Medications

Many medications are available for relieving the symptoms of osteoarthritis. A major analysis indicated that drug therapy is generally more effective than non-drug treatments (surgery, acupuncture). However, a 2006 review of knee osteoarthritis studies found that pain-relief medications generally help only for the first 2 - 3 weeks of treatment. The following are some of the medications used in mild-to-severe cases:

• Acetaminophen
• Nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors
• Capsaicin
• Tramadol
• Narcotic pain relievers (oxycodone, oxymorphone, or morphine)
• Glucosamine and chondroitin (see Alternative and Complementary Medicine section)

Acetaminophen

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and others) is currently the first choice for treating osteoarthritis. However, several major analyses report that acetaminophen is less effective than NSAIDs in reducing moderate-to-severe pain. Because acetaminophen has fewer side effects, most experts suggest trying this drug first, then switching to an NSAID if acetaminophen does not provide sufficient pain relief.

Side Effects. Acetaminophen is inexpensive and generally safe. It poses far less of a risk for gastrointestinal problems than NSAIDs and does not appear to increase the risk for miscarriage (as NSAIDs do), even when used regularly.

It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

• Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve, Naprosyn), ketoprofen (Actron, Orudis KT).
• Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren, Cataflam), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), nabumetone (Relafen), dexibuprofen (Seractil), indomethacin (Indocin), meloxicam (Mobic, generic).
• Topical NSAIDs delivered in gels, creams, or patches do not appear to provide any long-term benefits in reducing arthritic pain. A review of clinical trial data, published in 2004, suggested that guidelines that recommend topical NSAIDs for treatment of osteoarthritis should be revised.

Many experts now recommend that patients use oral NSAIDs for only a short period of time. A 2004 review, published in the British Medical Journal, suggested that long-term use of NSAIDs does not actually reduce osteoarthritis pain and may increase patients' risk of experiencing side effects. High dosages of NSAIDs can cause heart problems (such as increased blood pressure), kidney problems, and stomach bleeding.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

A 2006 comprehensive report from the U.S. Agency for Healthcare Quality and Research indicated that both NSAIDs and COX-2 inhibitors are equally effective for pain relief and pose similar risks for heart attacks. The report found that one particular NSAID, naproxen (Aleve, Naprosyn), presents less risk of heart attack for some patients. A 2006 Journal of the American Medical Association study suggested that diclofenac (Voltaren, Cataflam) may pose a higher risk for heart attack than other NSAIDs. All patients should talk to their doctors before switching any medications.

NSAID-Induced Ulcers and Gastrointestinal Bleeding

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. Such ulcers are also more likely to bleed than those caused by the bacteria H. pylori. NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Because there are usually no gastrointestinal symptoms from NSAIDs until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding.

Among the groups at high risk for bleeding are elderly people, anyone with a history of ulcers of GI bleeding, patients with serious heart conditions, alcohol abusers, and those on certain medications, such anticoagulants ("blood thinners"), corticosteroids, or bisphosphonates (drugs used for osteoporosis). Proton-pump inhibitors may help to prevent and heal ulcers caused by NSAIDs. Proton-pump inhibitors include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid)

Drugs for Prevention NSAID-Induced Ulcers. If you have NSAID-induced ulcers, follow these steps:

• Switch to alternative pain relievers. This is the first step in preventing or healing ulcers caused by NSAIDs. If people cannot change drugs, they should use the lowest NSAID dose possible.
• Try proton-pump inhibitors (PPIs). These drugs help reduce NSAID-ulcer rates by as much as 80% compared with no treatment. Brands include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).
• Try misoprostol or Arthrotec. If other drugs are inappropriate, misoprostol protects against the major intestinal toxicity of NSAIDs. It was the first drug approved for preventing NSAID-induced ulcers. It is equally, or even more, effective than some of the PPIs, but it does not heal existing ulcers and has more side effects than PPIs. Patients tend to stop using it. Arthrotec is a combination of an ulcer protective drug called misoprostol and the NSAID diclofenac. One study found that patients taking Arthrotec had 65 - 80% fewer ulcers than those who took NSAIDs alone.

Healing Existing Ulcers. A number of drugs are available to heal NSAID-induced ulcers. Treatment takes about 2 - 6 weeks. Proton-pump inhibitors are the most effective drugs. Others that may be beneficial include sucralfate or H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac).

COX-2 Inhibitors (Coxibs)

Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of cardiovascular events, as well as skin rashes and other adverse effects, the FDA has been re-evaluating the relative risks and benefits of this drug class. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the United States market. Celecoxib (Celebrex) is still available, but patients should discuss with their doctors whether this drug is appropriate and safe for them.

A newer COX-2 inhibitor, etoricoxib (Arcoxia) is approved in 60 countries but not the United States. A 2006 Lancet study indicated that etoricoxib is similar to the NSAID diclofenac in risks for heart attack and stroke. (However, diclofenac has already been shown to have a higher risk of heart attack than any other NSAID, so some experts do not find this study result reassuring.) Etoricoxib caused more high blood pressure and fluid retention (edema) than diclofenac. Etoricoxib appeared to pose a lower risk than diclofenac for uncomplicated upper gastrointestinal problems, (obstruction, perforation, bleeding, ulcers), but there was little difference between the two drugs for more serious gastrointestinal complications. In 2007, the FDA rejected an application to market etoricoxib in the U.S.

Capsaicin

Capsaicin is a component of hot red peppers and may bring pain relief when used as a skin cream (Zostrix). This is the only skin preparation that does more than just mask pain or reduce it temporarily. Capsaicin seems to reduce a substance in the body, known as substance P, which contributes both to inflammation and the delivery of pain impulses from the central nervous system. A small amount of capsaicin must be applied to the area of inflammation about four times a day. During the first few days of use, the patient will experience a warm, stinging sensation when the cream is applied. This sensation goes away, and pain relief usually begins within 1 - 2 weeks.

Tramadol

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone with more long-lasting benefits than acetaminophen. Side effects are the same as for each of these drugs.

Narcotics

Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system, are the most powerful medications available for the management of moderate to severe pain. There are two types of narcotics:

• Opiates, which are derived from natural opium (morphine and codeine).
• Opioids, which are synthetic drugs. They include oxycodone (Percodan, Percocet, Roxicodone, Oxycontin), hydrocodone (Vicodin), oxymorphone (Numorphan), and fentanyl (Duragesic).

Although the use of narcotics for arthritic pain is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse. Some experts believe that opioids have a place in osteoarthritis treatment when milder drugs are not effective or appropriate. For example, a 2006 study suggested that a fentanyl skin patch may offer pain relief and improved function to some patients with severe knee or hip osteoarthritis who have not been helped by, or who cannot tolerate, NSAIDs or weaker opioids.

The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects. Common side effects include anxiety, constipation, nausea and vomiting, dizziness, drowsiness, paranoia, urinary retention, restlessness, and labored or slow breathing. Unfortunately, opioid abuse among young people is a major concern.

Corticosteroids

When pain becomes a major problem and less potent pain relievers are ineffective, doctors may resort to corticosteroid (steroid) injections, usually by administering a shot into the affected joint every 3 months. Corticosteroid shots are useful only if inflammation is present in the joint. Relief from pain and inflammation is of short duration, and this treatment is rarely used for chronic osteoarthritis. These drugs may not be as effective for women as for men.

Corticosteroids mask pain, and the patient must be very careful to avoid over-use of the affected joints. Patients are usually advised not to have more than two or three injections a year, since there is some concern that repeated injections over the long term may be harmful. A reassuring study found no greater disease progression in people who had injections every 3 months for 2 years compared to those who were given sham injections on the same schedule. Because long-term use of corticosteroids has many potentially serious side effects, steroid medications are never given orally or systemically for the treatment of osteoarthritis.

Hyaluronic Acid Injections (Viscosupplementation)

Injections of hyaluronic acid (Hyalgan, Synvisc, Artzal, Nuflexxa) into the joint -- a procedure called viscosupplementation -- is now recommended as one of the treatments for osteoarthritis. Hyaluronic acid is a naturally occurring substance in joints that acts as a lubricant for slow movements and a shock absorber for fast motions. In high amounts, it also may have anti-inflammatory effects.

• Patients receive a series of three to five injections once a week.
• The drug is injected into the joint.
• A health care worker will apply local anesthetic because these viscous (sticky) injections require a large needle.
• Patients need to avoid weight-bearing activities for about 48 hours after each shot.

Hyaluronic injections appear to be about as effective as NSAIDs and corticosteroid injections for relieving pain, at least in men, and they have no adverse effects in the stomach or intestines. One study reported that between 39 - 56% of patients were at least nearly free of weight-bearing pain up to 24 weeks after the final injection. In another study, response was judged better or much better for 87% of knees after a second course, which was administered about 8 months later. Nevertheless, a number of studies on viscosupplementation have shown little or no benefits, particularly in women, and more research is needed to determine if they are useful. Injections are also expensive. Accurate placement of the needle directly into the knee joint space is important and may be difficult, even for experienced doctors, if there is no fluid build-up in the joint. Best success rates are with a specific approach into the kneecap called the lateral midpatellar.

Side Effects. Serious adverse reactions are rare. The most common side effects, pain at the injection site and knee pain and swelling, are usually mild and temporary. More research is needed to confirm benefits and long-term risks.

Investigational Therapies

Researchers are studying various drugs that may provide pain relief or stop the disease process itself:

• Bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) help prevent bone loss in people with osteoporosis. They are currently being investigated for osteoarthritis as well. A 2005 study reported that risedronate may delay joint destruction in patients with knee osteoarthritis.
• Lidocaine, a local anesthetic, is available in patch form (Lidoderm) and has been used specifically for herpes zoster pain. Early studies indicate that it may provide significant pain relief for osteoarthritis.
• Tetracycline antibiotics, such as doxycycline, may have a role to play in treating osteoarthritis. At low concentrations, the drug reduces the production of collagenases, which are enzymes critical to disease development and progression. Initial results from clinical trials suggest that doxycycline may help delay joint space narrowing.
• Licofelone is a drug that inhibits both the COX enzyme plus an inflammatory substance called lipoxygenase 5. Early trials indicate it may be effective and safer than either NSAIDs or COX-2 inhibitors.
• Diacerein inhibits an inflammatory substance in arthritic joints called interleukin-1b. It has shown promise in clinical trials. A 2006 review indicated that diacerein may be slightly better than NSAIDs for pain relief.
• Botulinum toxin type A (Botox) injections may provide sustained pain relief for patients with knee osteoarthritis according to research presented at the 2006 American College of Rheumatology annual meeting.
• Nitric oxide increases blood flow in the mucous lining and secretions of mucus and bicarbonate. Combining nitric oxide with NSAIDs may reduce the adverse effects on the gastrointestinal tract.
• Trials of gene therapies that either fight joint degradation or strengthen cartilage are in very early stages.