NSAIDs
We recommend nonsteroidal anti-inflammatory drugs (NSAIDs; oral or topical) or Tramadol for patients with symptomatic osteoarthritis of the knee.

Rationale
This recommendation included studies of both selective (cyclo-oxygenase-2, COX-2 inhibitors) and non-selective NSAIDs. The endorsement for NSAIDs was based on 202 favorable outcomes from 19 studies comparing either the selective, non-selective or topical analgesics to placebo. Twelve studies were of selective NSAIDs, four were of non-selective oral NSAIDs, and six were of topical NSAIDs. (Three studies compared multiple types of analgesics to placebo.) Three were high-strength studies, 14 were moderate, and two were of low-strength. The moderate and low strength studies were included because they examined different outcomes than the high strength articles. Out of 202 total outcomes, 171 were statistically significant in favor of the experimental group. Fifteen outcomes were above the MCII threshold and 63 outcomes were possibly clinically significant. The remaining outcomes were neither statistically nor clinically significant.
 
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.