Study Questions Combining Analgesics for Knee Pain

This cautious and excellent long-term study reveals many new and important findings that should be the basis for reconsidering treatment of musculoskeletal conditions with OTC analgesics. It may turn out that many of our widely held beliefs are wrong and that recommendations for our patients need to be changed.

The results indicate that we should reconsider the use of a combination of analgesics and also the use of paracetamol alone, as it is not sufficiently effective yet causes many unwanted effects including dyspepsia, diarrhea, and GI blood loss. In line with this notion, studies published during the past few years have shown that paracetamol increases blood pressure when taken for short or prolonged periods and augments the risk of major cardiovascular events when administered at high frequency or dose.

Moreover, there is no mechanistic justification for the combination of paracetamol with another cyclooxygenase-2 inhibitor: The enzyme responsible for the formation of algesic prostaglandin E₂ can only be blocked once. Two blockers cannot achieve more effects than one blocker! The analgesic action increases only marginally (if at all), but the unwanted drug effects increase substantially.

On the basis of this study, one wonders why combinations of analgesics of the type described and investigated here should remain on the OTC market. Obviously, there is no scientific evidence that either claim (higher efficacy and/or less toxicity) can be substantiated; rather, the contrary is true.

Kay Brune, M.D., is with the department of experimental and clinical pharmacology and toxicology at Friedrich-Alexander-University of Erlangen-Nuremberg (Germany). Burkhard Hinz, Ph.D., is with the Institute of Toxicology and Pharmacology at the University of Rostock (Germany). This was adapted from an editorial that accompanied the study (Ann. Rheum. Dis. 2011;70:1521-2).