Friday, June 1, 2007

Choosing Non-Opioid Analgesics for Osteoarthritis

The following are the most recent guidelines for treatment of pain caused by osteoarthritis. This information is provided by the United States Department of Health & Human Services, Agency for Healthcare Research and Quality.

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 on the back page. This guide does not address non-pharmacologic 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).

CLINICAL BOTTOM LINE

Acetaminophen relieves mild pain but is inferior to NSAIDs for reducing moderate or severe pain. Acetaminophen has fewer systemic side effects than NSAIDs. Level of confidence: HIGH. There are consistent results from good quality studies.

All non-aspirin NSAIDs work equally well for pain reduction. Level of confidence: HIGH. There are consistent results from good quality studies.

NSAIDs increase the risk of GI bleeding. The risk increases with higher doses and with age. People over 75 years old have the highest risk. Level of confidence: HIGH. There are consistent results from good quality studies.

Celecoxib, high dose ibuprofen, and high dose diclofenac increase the risk of myocardial infarction. Naproxen does not increase the risk of myocardial infarction. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

Capsaicin cream 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: MEDIUM. Findings are supported, but further research could change the conclusions.

Topical salicylates do not reduce osteoarthritic pain. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

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.

Risk of NSAID-Associated GI Bleeding Increases with Age

- For people age 16-44:
5 of 10,000 people on NSAIDs will have a serious GI bleed
1 of 10,000 people on NSAIDs will die from a GI bleed
- For people age 45-64:
15 of 10,000 people taking NSAIDs will have a serious GI bleed
2 of 10,000 people taking NSAIDs will die from a GI bleed
- For people age 65-74:
17 of 10,000 people taking NSAIDs will have a serious GI bleed
3 of 10,000 people taking NSAIDs will die from a GI bleed
- For people age 75 or older:
91 of 10,000 people taking NSAIDs will have a serious GI bleed
15 of 10,000 people taking NSAIDs will die from a GI bleed

Strategies to Lower the Risk of GI Bleeding

- Avoid NSAIDs for people with a history of GI bleeding. Level of confidence: HIGH. There are consistent results from good quality studies.

- Avoid NSAIDs for people on anticoagulant therapy. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Consider acetaminophen. It is associated with a lower risk of GI bleeding than NSAIDs. Level of confidence: HIGH. There are consistent results from good quality studies.

- 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: HIGH. There are consistent results from good quality studies.

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

CARDIOVASCULAR RISK

The cardiovascular risk of NSAIDs has received considerable attention. In general, the increased risk of myocardial infarction for any of the NSAIDs other than naproxen is about 30 per 10,000 people taking NSAIDs per year.

- Celecoxib, ibuprofen at high doses (800 mg three times a day), and diclofenac at high doses (75 mg twice a day) have a higher risk of myocardial infarction compared to not taking these medications. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Naproxen, even at high doses (500 mg twice a day), does not increase the risk of myocardial infarction. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- For other oral NSAIDs, we do not have enough data on cardiovascular risks to make reliable judgments.

HEPATOTOXICITY RISK

- Clinically significant hepatotoxicity is rare for all the NSAIDs in this guide. Level of confidence: HIGH. There are consistent results from good quality studies.

- Diclofenac is associated with higher rates of aminotransferase elevations (compared to other NSAIDs) but not with a higher incidence of serious liver disease. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

RENAL RISK

- All NSAIDs, including COX-2 inhibitors, can cause or aggravate hypertension, congestive heart failure, edema, and kidney problems. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- 5 mm Hg is the average increase in mean blood pressure for nonselective NSAIDs. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- 2 out of 1,000 people stop taking an NSAID because of renal problems. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Long-term, regular acetaminophen use is associated with a small decrease in renal function in women but not in men. In people without underlying renal disease, this decrease is unlikely to progress to clinically significant renal failure. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

ALTERNATIVES TO ORAL NSAIDS

- Consider glucosamine and chondroitin. Pharmaceutical grade glucosamine hydrochloride (1500 mg a day) plus chondroitin sulfate (1200 mg a day) reduces moderate to severe pain without serious side effects, but this combination has no effect on mild pain. The Food and Drug Administration (FDA) does not regulate these supplements as drugs, so the purity may vary. Level of confidence: MEDIUM. Findings are supported, but further research could change the conclusions.

- Consider acetaminophen. For mild pain, it is an effective alternative to NSAIDs. Level of confidence: HIGH. There are consistent results from good quality studies.

- Consider 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: MEDIUM. Findings are supported, but further research could change the conclusions.

- Consider topical 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: HIGH. There are consistent results from good quality studies.

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 gm 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.

PRICE
[Please refer to table on line at this link for price information.]

RESOURCE 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.

SOURCE
The source material for this guide is a systematic review of 351 research publications, Comparative Effectiveness and Safety of Analgesics for Osteoarthritis (2006). The Agency for Healthcare Research and Quality (AHRQ) funded the systematic review and this guide. AHRQ's John M. Eisenberg Center at Oregon Health and Science University developed this guide using feedback from clinicians who reviewed preliminary drafts.

[Osteoarthritis Clinician Guide PDF version] [Osteoarthritis Clinician Guide on-line html version]

http://www.ahrq.gov/

The above message comes from "AHRQ", who is solely responsible for its content.

2 comments:

AK said...

There's a great article on natural relief for arthritis sufferers on Healthy Direct's blog: http://www.healthydirect.co.uk/weblog/archives/2006/12/natural_relief.html

They sell Glucosamine and Omega Oils too. My wife and i have been taking the Omega Oils supplements for years now and can vouch for their effectiveness.

Bilo said...

Thank you for the reference and for sharing your experience. I am glad to see that someone is reading this ;-)