Cochrane for Clinicians
Putting Evidence into Practice
Opioids for Osteoarthritis of the Knee or Hip
Am Fam Physician. 2010 May 1;81(9):1094-1096.
A 65-year-old woman who is obese has severe osteoarthritis of the knee and has not been able to tolerate nonsteroidal anti-inflammatory drugs (NSAIDs). She is seeking opioids for her debilitating pain.
Are opioids (oral or transdermal) an appropriate choice for treatment of patients with painful osteoarthritis?
Compared with placebo, the benefits achieved from opioid therapy are modest in terms of pain relief and improvement in function, and do not outweigh the increase in adverse effects. No single opioid stands out as more effective or safer than the rest.1 (Strength of Recommendation = A, based on consistent, good-quality patient-oriented evidence)
Chronic pain is reaching epidemic proportions in the United States.2 Hydrocodone (Hycodan) has become the most prescribed medication nationally.3 In the past, opioid use was limited primarily to acute pain and chronic cancer pain; currently, opioids are more liberally prescribed for other chronic noncancer pain syndromes.
The authors of this Cochrane review ask whether opioid therapy (not including tramadol [Ultram]) improves pain and function in a subset of patients with osteoarthritis of the knee or hip. Ten outpatient trials involving 2,268 participants were analyzed and included a variety of commonly used opioids.1 The median daily dose of morphine equivalency was 51 mg (considered low by the authors), and study duration ranged from three days to three months. In the treatment group, 35 percent of patients had a treatment response (i.e., a reduction of at least one half of their pain) versus 31 percent of patients in the control group (number needed to treat [NNT] = 25). Such gains were offset by adverse effects, although major adverse effects were rare. Furthermore, no one opioid emerged superior to another.
Given the increasing number of patients with chronic pain, family physicians should consider therapies supported by the Osteoarthritis Research Society International (OARSI) guidelines for osteoarthritis.4 Therapies include weight loss; acetaminophen; NSAIDs for short periods of time; topical NSAIDs or capsaicin (Zostrix); injections; glucosamine; acupuncture; exercise; thermal modalities; and, when necessary, joint replacement. The OARSI recommends using weaker opioids, such as codeine and tramadol. The Cochrane review showed codeine to be as effective and no more dangerous or intolerable than other opioids.1 A separate Cochrane review of tramadol alone showed a fairly robust treatment response with tramadol (NNT = 6; 95% confidence interval [CI], 4 to 9).5 However, considerably more participants taking opioids in this meta-analysis discontinued treatment because of major adverse effects (number needed to harm = 8; 95% CI, 7 to 12).5
This review brings up the larger issue of prescribing opioids for nonmalignant chronic pain.1 Prescription opioid abuse is estimated at 5 percent in the general population.6 Fatal poisonings from prescription opioids have nearly doubled in the past decade.7
Pain is a complex mind-body experience. In addition to pharmacologic therapy, physicians can take steps to improve a patient's overall well-being by addressing comorbid psychosocial issues, allowing adequate time for visits, and setting realistic expectations with patients on the limited benefits of opioids. Pain will likely persist; the goal of therapy should be improving function.2 The Federation of State Medical Boards provides functional assessment tools for controlled substance prescribing and pain management at http://www.fsmb.org/PAIN/resource.html#pain.
Background: Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older persons. Opioids may be a viable treatment option if patients have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory.
Objectives: To determine the effects on pain and function and the safety of oral or transdermal opioids as compared with placebo or no intervention in patients with osteoarthritis of the hip or knee.
Search Strategy: We searched CENTRAL, Medline, EMBASE, and CINAHL (up to July 28, 2008), checked conference proceedings and reference lists, and contacted authors.
Selection Criteria: Studies were included if they were randomized or quasirandomized controlled trials that compared oral or transdermal opioids with placebo or no treatment in patients with osteoarthritis of the knee or hip. Studies of tramadol were excluded. No language restrictions were applied.
Data Collection and Analysis: We extracted data in duplicate. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for pain and function, as were risk ratios for safety outcomes. Trials were combined using inverse-variance random-effects meta-analysis.
Main Results: Ten trials with 2,268 participants were included. Oral codeine was studied in three trials, transdermal fentanyl and oral morphine in one trial each, oral oxycodone in four, and oral oxymorphone in two trials. Overall, opioids were more effective than control interventions in terms of pain relief (SMD = −0.36; 95% CI, −0.47 to −0.26) and improvement of function (SMD = −0.33; 95% CI, −0.45 to −0.21). We did not find substantial differences in effects according to type of opioid, analgesic potency (strong or weak), daily dose, duration of treatment or follow-up, methodological quality of trials, and type of funding. Adverse events were more frequent in patients receiving opioids compared with control. The pooled risk ratio was 1.55 (95% CI, 1.41 to 1.70) for any adverse event (four trials), 4.05 (95% CI, 3.06 to 5.38) for dropouts due to adverse events (10 trials), and 3.35 (95% CI, 0.83 to 13.56) for serious adverse events (two trials). Withdrawal symptoms were more severe after fentanyl treatment compared with placebo (SMD = 0.60; 95% CI, 0.42 to 0.79; one trial).
Authors' Conclusions: The small to moderate beneficial effects of nontramadol opioids are outweighed by large increases in the risk of adverse events. Nontramadol opioids should therefore not be routinely used, even if osteoarthritic pain is severe.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org).
Physicians should consider routinely invoking pain agreements at the start of therapy.2,8 This can help delineate expectations, address important risks and benefits, and provide physicians with an opportunity to taper patients off of opioids when they are causing more harm than good. A sample pain agreement from the American Academy of Pain Medicine is available at http://www.painmed.org/pdf/controlled_substances_sample_agrmt.pdf. In addition, the American Pain Society has published consensus guidelines with risk assessment and monitoring tools in the appendices, one of which is available at http://download.journals.elsevierhealth.com/pdfs/journals/1526-5900/PIIS1526590008008316.pdf.8
It is also important to monitor patients for opioid abuse or diversion.2,8 A few states have online programs to obtain controlled prescription reports on patients during real-time patient visits (in California, for example: https://pmp.doj.ca.gov/pmpreg/RegistrationType_input.action). Such monitoring is more efficient than traditional methods of calling pharmacies or other offices of health care professionals. Urine toxicology testing can screen for use of illicit substances and, if the detection level is low enough, can also confirm that patients are actually taking some of their medication and not diverting all of it.
1. Nüesch E, Rutjes AW, Husni E, Welch V, Jüni P. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009;(4):CD003115.
2. Fishman SM. Responsible Opioid Prescribing: A Physician’s Guide. Washington, DC: Waterford Life Sciences; 2007.
3. Marketing Charts. U.S. prescription drug sales grow slowly; hydrocodone most prescribed. March 26, 2009. http://seekingalpha.com/article/128003-u-s-prescription-drug-sales-grow-slowly-hydrocodone-most-prescribed. Accessed January 29, 2010.
4. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–162.
5. Cepeda MS, Camargo F, Zea C, Valencia L. Tramadol for osteoarthritis. Cochrane Database Syst Rev. 2006;(3):CD005522.
6. Substance Abuse and Mental Health Services Administration, Office of Applied Studies. The NSDUH report: patterns and trends in nonmedical prescription pain reliever use: 2002 to 2005. April 6, 2007. Rockville, Md. DHSS publication no. (SMA) 06–4194. http://www.oas.samhsa.gov/2k7/pain/pain.htm. Accessed January 29, 2010.
7. Centers for Disease Control and Prevention. Overdose deaths involving prescription opioids among Medicaid enrollees—Washington, 2004–2007. MMWR Morb Mortal Wkly Rep. 2009;58(42):1171–1175.
8. Chou R, Fanciullo GJ, Fine PG, et al. American Pain Society–American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10(2):113–130.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Drs. Hitzeman and Athale present a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en/ab003115.html.
The series coordinator for AFP is Clarissa Kripke, MD, Department of Family and Community Medicine, University of California, San Francisco.
A collection of Cochrane for Clinicians published in AFP is available at http://www.aafp.org/afp/cochrane.
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