A meta-analysis of 30 randomized trials evaluating mindfulness meditation for chronic pain (5 trials in patients with OA or RA) found a moderate improvement in pain (standardized mean difference 0.32, result limited by significant heterogeneity) compared to standard care, passive controls, or education/support groups. 34
compared to placebo on a 0-10 scale was only 0.88 points. Physical function improved modestly. No SNRIs are FDA approved to treat OA. Anticonvulsants A small randomized controlled trial (RCT) of 89 patients with knee OA suggests pregabalin may reduce pain and improve function compared to the NSAID meloxicam, but the combination of meloxicam with pregabalin was better than either alone. 66 The study lasted four weeks, and longer-term RCT data are still needed. Pregabalin is not FDA approved for OA. Topical lidocaine A 12-week RCT of 143 patients with knee OA found that a lidocaine 5% patch had similar effects on OA pain and function as celecoxib 200 mg daily. 67 However, lidocaine patches are not FDA approved for the treatment of OA, and more data are needed to support their use. Other treatment options Glucosamine and chondroitin, either alone or in combination, do not provide long-term benefit in OA, but a small number of clinical trials demonstrated that maximum effects were achieved at 3-6 months. 68 Topical capsaicin gel reduced pain 53% from baseline compared to a 27% reduction with placebo in one 12-week study. In a review of 2 studies, redness and burning sensation was reported by 44% and 46% of patients, respectively, randomized to capsaicin. 69 A 2018 network meta-analysis of 28 trials, however found that topical capsaicin 0.025% four times daily and topical NSAIDs were equally effective for relieving pain in patients with knee or hand OA. 70 Intra-articular injections A number of injectable intra-articular agents are available to treat knee OA, with the two most-recently-approved being the synthetic corticosteroid triamcinolone acetonide extended release injection (Zilretta) and single-injection hyaluronic acid gel (Durolane). The evidence base for these treatments, however, is very weak, with effects frequently time-limited and study outcomes focused on cartilage and joint structure rather than pain and function. 68 A meta-analysis of 14 double- blind, sham-controlled trials with at least 60 patients in each trial found no clinically relevant differences between hyaluronic acid and sham injections. 71 Two randomized trials comparing single injection hyaluronic acid gel (Durolane) vs. placebo in a total of 564 patients with knee OA found no significant differences in pain, function, or joint stiffness at 6 weeks or 26 weeks. 72,73 OA is a common reason for joint replacement surgery. For older patients with functionally disabling chronic pain unresponsive to other therapies, surgery may provide relief.
Low back pain
Low back pain (LBP) is one of the most common reasons for physician visits in the U.S., and about 25% of U.S. adults reported having LBP lasting at least a day in the past three months. 74 Imaging is of limited utility in diagnosing the cause of LBP because most patients have nonspecific findings, and asymptomatic patients often have abnormal findings. Magnetic resonance imaging (MRI) is recommended for red flag symptoms (for example, incontinence or saddle anesthesia), radicular symptoms, or risks for pathologic fracture. 75 Current guidelines by the American College of Physicians recommend trying nonpharmacological options such as exercise, multidisciplinary rehabilitation, acupuncture, or yoga as first-line treatments for chronic low back pain, followed by pharmacologic treatment with an NSAID. 74 If the patient has an inadequate response, second-line options are a tricyclic antidepressant or duloxetine. Opioids, including tramadol, should be reserved for patients with pain unresponsive to all other treatments, with all of the caveats and cautions described previously 76 , although some experts in pain medicine assert that opioids should never be used to treat nonstructural low back pain. 77
Pharmacologic options
NSAIDs Given the inflammatory mechanism of OA, NSAIDs are the first-line pharmacologic option for managing OA-related chronic pain. In a network meta-analysis of 76 randomized trials evaluating oral celecoxib, ibuprofen, or naproxen vs. placebo in 58,451 patients with knee or hip OA, NSAIDs were associated with small-to-moderate effect sizes for improvements in pain and function, although results were not significant for naproxen at daily dose of 750 mg, or ibuprofen at daily dose of 1200 mg. 60 Topical vs. Oral NSAIDs Topical NSAIDs may be as effective as oral NSAIDs for OA pain. A randomized trial of 282 older patients with chronic knee pain comparing oral vs. topical ibuprofen found equivalent changes in the WOMAC OA index. 61 While side effects in the study did not vary between oral and topical NSAIDs, a small, statistically significant increase in serum creatinine was observed for oral NSAIDs. Generally, topical NSAIDs are considered safer due to a decreased systemic absorption. Topical NSAIDs may be recommended over oral NSAIDs for localized, single joint pain (e.g., knee OA). 62 Acetaminophen A 2019 Cochrane review of 10 randomized trials comparing acetaminophen vs. placebo in 3,541 patients with knee or hip OA found small, but not clinically important, reductions in pain and improvements in function with acetaminophen when used from between 3 weeks and 3 months. 63 These results should be interpreted cautiously, because daily acetaminophen doses of ~2,000 mg may not be effective over longer time frames (i.e., 3 months). The incidence of adverse events was similar between groups. 63 Generally, scheduled dosing is better than as-needed dosing for relief of chronic pain. The recommended starting dose of acetaminophen for elderly patients is 325 mg every 4 hours, with a maximum daily dose of 3000 mg. 62,64 SNRIs A meta-analysis of three trials of duloxetine for knee OA showed patients on duloxetine (60 or 120 mg daily) were 49% more likely to have a moderate pain response (≥30% reduction in pain intensity). 65 But the mean reduction in pain score with duloxetine
Non-drug options
Exercise In a review of 19 RCTs, exercise provided small reductions in pain compared to no exercise. Small, but not statistically significant, improvements in function were also observed. 35 Types and duration of exercise from RCTs included in the meta-analysis were not specified. Although physical therapy has a role in the management of acute low back pain, no RCTs of physical therapy were identified for chronic low back pain. Weight loss Only small, uncontrolled pilot studies suggest possible benefit from weight loss for patients with chronic low back pain. 78,79 After bariatric surgery, there was a 44% reduction in pain and a 26% improvement in function from a BMI reduction of 3 kg/m 2 (n=58). 79 Calorie restriction among obese patients suggests a reduction in pain and a significant improvement in function (n=46). 79 RCTs are needed to provide more conclusive evidence of Two trials (n=160 and n=320) found that tai chi modestly reduced pain versus wait list or no tai chi on a 0- to 10-point scale although these differences may not be clinically important. 80,81 The first trial randomized 160 adults with persistent non-specific low back pain to tai chi (18 sessions, 40 minutes each, over a 10-week period) vs. usual care. benefit. Tai Chi
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