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Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal Anti-Inflammatory DrugsRelevance to family physicians

Musculoskeletal problems are Canada’s leading cause of long-term disability. In the general population, they are among the most frequent chronic health conditions, reasons for seeing a doctor, and reasons for using prescription and nonprescription drugs. Just over 10% of office visits to general practitioners and family physicians are attributable to these disorders.

More than half of these visits are for nonspecific musculoskeletal conditions, osteoarthritis, and soft-tissue rheumatism (tendonitis, bursitis). The prevalence of arthritis is projected to increase dramatically; between 1991 and 2031, a 47% increase is expected as well as a 124% rise in the number of people affected.

Several interventions have been found to be effective for osteoarthritis, the single most frequent specific diagnosis. Aerobic and muscle-strengthening exercises and education provide benefits in the form of pain relief, increased function, and self-efficacy. Acetaminophen in adequate doses (4 g/d) provides pain relief that is comparable to that provided by oral nonsteroidal anti-inflammatory drugs (NSAIDs). Both Canadian practice guidelines under development and United States practice guidelines recommend acetaminophen as first-line therapy. Topical rubs are second-line therapy in current US recommendations; oral NSAIDs are third-line.

For patients with conditions such as osteoarthritis who do not always get adequate pain relief from non-pharmacologic interventions plus acetaminophen, a trial of oral nonsteroidal anti-inflammatory drugs is customary. Oral NSAIDs have potentially serious gastrointestinal effects: the annual attributable risk of hospitalization for gastrointestinal problems is 1.3% to 1.6% for regular users. In addition to potential gastrointestinal problems, many patients have risk factors, such as renal failure or congestive heart failure, that weigh against long-term use of nonsteroidal anti-inflammatory drugs.

The promise of an effective topical treatment for musculoskeletal conditions is appealing. An ideal medication would penetrate into the underlying joint, provide pain relief, not enter the bloodstream in appreciable amounts, cause no systemic adverse effects, and have few local reactions. Because many people already use topical rubs of various kinds, they might prefer this route of administration.

At least 15 topical nonsteroidal anti-inflammatory drugs are available worldwide. Their use in Canada has been limited, and they are not currently approved for musculoskeletal indications. Despite this, at least two agents, ketoprofen and naproxen, can be compounded by Canadian pharmacists. To date, these compounds have been used primarily in sports medicine. Canadian physicians might be asked about their use by patients who have obtained the drugs during visits to other countries.

Are these medications effective and safe? Given the lack of acceptable alternatives for pain relief for many of our patients, what should we recommend?

Overview of study and outcome

The authors included studies of topical nonsteroidal anti-inflammatory drugs that were randomized; had pain as an outcome for acute conditions (sprains, strains, sports injuries) or chronic conditions (arthritis, rheumatism); and had a comparison group that used another topical NSAID, a placebo, or an oral nonsteroidal anti-inflammatory drug. Their search strategies encompassed MEDLINE, EMBASE, and the Oxford Pain Relief Database in all languages. They identified further reports from reference lists of retrieved articles, and they contacted 12 pharmaceutical manufacturers in the United Kingdom to seek out unpublished studies. They did not contact the authors of the studies they identified, nor did they include abstracts.

Two authors screened the reports to eliminate those that definitely did not meet inclusion criteria, and then each remaining report was read by all authors independently. Trial quality was scored according to whether randomization was performed and described; blinding was present, described, and adequate; and withdrawals were described and explained. Only information available in dichotomous form was used for analysis, and analyses were framed on an intent-to-treat basis (subjects were analyzed in the groups to which they were allocated whether or not they used the assigned study medications). A measure of effectiveness was taken 1 week after start of treatment for acute conditions and 2 weeks after for chronic conditions. Treatment success was defined as a 50% or greater reduction in pain.

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