Medications treat OA when non-drug methods do not provide adequate relief. Previous guidelines touted acetaminophen (Tylenol) as a first-line agent, primarily due to its lack of negative side effects (compared to nonsteroidal anti-inflammatory medications [NSAIDs]). However, more recent guidelines refute this recommendation.
Acetaminophen has fallen out of favor as an agent in OA due to its minimal effectiveness. A recent systematic review showed that acetaminophen is slightly better than a placebo in treating (managing pain and improving function) knee or hip OA. Still, the improvement is not clinically significant (Leopoldino et al., 2019). The research also suggested that acetaminophen is more likely to lead to liver function abnormalities. Liver injury is more common with prolonged use of acetaminophen in higher than recommended doses or when combined with alcohol or certain medicines such as statins (e.g., atorvastatin, simvastatin).
The American Academy of Orthopaedic Surgeons (AAOS) recommends using acetaminophen if it improves pain and function. Caution should be used in patients who are on warfarin. Combining acetaminophen and warfarin can increase the international normalized ratio (INR). Absolute contraindications to acetaminophen include liver failure, while relative contraindications include chronic alcohol abuse or hepatic insufficiency (AAOS, 2021).
Others recommend acetaminophen as the least effective option compared to NSAIDs or the combination of glucosamine and chondroitin (Zhu et al., 2018). Research acknowledges that acetaminophen's side effect profile is less toxic than NSAIDs. NSAIDs are considered more effective than acetaminophen in relieving hip and knee pain in OA (Lozada, 2022). Like acetaminophen, NSAIDs act synergistically with opioids.
NSAIDs, such as ibuprofen (Motrin, Advil), naproxen sodium (Aleve, Naprosyn), choline and magnesium salicylates (Trilisate), diclofenac sodium (Voltaren, Voltaren XR), celecoxib (Celebrex), meloxicam (Mobic), and nabumetone (Relafen), are recommended over acetaminophen (Kolasinski et al., 2020). These medications have more side effects than acetaminophen, including hypertension, edema, gastrointestinal bleeding, dyspepsia, headaches, constipation, mental status changes, and renal insufficiency/kidney failure.
Absolute contraindications to NSAIDs include chronic kidney disease, an active peptic ulcer, and heart failure. Relative contraindications include a Helicobacter pylori infection, a history of peptic ulcer disease, hypertension, or concomitant use of selective serotonin receptor inhibitors or corticosteroids. NSAIDs may interact with aspirin, warfarin, antihypertensive medications, selective serotonin reuptake inhibitors, and corticosteroids.
Risk factors for gastric ulceration include older age, current use of corticosteroids, bleeding problems, or a history of gastric ulceration. These individuals should likely not use NSAIDs. The use of a proton pump inhibitor or misoprostol reduces the risk of gastric ulceration with the use of NSAIDs.
Another option for those with a risk for gastric ulceration is using celecoxib. Celecoxib is the only available selective inhibitor of cyclooxygenase-2 (COX-2), and COX-2 inhibitors are less likely to lead to gastric irritation. A COX-2 agent and a proton pump inhibitor can be used in those at high risk of gastrointestinal bleeding. Monitoring for and eradicating Helicobacter pylori reduces the risk of NSAID-induced gastrointestinal injury.
NSAIDs can potentially cause nephrotoxicity because they inhibit prostaglandin synthesis, which is associated with vasoconstriction of the afferent arteriole in the kidney and may lead to renal impairment. Compared to traditional NSAIDs, celecoxib has a lower risk of GI bleeding (Shin, 2018).
NSAIDs are associated with cardiovascular complications. They interfere with the cardioprotective effect of aspirin, elevate blood pressure, and may precipitate or aggravate heart failure. NSAIDs may also amplify the risk of clotting and should be used cautiously in those with a history of venous thrombosis. They should also be avoided in those with thrombocytopenia.
Generally, NSAIDs are equally effective. However, if one agent is ineffective, another NSAID may be effective, as there is individual variation in response to different NSAIDs. A recent meta-analysis showed that etoricoxib 60 mg/day and diclofenac 150 mg/day reduce pain and improve function in OA more than other agents but are associated with more adverse events (Da Costa et al., 2021).
Topical NSAIDs should be first-line agents as they demonstrate similar effectiveness to oral NSAIDs without systemic side effects (Klinge & Sawyer, 2013). They are especially helpful if the disease is localized to one area. In the United States, diclofenac sodium topical gel and diclofenac sodium topical solution are available to manage OA.
Other topical agents can provide significant relief for patients with OA. Capsaicin (Zostrix) decreases the neurotransmitter called substance P, which transmits pain. Capsaicin is applied three to four times a day, and it takes capsaicin a few weeks before it provides significant pain relief. Hands should be washed after contact with the substance. Kolasinski et al. (2020) suggest topical capsaicin be conditionally recommended in those with OA of the knee but not recommended in those with hand OA. The use of capsaicin in the hip is not likely to be helpful.
Another topical agent sometimes used to treat localized pain is the lidocaine patch. The Food and Drug Administration does not approve this patch for use in OA, but it is often used. It is a small patch applied to the skin around the painful joint and worn for no more than 12 hours daily.
The central nervous system (CNS) is involved in the pain of OA, so some medications address pain originating from the CNS. CNS medications that may be useful in treating OA include gabapentin and duloxetine. Gabapentin demonstrates limited efficacy in those with knee OA (Katz et al., 2021). Duloxetine is sometimes tried in those who do not respond to or have contraindications to NSAIDs. Research has shown that these agents improve function and reduce pain but is associated with significant side effects, including fatigue, dry mouth, constipation, decreased appetite, and nausea (Osani & Bannuru, 2019).
Tramadol (Ultram®, Ultram® ER) is dosed 50-100 mg every 4-6 hours for the immediate-release form and 100 mg daily for the extended-release form. For individuals suffering from chronic arthritic pain, the immediate release is initiated at 25 mg in the morning and increased by 25-50 mg daily every three days. The maximum dose for the immediate-release form is 400 mg per day. The extended-release form starts at 100 mg once a day and increases by 100 mg every five days with a maximum dose of 300 mg daily. Side effects include constipation, dizziness, nausea, vomiting, euphoria, headache, itching, agitation, somnolence, hallucinations, and anxiety.
Tramadol interacts with narcotic medications and many antidepressants. It should be used carefully for those with moderate to severe renal or liver insufficiency. Tramadol lowers the seizure threshold and should be used cautiously in those with a history of seizures. Caution must be used with tramadol as it has abuse potential.
Narcotic medicines are used when pain cannot be controlled by other means. They should only be used on a time-limited basis in those with disabling symptoms or severe pain that have not responded to other treatment modalities. Before starting opioid therapy, it is important to determine the pain's effect on the patient's life, including functional ability and psychological impact. Narcotics are more powerful pain medications but have side effects. Narcotics have side effects of sedation, respiratory depression, dizziness, falls, constipation, addiction, and dependence. Narcotic medications include codeine, hydrocodone, hydromorphone, oxycodone, fentanyl, and morphine.