older clinical studies were generally short, lasting four weeks or less, and short duration studies are not regarded as adequate in ongoing painful conditions. To examine the use of topical NSAIDs in chronic musculoskeletal pain, focusing on studies of high methodological quality, and examining the measured effect of the preparations according to study duration. The principal aim was to estimate treatment efficacy in longer duration studies of at least 8 weeks. A series of electronic searches, together with bibliographic searches, and searches of in-house databases were combined with electronic searches of clinical trial registers and manufacturers of topical NSAIDs, or companies known to be actively researching topical NSAIDs. There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Randomised, double blind studies with placebo or active comparators, where at least one treatment was a topical NSAID product, in any topical formulation (cream, gel, patch, solution), in studies lasting at least two weeks. Two review authors independently assessed study quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk (RR) and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Information was available from 7688 participants in 34 studies from 32 publications; 23 studies compared a topical NSAID with placebo. Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal conditions. The best data were for topical diclofenac in osteoarthritis, where the NNT for at least 50% pain relief over 8 to 12 weeks compared with placebo was 6.4 for the solution, and 11 for the gel formulation. There were too few data of good quality to calculate NNTs for other individual topical NSAIDs compared with placebo. Direct comparison of topical NSAID with an oral NSAID did not show any difference in efficacy. There was an increase in local adverse events (mostly mild skin reactions) with topical NSAIDs compared with placebo or oral NSAIDs, but no increase in serious adverse events. Gastrointestinal adverse events with topical NSAID did not differ from placebo, but were less frequent than with oral NSAIDs.A substantial amount of data from unpublished studies was unavailable. Much of this probably relates to formulations that have never been marketed. Topical NSAIDs can provide good levels of pain relief; topical diclofenac solution is equivalent to that of oral NSAIDs in knee and hand osteoarthritis, but there is no evidence for other chronic painful conditions. Formulation can influence efficacy. The incidence of local adverse events is increased with topical NSAIDs, but gastrointestinal adverse events are reduced compared with oral NSAIDs.

  • Research Article
  • Cite Count Icon 245
  • 10.1002/14651858.cd007400.pub3
Topical NSAIDs for chronic musculoskeletal pain in adults.
  • Apr 22, 2016
  • The Cochrane database of systematic reviews
  • Sheena Derry + 4 more

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. 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. 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. 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. 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. 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. 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.

  • Research Article
  • Cite Count Icon 11
  • 10.1002/pds.4866
NSAID use among residents in 68 residential aged care facilities 2014 to 2017: An analysis of duration, concomitant medication use, and high-risk conditions.
  • Aug 6, 2019
  • Pharmacoepidemiology and Drug Safety
  • Kimberly E Lind + 3 more

People in residential aged care are at increased risk of adverse events from nonsteroidal anti-inflammatory drugs (NSAIDs) due to their age and health status, but little is known about use of NSAIDs in this setting. We aimed to estimate the prevalence of NSAID use by route, differences by high-risk conditions, prevalence of concurrent proton pump inhibitor (PPI) use, and prevalence of the "triple whammy" combination (oral NSAID, diuretic, and angiotensin-converting-enzyme inhibitor or angiotensin receptor antagonist). We conducted a dynamic cohort study using medication administration data from 68 residential aged care facilities (RACFs) during 2014 to 2017. Descriptive statistics and regression were used to estimate the proportion of residents who used NSAIDs, NSAIDs long term, NSAIDs with PPIs, and the triple whammy combination. Ten thousand three hundred sixty-seven residents were included. Two thousand four hundred fourteen (23.3%) used at least one NSAID: 756 (7.3%) used only oral, 1326 (12.8%) used only topical, and 332 (3.2%) used both topical and oral NSAIDs. One thousand five hundred forty two (14.8%) used an NSAID long term, a majority of which only used topical NSAIDs 933/1542 (60.5%). Age, sex, and health status were associated with greater variation in long-term topical use relative to oral NSAID use. A majority of oral NSAID users concomitantly used a PPI, which varied according to age, sex, and health status. Among residents with any oral NSAID use, 182/1088 (16.7%) had triple whammy medication use. Targeted interventions to reduce NSAID use among RACF residents, to reduce triple whammy medication use, and increase PPI use for long-term oral NSAID users are warranted.

  • Discussion
  • Cite Count Icon 3
  • 10.1136/ebmed-2016-110406
Topical NSAIDs significantly reduces pain in adults with acute musculoskeletal injuries.
  • Aug 12, 2016
  • Evidence-based medicine
  • Gwendolyn Vuurberg + 1 more

Commentary on: Derry S, Moore RA, Gaskell H, et al. Topical NSAIDs for acute musculoskeletal pain in adults. Cochrane Database Syst Rev 2015;(6):CD007402. Use of topical non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief is widely controversial in analgesic practice.1 For the topical NSAIDs to have an effect on acute pain, the formulation has to penetrate the skin. The expected advantages of this type of administration are both potential minimisation of systemic side effects and increase of local effect. However, there is still debate on these potential advantages as there is continuous lack of significant positive results.2–4 A Cochrane review update was recently carried out to assess the effect of topical NSAIDs used for acute musculoskeletal pain in adults.5 This review aimed to strengthen conclusions on the efficacy and safety of topically applied NSAIDs in acute musculoskeletal pain in adults, adding recently published studies to the previous search. The review included only double-blinded …

  • Research Article
  • 10.54393/pjhs.v6i9.3265
Comparison of The Efficacy of Oral Versus Topical NSAIDs for Pain Relief in Osteoarthritis
  • Sep 30, 2025
  • Pakistan Journal of Health Sciences
  • Alam Zeb + 5 more

Osteoarthritis is a leading cause of chronic musculoskeletal pain worldwide, significantly impairing quality of life and increasing healthcare burden. Nonsteroidal anti-inflammatory drugs (NSAIDs), administered orally or topically, remain the mainstay of symptom management, though their relative efficacy and safety profiles require further evaluation. Objectives: To compare the efficacy of oral versus topical NSAIDs for pain relief in osteoarthritis. Methods: This quasi-experimental study was conducted at the Department of Rheumatology, Khyber Teaching Hospital, Peshawar, during the period February 2025 to May 2025. 132 male and female patients aged more than 50 years diagnosed with osteoarthritis were assigned to topical (n=66) and oral NSAID (n=66) groups. Diclofenac gel and tablet diclofenac 50mg BD were administered for 4 weeks, respectively. Patients were evaluated for pain relief using the VAS score. Results: Mean age in topical versus oral NSAIDs was 64.73±8.25 years versus 66.55±9.606 years, respectively. Male participants were 41 (52.6%) and 37(47.4%) in topical and oral groups, respectively. 23(50.0%) had bilateral joint involvement in both groups. Pain relief was recorded in 25 patients (37.9%) with topical NSAIDs compared to 35 (53.1%) with oral NSAIDs (p-value 0.080). Conclusions: Statistically insignificant difference in pain relief was recorded with topical and oral NSAIDs in patients with chronic MSK pain of osteoarthritis. Though the proportion of pain relief was better with oral NSAIDs, the difference was statistically not significant.

  • Research Article
  • 10.18203/2394-6040.ijcmph20243449
Comparing the incidence of adverse events following topical versus oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: a systematic review and meta-analysis
  • Nov 21, 2024
  • International Journal Of Community Medicine And Public Health
  • Maryam S Alsharif + 6 more

Knee osteoarthritis is a prevalent condition that significantly impairs the quality of life, often managed with non-steroidal anti-inflammatory drugs (NSAIDs). While oral NSAIDs are widely used for their systemic effects, they are associated with a higher risk of adverse events (AEs). Topical NSAIDs offer localized approach with potentially fewer systemic side effects, making them an alternative. This meta-analysis compared the incidence of overall AEs associated with topical versus oral NSAIDs in patients with knee osteoarthritis. A systematic search was conducted in PubMed, Cochrane Library, and Embase for studies comparing AEs in patients with knee osteoarthritis treated with topical versus oral NSAIDs. Eight studies with a total of 2,181 participants were included. The pooled odds ratio (OR) for overall AEs was calculated, and heterogeneity among studies was assessed using I² statistic. Publication bias was evaluated using a funnel plot. The meta-analysis demonstrated that topical NSAIDs were associated with lower incidence of AEs compared to oral NSAIDs, with a pooled OR of 0.62 (95% CI: 0.38 to 1.00). This suggests that patients treated with topical NSAIDs were 38% less likely to experience AEs than those treated with oral NSAIDs (p=0.05). Significant heterogeneity was observed among the studies (I²=80%). The funnel plot indicated potential publication bias. Topical NSAIDs offer safer alternative to oral NSAIDs for managing knee osteoarthritis, particularly in reducing the risk of AEs. While the findings are promising, the high degree of heterogeneity and potential publication bias underscore the need for further research to confirm these results.

  • Research Article
  • Cite Count Icon 83
  • 10.1002/14651858.cd003686
Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults.
  • Oct 23, 2001
  • The Cochrane database of systematic reviews
  • Sally Green + 6 more

Lateral elbow pain, or tennis elbow, is a common condition causing pain in the elbow and forearm and lack of strength and function of the elbow and wrist. It is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), either orally or by topical application. To assess effectiveness of NSAIDs (oral or topical) in the treatment of adults with lateral elbow pain with respect to symptom (pain) reduction, improvement in function, grip strength and adverse effects. We searched the Musculoskeletal Review Group's trials register database, the Cochrane Clinical Trials Register (Cochrane Library issue 2, 2001), MEDLINE, CINAHL, EMBASE and SCISEARCH up to June 2001. Randomised and pseudo randomised trials in all languages of NSAIDs (oral or topical) compared to placebo or another intervention, or comparing two NSAIDs (oral or topical) to each other, in adults with lateral elbow pain (tennis elbow). Outcomes of interest were pain, function, disability and quality of life, strength, participant satisfaction with treatment and adverse effect. Two reviewers independently applied selection criteria and assessed study quality. Fourteen trials were included in the review. Few trials used intention to treat analysis, and the sample size of most was small. The median follow up was 2 weeks (range 1-12 weeks). There is evidence that topical NSAIDs are significantly more effective than placebo with respect to pain [weighted main difference= -1.88, (95% confidence intervals -2.54 to -1.21)] and participant satisfaction [relative risk 0.39, (95% confidence intervals 0.23 to 0.66)] in the short term, and this finding is robust against the possible bias introduced by the inclusion of unblinded trials and publication bias. The adverse effects reported were minor. Only two included trials assessed the effect of oral NSAID and these were not able to be pooled. There is some evidence for short term benefit with respect to pain and function from oral NSAIDs, but this benefit was not sustained. Significantly more gastrointestinal adverse effects were reported by those taking oral NSAIDs [relative risk = 3.17, (95% confidence intervals 1.35 to 7.41)]. In the short term there may be some advantage in steroid injection over oral NSAID [patient's perception of benefit relative risk = 3.06, (95% confidence intervals 1.55 to 6.06)], but this was not sustained in the longer term. There is some support for the use of topical NSAIDs to relieve lateral elbow pain at least in the short term. There remains insufficient evidence to recommend or discourage the use of oral NSAID, although it appears injection may be more effective than oral NSAID in the short term. A direct comparison between topical and oral NSAID has not been made and so no conclusions can be drawn regarding the best method of administration.

  • Research Article
  • Cite Count Icon 53
  • 10.1136/bmj.39401.699063.be
Influences on older people’s decision making regarding choice of topical or oral NSAIDs for knee pain: qualitative study
  • Dec 4, 2007
  • BMJ (Clinical research ed.)
  • Dawn Carnes + 4 more

Objective To explore the factors that influence older people’s decision making regarding use of topical or oral ibuprofen for their knee pain.Design Qualitative interview study nested within a randomised controlled...

  • Research Article
  • Cite Count Icon 14
  • 10.1097/md.0000000000030354
Relative safety and efficacy of topical and oral NSAIDs in the treatment of osteoarthritis: A systematic review and meta-analysis.
  • Sep 9, 2022
  • Medicine
  • Yuhui Wang + 8 more

Osteoarthritis (OA) often affects the hands, knees, and hip joints, causing considerable pain and disability, and often affecting the patient's quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are common pain relievers often applied as first line therapies for OA. However, prolonged NSAIDs application can have unwanted side effects. Given this, this study was designed to systematically evaluate the efficacy and safety of topical and oral NSAIDs for the treatment of OA. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant papers from their inception dates to May 2021. Our study only included randomized controlled trials comparing topical and oral NSAIDs and all data were analyzed using Review Manager version 5.3 (RevMan version 5.3). We identified 8 RCTs (2096 patients with OA), for evaluation and revealed that, in general, topical and oral NSAIDs presented with similar efficacies for the treatment of OA. The Western Ontario and McMaster Osteoarthritis Index for assessing pain relief in OA patients was (standardized mean difference [SMD] 0.07; 95%CI -0.02, 0.17) and visual analog scale was (SMD -0.01; 95%CI -0.02, 0.18), and improved stiffness in OA patients (SMD 0.09; 95%Cl 0.03, 0.20). Topical NSAIDs are as effective as oral NSAIDs for the treatment of OA and both topical and oral NSAIDs are equally effective in reducing pain and improving physical function in OA patients. In terms of safety, a larger number of samples are still needed to determine if there are any differences in the safety profile of topical or oral NSAIDs. INPLASY 2021110009.

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