Nontramadol Opioids Should Not Be Routinely Used for Osteoarthritis
By Laurie Barclay, MD
Medscape Medical News
October 19, 2009 — Nontramadol opioids should not be routinely used for osteoarthritis even if pain is severe, according to the results of a systematic review reported online in the October 7 issue of the Cochrane Database of Systematic Reviews.
"Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly," write Eveline Nuesch, from the University of Bern in Bern, Switzerland, and colleagues. "Opioids may be a viable treatment option if patients suffer from severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory."
The goal of this study was to compare oral or transdermal opioids vs placebo or no intervention in patients with osteoarthritis of the hip or knee, in effects on pain and function and safety. The reviewers searched CENTRAL, MEDLINE, EMBASE, and CINAHL (up to 28 July 2008), as well as conference proceedings and bibliographies of identified articles, and they contacted study authors for additional data when indicated.
Inclusion criteria were randomized or quasi-randomized controlled trials, without language restrictions, comparing oral or transdermal opioids other than tramadol vs placebo or no treatment in patients with knee or hip osteoarthritis. Data were extracted in duplicate and standardized mean differences (SMDs), and 95% confidence intervals (CI) were calculated for pain and function and risk ratios for safety outcomes. Inverse-variance random-effects meta-analysis was used to combine trials.
Of 10 trials included, enrolling a total of 2268 participants, 4 trials studied oral oxycodone, 3 trials studied oral codeine, 1 studied transdermal fentanyl, 1 studied oral morphine, and 2 studied oral oxymorphone. Compared with control interventions, opioids offered better 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). Efficacy did not vary markedly based on opioid type, analgesic potency, daily dose, duration of treatment or of follow up, methodologic quality of studies, or type of funding.
Compared with patients in control groups, those receiving opioids were more likely to have adverse events. For any adverse event, pooled risk ratio was 1.55 (95% CI, 1.41 - 1.70; 4 trials). Pooled risk ratios were 4.05 for study dropout because of adverse events (95% CI, 3.06 - 5.38; 10 trials) and 3.35 for serious adverse events (95% CI, 0.83 - 13.56; 2 trials). Stopping fentanyl treatment was associated with more severe withdrawal symptoms vs placebo (SMD, 0.60; 95% CI, 0.42 - 0.79; 1 trial).
"The small to moderate beneficial effects of non-tramadol opioids are outweighed by large increases in the risk of adverse events," the review authors write. "Non-tramadol opioids should therefore not be routinely used, even if osteoarthritic pain is severe."
Limitations of this study include funding of most of the trials by the pharmaceutical industry and inability to exclude potential publication bias.
"Clinicians are advised to use non-tramadol opioids cautiously and to consider alternatives, such as surgery," the review authors conclude. "In addition, clinicians should inform patients about the substantial risks and only moderate benefits of opioid treatment and therapeutic alternatives."
The Institute of Social and Preventive Medicine at the University of Bern and the Swiss National Science Foundation in Switzerland supported this study. The review authors have disclosed no relevant financial relationships.
Cochrane Database Syst Rev. Published online October 7, 2009.
