Two high- and three moderate- strength studies examining the various outcome measures in this recommendation compared tramadol to placebo. They included outcome measurements with follow up periods that ranged from 8 to 13 weeks in duration. Ten of 14 outcomes were statistically significant in favor of the treatment group. Two statistically significant outcomes (WOMAC pain and stiffness subscale scores) were possibly clinically significant and the other eight outcomes could not be evaluated. Fishman et al.95 did not find any statistically significant improvements in pain efficacy between tramadol contramid doses of 100mg, 200mg and 300mg. Beaulieu et al.96 found similar treatment effects in tramadol and diclofenac in using WOMAC pain, stiffness and function subscale scales.
The recommendation on acetaminophen was downgraded from level B (i.e. Moderate) in the 2008 edition of the guideline to inconclusive in our current guideline. As opposed to the selection criteria previously used, our current systematic review examined acetaminophen separately and found only one relevant study that tested it against placebo (Miceli-Richard et al.97). Their study found no statistical significance or minimum clinically important improvement to patients compared to placebo. In addition, their findings and the previous clinical guideline were based on the usage of a maximum of 4000 mg of acetaminophen per day, and there has been a recent change to a dosage not to exceed 3000 mg per day; see: FDA Acetaminophen Dosage Announcement.
The work group realizes that many practitioners prefer to start with acetaminophen prior to NSAIDs due to the side effect profile of NSAIDs. However, we found it unreasonable to recommend a treatment that does not show benefit over placebo.
Our literature review found no relevant studies meeting our inclusion criteria on opioids or pain patches for the treatment of knee osteoarthritis.
- (95) Fishman RL, Kistler CJ, Ellerbusch MT et al. Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD). J Opioid Manag 2007;3(5):273-280. PM:18181382
- (96) Beaulieu AD, Peloso PM, Haraoui B et al. Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized controlled trial. Pain Res Manag 2008;13(2):103-110. PM:18443672
- (97) Miceli-Richard C, Le BM, Schmidely N, Dougados M. Paracetamol in osteoarthritis of the knee. Ann Rheum Dis 2004;63(8):923-930. PM:15249319
- (98) Schnitzer TJ, Weaver AL, Polis AB, Petruschke RA, Geba GP. Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies. J Rheumatol 2005;32(6):1093-1105. PM:15940774
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- Batlle-Gualda E,Roman IJ,Martin-Mola E,Carbonell AJ,Linares Ferrando LF,Tornero MJ,Raber BA,Fortea BJ. Aceclofenac versus Paracetamol in the management of symptomatic osteoarthritis of the knee: a double-blind 6-week randomized controlled trial. Osteoarthritis Cartilage 2007;15(8):900-908.
- Bradley JD,Brandt KD,Katz BP,Kalasinski LA,Ryan SI. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and Acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991;325(2):87-91.
- Schnitzer TJ,Tesser JR,Cooper KM,Altman RD. A 4-week randomized study of Acetaminophen extended-release versus Rofecoxib in knee osteoarthritis. Osteoarthritis Cartilage 2009;17(1):1-7.