The most effective options for osteoarthritis pain are oral or topical anti-inflammatory drugs (NSAIDs), which improve both pain and joint function in the knee, hip, and hand. But the best choice depends on your symptoms, your stomach, your heart health, and how long you’ve been managing the condition. Here’s what works, what’s questionable, and what to skip.
Topical NSAIDs: The Best Starting Point for Knee Pain
If your osteoarthritis is in your knee, a topical NSAID gel or cream is one of the smartest first moves. Topical formulations deliver pain relief comparable to oral NSAIDs in meta-analyses, but only about 5% of the drug enters your bloodstream. That dramatically lowers your risk of stomach and intestinal problems. One study found that switching from oral to topical NSAIDs reduced severe gastrointestinal side effects from 26% to 17%.
The trade-off is minor: topical NSAIDs can cause dry skin and itching at the application site. About 1 in 7 people experience some form of local skin reaction. Topical diclofenac is the most widely available option and comes in both prescription and over-the-counter strengths. These work best for joints close to the skin surface, which is why they’re recommended for knees and hands but not as practical for deeper joints like hips.
Oral NSAIDs: Effective but Use With Caution
Oral NSAIDs like ibuprofen, naproxen, and celecoxib are the workhorses of osteoarthritis treatment. They reliably reduce pain and improve function in knee, hip, and hand arthritis. The American College of Rheumatology recommends using the lowest effective dose for the shortest time you can manage, because these drugs carry real risks with long-term use: stomach ulcers, kidney strain, and cardiovascular complications.
You should avoid oral NSAIDs if you have kidney problems, active stomach ulcers, or are at elevated risk of heart attack or stroke. People on blood thinners also need to be careful. Celecoxib is gentler on the stomach than older NSAIDs but carries its own cardiovascular warnings and should not be used during pregnancy. For many people, alternating between topical and occasional oral NSAIDs strikes the right balance between relief and safety.
Acetaminophen: Mild Relief at Best
Acetaminophen (Tylenol) has long been recommended as a safer alternative to NSAIDs, but the evidence is underwhelming. A meta-analysis of 10 randomized trials involving over 1,700 patients found that acetaminophen’s pain-relieving effect for osteoarthritis is statistically significant but small. In practical terms, most people notice only modest improvement compared to a placebo.
That said, acetaminophen remains an option for people who can’t tolerate NSAIDs due to stomach, kidney, or heart concerns. It’s not useless, just not powerful. If you rely on it, stay within the daily limit (typically 3,000 mg for most adults) to protect your liver, especially if you drink alcohol.
Duloxetine: A Non-Obvious Option That Works
Duloxetine is an antidepressant that also has FDA approval for chronic musculoskeletal pain, including osteoarthritis. It works by changing how your brain processes pain signals, which makes it a completely different approach from anti-inflammatory drugs. The ACR guidelines include it as a reasonable option for people who haven’t gotten enough relief from NSAIDs alone.
The typical dose is 60 mg once daily, usually started at 30 mg for the first week so your body can adjust. The most common side effects are nausea, dry mouth, fatigue, constipation, drowsiness, and dizziness. These tend to be most noticeable in the first few weeks. Duloxetine can be especially useful if your osteoarthritis pain is accompanied by depression or anxiety, since it addresses both.
Corticosteroid Injections: Fast but Temporary
Steroid injections directly into the joint provide short-term improvement in pain and function for knee and hip osteoarthritis. They work fast, typically within days, and deliver the strongest relief in the first month. By three months, though, the benefit fades, and most people are back to baseline within a few months.
These injections are best used as a bridge during flare-ups rather than as ongoing treatment. Repeated steroid injections over time may contribute to cartilage thinning, so most doctors limit them to a few per year per joint. If you need something longer-lasting, hyaluronic acid injections are an alternative that takes longer to kick in but may provide relief lasting up to six months, outperforming steroids at that time point. However, the ACR guidelines actually recommend against hyaluronic acid based on inconsistent evidence, so this remains a judgment call between you and your doctor.
Glucosamine and Chondroitin: Likely a Waste of Money
Glucosamine and chondroitin are among the most popular supplements marketed for joint health, but the independent evidence is not encouraging. The ACR specifically recommends against them because studies without industry funding have consistently failed to show meaningful benefit. A major U.S. trial following 572 participants over two years found that glucosamine, chondroitin, and the combination of both did not slow cartilage loss any more than a placebo.
Some people swear by these supplements, and the placebo response in arthritis trials is genuinely strong. If you’ve been taking them and feel better, there’s little harm in continuing since they’re generally safe. But if you’re deciding whether to start, the clinical evidence says your money is better spent elsewhere.
Curcumin: Promising but Unproven
Curcumin, the active compound in turmeric, has generated real interest for osteoarthritis. In one trial of 139 people with moderate-to-severe knee osteoarthritis, curcumin (500 mg three times daily) performed nearly as well as the prescription NSAID diclofenac over one month: 94% of curcumin users reported at least 50% improvement compared to 97% on diclofenac.
That sounds impressive, but the study had significant limitations. It was small, lasted only a month, looked at only knee osteoarthritis, and participants knew which treatment they were getting, which can skew results. Curcumin supplements also aren’t regulated like prescription drugs, so purity and potency vary widely between brands. If you want to try it, look for formulations designed for better absorption (standard curcumin is poorly absorbed on its own) and treat it as an addition to your plan rather than a replacement for proven treatments.
What to Avoid
Opioid painkillers other than tramadol are explicitly recommended against for osteoarthritis. The risk of dependency and side effects is high, and there’s no evidence they work better than safer options for this type of chronic pain. Tramadol itself is only recommended for select patients and is not a first-line choice.
Platelet-rich plasma (PRP) and stem cell injections are heavily marketed for joint pain but have not demonstrated consistent clinical benefit in rigorous trials, and both carry safety concerns. The ACR recommends against both. Similarly, nerve growth factor inhibitors (a class of injectable biologics that generated excitement a few years ago) have been held back by serious safety signals, including rapidly progressive joint destruction in a small percentage of patients. The FDA has not approved them.
Putting a Plan Together
For most people with osteoarthritis, a practical approach looks like this: start with a topical NSAID for accessible joints like knees and hands. Add oral NSAIDs at the lowest effective dose during flare-ups. Consider duloxetine if pain is persistent and NSAIDs aren’t enough or aren’t safe for you. Use steroid injections sparingly for acute flares. Layer in non-drug strategies like exercise, weight management, and physical therapy, which consistently show benefit in clinical guidelines and work synergistically with medication.
Osteoarthritis is a long game. The goal isn’t eliminating pain entirely but finding the combination that keeps you functional with the fewest side effects over months and years.