Do You Use Opioids in Your Patients with Rheumatoid Arthritis?

Michael R. Clark, MD, MPH

The risks are proven. The benefits are questionable. The alternatives are numerous. So is it ever a good idea to prescribe opioids for patients suffering with chronic pain from rheumatoid arthritis?

Several published guidelines say that there is a place for the use of opioid therapy for pain associated with rheumatoid arthritis (RA), but not as first-line treatment. The authors of “Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain,” published by the American Pain Society, stated that opioid therapy “generally would not be appropriate before a trial of… a disease-modifying antirheumatic drug for rheumatoid arthritis” (http://bit.ly/LFNOP5). Other guidelines recommend considering opioids when NSAIDs are contraindicated or poorly tolerated (http://bit.ly/MG9VF5).

“If you have tried everything else and serious pain persists, then opioids are certainly worth a try,” says Michael R. Clark, MD, MPH, Director of Chronic Pain Treatment Programs for Johns Hopkins Medical Institutions. “But if opioids are option two or three, then you’re exposing your patients to very serious risks and, quite likely, condemning them to inferior pain management.”

In addition to the much-discussed risks of opioid abuse, misuse, and diversion (http://bit.ly/MGgrM9), opioids are also associated with several potentially serious side effects even when used as prescribed, including nausea, vomiting, dizziness, constipation and, for some patients, impaired cognition and energy.

As for the benefits of opioid therapy, in 2011 investigators searched The Cochrane Library and other databases and identified 11 trials that compared opioids to other therapies in terms of adverse effects and effect on pain, function, and quality of life in patients with RA. The data showed that weak opioids may provide better short-term relief of RA pain than placebo, but may be associated with more side effects. The authors concluded that “there is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications” (http://bit.ly/MZsiAH). They also noted the absence of studies that looked at the effects of weak opioids taken for more than six weeks, as well as the lack of enough studies of strong opioids to enable them “to draw conclusions about their effects in rheumatoid arthritis.”

Fortunately for physicians and patients, there are other options beyond opioids for treating RA pain. One option is to pair one of the NSAIDs with a steroid. Should that approach fail to produce adequate analgesia, many doctors are often tempted to add another type of medication, but some experts advise patience. Each NSAID basically works in the same way, as does each steroid, but individual patients can have very different responses to similar medications, so doctors are advised try to find the best NSAID and the best steroid for each patient before adding additional agents.

"If you have tried everything else and serious pain persists, then opioids are certainly worth a try."

—Michael R. Clark, MD, MPH Director of Chronic Pain Treatment Programs for Johns Hopkins Medical Institutions

The next step might be to try an antidepressant. As with opioids, there isn’t much clinical evidence that antidepressant help RA pain (http://bit.ly/MZszDT). However, the anecdotal evidence appears promising, the side effects are relatively minor, and because chronic pain is a risk factor for depression (which can in turn exacerbate chronic pain symptoms), the logic makes sense. Antidepressants can help break this cycle, improve mood, and help relieve pain.

If this approach still fails to provide sufficient pain relief, it may be time to start again at the beginning. “If serious pain persists after that, forget pain medications and reconsider how you’re treating the underlying condition. Make sure the patient is taking everything properly. Try different medications or different dosages,” says Roy Fleischmann, MD, MACR, Clinical Professor of Medicine at UTSWMC and Medical Director, Metroplex Clinical Research Center. “Pain is often a sign that you haven’t got the disease under control.”

Opioids are an option

If nothing else works, or a patient’s medical problems rule out NSAIDs or steroids or both, then it may well be time to give opioids a try. Clark notes that studies have shown opioids to be effective in treating chronic nonmalignant pain such as low back pain and postherpetic neuralgia. Other studies have found opioid receptors in the peripheral tissues activated by inflammation, which indicates opioids might ameliorate inflammatory diseases like RA. Because there are no studies that have compared the merits of different opioids for RA, doctors must choose by logic and analogy.

Fleischmann starts RA patients with tramadol and, if necessary, moves to strong opioids. Clark says that he thinks less in terms of “weak” and “strong” and more about shortacting and long-acting. He recommends longacting opioids—multi-day patches, ideally— for three reasons: consistent pain relief, less tolerance risk, and lower abuse potential.

“The benefits of opioids are disappointingly small and the drawbacks are disappointingly large,” Fleischmann says, “but they do provide some genuine relief to some of my RA patients. They have a legitimate place in RA care. It’s just a very small place.”