1. Introduction

This guide summarizes clinical evidence on the effectiveness and safety of non-opioid analgesics for osteoarthritis. It covers most available over-the-counter (OTC) medications and prescription non-steroidal anti-inflammatory drugs (NSAIDs). The reviewed drugs are listed in section 8. This guide does not address nonpharmacologic therapies such as diet, exercise, acupuncture, or surgical interventions.

Clinical Issue

Twenty-one million Americans have osteoarthritis. It is a chronic condition associated with pain and substantial disability. Managing pain can assist in maintaining mobility and improving quality of life. Choosing among the available prescription and over-the-counter medications requires careful consideration of benefits, risks, and cost.

The categories of non-opioid drug treatments for osteoarthritis are:

• Acetaminophen.
• NSAIDs, including aspirin and celecoxib.
• Glucosamine and chondroitin.
• Topical medications (including capsaicin, topical salicylates, and topical NSAIDs).

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2. Clinical Bottom Line

Confidence Scale

The confidence ratings in this guide are derived from a systematic review of the literature. The level of confidence is based on the overall quantity and quality of clinical evidence.

High

There are consistent results from good quality studies.

Medium

Findings are supported, but further research could change the conclusions.

Low

There are very few studies, or existing studies are flawed.

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3. GI Bleeding Risk

The most frequent serious complication is gastrointestinal (GI) bleeding due to gastric irritation. Age is one important factor that affects a person’s risk, as shown in the box below.

Strategies to Lower the Risk of GI Bleeding

• Avoid NSAIDs for people with a history of GI bleeding.
  
  Level of confidence:
• Avoid NSAIDs for people on anticoagulant therapy.
  
  Level of confidence:
• Consider acetaminophen. It is associated with a lower risk of GI bleeding than NSAIDs.
  
  Level of confidence:
• Consider co-prescribing proton pump inhibitors (PPIs) or misoprostol. These drugs are effective in reducing GI bleeding for people on NSAIDs. Misoprostol is poorly tolerated by many individuals due to its GI side effects.
  
  Level of confidence:
• Consider celecoxib. Results from short-term trials indicate it has a lower risk of GI bleeding than other NSAIDs. Concomitant use of aspirin (even low dose) reduces or negates the benefit of using celecoxib.
  
  Level of confidence:

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4. Other Risks

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5. Alternatives to Oral NSAIDs

• Acetaminophen. For mild pain, it is an effective alternative to NSAIDs.
  
Level of confidence:
• Capsaicin cream. It relieves chronic osteoarthritic pain, but about half of the people using it will experience local burning sensations. The burning diminishes over time.
  
  Level of confidence:
• Topical creams containing prescription NSAIDs. They work as well as oral NSAIDs for osteoarthritic pain relief and have fewer systemic side effects. Topical diclofenac and topical ibuprofen are the best studied topicals. The FDA has not approved any topical NSAID formulations, but compounding is widely available.
  
  Level of confidence:
• Glucosamine and chondroitin. Used alone or together, glucosamine and chondroitin do not bring clinically significant improvement in joint pain or functioning. One clinical trial evaluated a subgroup of people with moderate to severe osteoarthritis. This trial found that people in the subgroup had improved pain and joint function compared with a group of people treated with a placebo. The Food and Drug Administration (FDA) does not regulate these supplements as drugs, so their purity may vary.
  
  Level of confidence:

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6. Resources for Patients

Consumer Guide

Choosing Pain Medicine for Osteoarthritis: A Guide for Consumers is a companion to this Clinician’s Guide. It can help people talk with their health care professional about pain relief options. It provides information about:

• Types of over-the-counter and prescription pain relievers.
• Benefits, risks, and price of pain relievers.

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7. Still Unknown

• There have been few studies comparing aspirin or salsalate to other NSAIDs for the treatment of osteoarthritis.
• We do not have enough data to make reliable judgments about the cardiovascular risks of many oral NSAIDs. The drugs most studied are celecoxib, ibuprofen, diclofenac, and naproxen.
• There is insufficient evidence to assess whether therapeutic doses (up to 4 grams a day) of acetaminophen lead to liver abnormalities in people without underlying liver disease.
• Results from recent observational studies suggest an increased cardiovascular risk with heavy use of acetaminophen, but large, long-term trials of acetaminophen and associated cardiovascular safety are lacking.
• It is not known whether using celecoxib is a better strategy than adding a PPI or misoprostol to a conventional NSAID for lowering the risk of GI bleeding.

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8. Price

¹These drugs were evaluated in the systematic review.
²OTC brand names were selected based on OTC sales in 2005.
³Average Wholesale Price is from Drug Topics Redbook, 2006.
EC = enteric coated, XR/ER = extended release, SR = sustained release, bid = twice a day, tid = three times a day, NA = not available.

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9. Source

The source material for this guide is a systematic review of 351 research publications. The review, Comparative Effectiveness and Safety of Analgesics for Osteoarthritis (2006), was prepared by the Oregon Evidence-based Practice Center. The Agency for Healthcare Research and Quality (AHRQ) funded the systematic review and this guide. The guide was developed using feedback from clinicians who reviewed preliminary drafts.

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10. For More Information

Visit the Consumer Guide Choosing Pain Medicine for Osteoarthritis.

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