The best medicine for arthritis depends on which type you have. Osteoarthritis, the wear-and-tear kind, is typically managed with pain relievers and anti-inflammatory drugs. Rheumatoid arthritis, an autoimmune condition, requires medications that calm the immune system to prevent joint damage. Here’s what works for each type and what to know before choosing.
Over-the-Counter Options for Osteoarthritis
For mild to moderate osteoarthritis pain, acetaminophen (Tylenol) helps some people and is easy on the stomach. It won’t reduce inflammation, though, so if your joints are swollen, it may not be enough. The main safety concern is liver damage if you exceed the recommended dose, especially if you drink alcohol regularly.
NSAIDs like ibuprofen (Advil, Motrin) and naproxen (Aleve) are often more effective because they reduce both pain and inflammation. These are the go-to choice for most people with osteoarthritis. The tradeoff is that long-term use at high doses carries real risks. A large Oxford University analysis found that high-dose ibuprofen and diclofenac increase the risk of a major cardiovascular event (heart attack, stroke, or cardiovascular death) by about a third, translating to roughly 3 extra heart attacks per year for every 1,000 patients treated. They also raise the risk of stomach ulcer bleeding by two to four times, depending on the specific drug and dose.
If you only need occasional relief, these risks are small. But if you’re taking NSAIDs daily for months, the cumulative effect matters, particularly if you already have heart disease risk factors or a history of stomach problems.
Topical Pain Relievers
Topical NSAID gels offer a way to get anti-inflammatory relief with fewer whole-body side effects. Diclofenac gel (sold over the counter as Voltaren) is applied directly to the skin over the painful joint and can relieve pain about as well as oral NSAIDs for accessible joints like knees, hands, and elbows. Because less of the drug enters your bloodstream, the cardiovascular and stomach risks are lower.
The typical routine involves applying the gel four times a day. For a knee, that’s about 4 grams per application; for smaller joints like hands or wrists, about 2 grams. It works best on joints close to the skin surface. Deep joints like hips don’t absorb enough of the medication to make a meaningful difference.
Prescription Medications for Osteoarthritis
When over-the-counter options aren’t enough, doctors can prescribe stronger NSAIDs or other approaches. One option that surprises many people is duloxetine (Cymbalta), a medication originally developed as an antidepressant. It’s FDA-approved for chronic pain, including osteoarthritis pain, and works by changing how your brain processes pain signals. It can be especially useful when pain has become persistent and centralized, meaning your nervous system has become more sensitive to it over time.
Corticosteroid injections directly into the joint are another option for flare-ups. They provide fast, targeted relief that can last weeks to months. There are no firmly established yearly limits on how many injections you can receive, but guidelines suggest waiting at least two to three weeks between injections and stopping once you’ve gotten acceptable relief or the benefit plateaus. Most doctors space them out by several months to minimize any potential effect on cartilage.
Immune-Targeting Drugs for Rheumatoid Arthritis
Rheumatoid arthritis is fundamentally different from osteoarthritis. Your immune system attacks your own joint tissue, causing inflammation that progressively destroys cartilage and bone. Pain relievers alone won’t stop that damage. Treatment guidelines from the European Alliance of Associations for Rheumatology (EULAR) recommend starting disease-modifying drugs as soon as rheumatoid arthritis is diagnosed.
Methotrexate is the cornerstone first treatment. It broadly suppresses the overactive immune response driving joint destruction. Most people notice improvement within 6 to 8 weeks, though finding the right dose can take longer, sometimes 3 to 6 months of adjustments. If methotrexate isn’t tolerated, alternatives include leflunomide and sulfasalazine, which work through similar broad immune suppression. Hydroxychloroquine is another option, often used for milder disease.
The goal with these medications is remission or at least low disease activity. Doctors typically reassess every one to three months during active disease. If there’s no meaningful improvement within 3 months, or the target isn’t met by 6 months, the treatment plan gets adjusted.
Biologics and Advanced Therapies
When standard immune-suppressing drugs don’t control rheumatoid arthritis adequately, biologics are the next step. These are precision medications that block specific proteins driving inflammation rather than broadly suppressing the immune system.
The most established class targets a protein called TNF, which is a major trigger of inflammatory joint damage. Five TNF inhibitors are FDA-approved: infliximab, adalimumab, etanercept, golimumab, and certolizumab. These are given by injection or infusion and are used for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, among other conditions. They can dramatically reduce pain, swelling, and long-term joint damage in people who didn’t respond well to methotrexate alone.
JAK inhibitors (tofacitinib, baricitinib, upadacitinib) are newer oral medications that block specific signaling pathways inside immune cells. They’re effective, but the FDA now requires their strongest safety warning on these drugs after a large clinical trial found increased risks of heart attack, stroke, blood clots, cancer, and death with tofacitinib compared to TNF inhibitors. As a result, JAK inhibitors are now limited to patients who haven’t responded to or can’t tolerate TNF inhibitors. Risk factors that warrant extra caution include being over 65, smoking history, and existing cardiovascular risk factors.
Do Glucosamine and Chondroitin Work?
Glucosamine and chondroitin are among the most popular supplements for joint pain, but the evidence is genuinely mixed. A combined analysis of 29 studies with over 6,100 participants found that glucosamine and chondroitin each reduced knee osteoarthritis pain when taken separately, but not when combined. Individual study results were inconsistent, and the quality of the supplement matters: pharmaceutical-grade preparations showed better results than typical over-the-counter products.
Major arthritis organizations don’t agree on what to recommend. The American College of Rheumatology and the Osteoarthritis Research Society International both strongly recommend against glucosamine and chondroitin, citing weak or inconsistent evidence. The American Academy of Orthopaedic Surgeons takes a softer stance, listing both supplements as potentially helpful for mild to moderate knee osteoarthritis while acknowledging the evidence is inconsistent.
If you want to try them, pharmaceutical-grade versions appear more likely to help. But don’t rely on them as your primary treatment, especially if your pain is moderate or worsening. They’re unlikely to match the relief of NSAIDs or prescription options.
Choosing the Right Approach
For osteoarthritis, most people start with topical or oral NSAIDs and add other options as needed. Topical gels are a smart first choice for knee or hand arthritis since they deliver relief with less systemic risk. If you need oral NSAIDs regularly, using the lowest effective dose for the shortest time reduces cardiovascular and stomach complications.
For rheumatoid arthritis, early and aggressive treatment with methotrexate or similar drugs is critical. Joint damage that occurs in the first two years can be irreversible, so the priority is getting inflammation under control quickly rather than managing pain alone. Biologics and JAK inhibitors are reserved for cases where first-line drugs fall short, and the choice between them increasingly depends on your individual risk profile for heart disease and other conditions.