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, Panadol, Phenaphen, Valadol, and others) is currently the first choice for treating osteoarthritis. Acetaminophen may be 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.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and the stimulation of red blood cell production.

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 available:

• Over-the-counter NSAIDs include aspirin, ibuprofen (such as Advil, Nuprin, Motrin IB, and Rufen), naproxen (such as Aleve and Naprosyn), ketoprofen (such as Actron and 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. Long-term use of NSAIDs does not actually delay the progression of osteoarthritis and may increase patients' risk of side effects. High dosages of NSAIDs can cause heart problems (such as increased blood pressure), kidney problems, and stomach bleeding.

Drug manufacturers of prescription and over-the-counter NSAIDs must now 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. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Both NSAIDs and COX-2 inhibitors are equally effective for pain relief and pose similar risks for heart attacks.

NSAID-Induced Ulcers and Gastrointestinal Bleeding

Long-term use of 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 or digestive tract bleeding, patients with serious heart conditions, alcohol abusers, and those on certain medications, such anticoagulants ("blood thinners"), corticosteroids, or bisphosphonates (drugs used for osteoporosis).

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-induced 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 diclofenac sodium/misoprostol (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 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.

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 (such as Percodan, Percocet, Roxicodone, and 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. Opioids may have a place in osteoarthritis treatment when milder drugs are not effective or appropriate.

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 try corticosteroid (steroid) injections, usually by giving the patient a shot in their 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 they are for men.

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 by mouth or systemically for the treatment of osteoarthritis.

Hyaluronic Acid Injections (Viscosupplementation)

Shots of hyaluronic acid (such as Hyalgan, Synvisc, Artzal, and Nuflexxa) into the joint -- a procedure called viscosupplementation -- are one of the recommended treatments for osteoarthritis. Hyaluronic acid is a naturally occurring substance in joints, which 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 shots spread a week apart.
• The doctor will first use a local anesthetic because these viscous (sticky) shots need a large needle.
• The drug is injected into the joint.
• 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 shots for relieving pain, at least in men, and they have no adverse effects in the stomach or intestines. While several studies have shown a benefit for this treatment, 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. The shots 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: The treatments below are still experimental, and may not be available to patients in the United States.

• 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.
• Tetracycline antibiotics, such as doxycycline, may have a role to play in treating osteoarthritis. Initial results from clinical trials suggest that doxycycline may help delay joint space narrowing. Its effects on osteoarthritis pain are less clear, and side effects of long-term treatment with tetracycline are unknown.
• Licofelone is a drug that inhibits both the COX enzyme plus an inflammatory substance called lipoxygenase 5. Early trials indicate it may be as effective, and safer, than either NSAIDs or COX-2 inhibitors. In addition to pain relief, licofelone may actually slow down the progression of osteoarthritis.
• Botulinum toxin type A (Botox) injections are being investigated for patients with knee osteoarthritis. However, no strong evidence to date supports its use.
• Clinical trials of gene therapies that either fight joint degradation or strengthen cartilage are in very early stages.