The first randomized placebo-controlled trial of paracetamol (acetaminophen) for patients with acute low back pain has shown no effect of the drug on speed of recovery, pain, or many other factors associated with the condition.
“The results suggest we need to reconsider the universal recommendation to provide paracetamol as a first-line treatment for low-back pain,” lead author, Christopher Williams, PhD, the George Institute for Global Health at the University of Sydney in Australia, commented.
The Paracetamol for Low-Back Pain Study (PACE) was published online in The Lancet on July 24.
The authors conclude: “PACE provides high-quality evidence that, in addition to advice and reassurance, neither regular nor as-needed paracetamol significantly speed recovery from acute low-back pain.” In addition, “paracetamol had no effect on pain, disability, function, global symptom change, sleep quality, or quality of life.”
Noting that several other trials have found no difference between paracetamol and other simple analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in the management of acute lower back pain, the authors conclude: “Our findings…suggest that simple analgesics such as paracetamol might not be important in the management of acute low-back pain.”
Advice and Reassurance Best?
They point out that both treated and placebo PACE patients recovered at a faster rate than that typically reported in other studies of patients with acute back pain receiving miscellaneous or usual treatments.
They suggest a possible explanation for this could have been the good-quality advice and reassurance provided, a feature that is often absent from usual care. They therefore recommend that “advice and reassurance, rather than analgesics, should be the focus of first-line care.”
For the study, 1652 patients with acute low back pain were randomly assigned to receive paracetamol in regular doses (3 times per day; equivalent to 3990 mg paracetamol per day), as-needed doses of paracetamol (taken when needed for pain relief; maximum 4000 mg paracetamol per day), or placebo.
The primary outcome was time until recovery from low back pain, with recovery defined as a pain score of 0 or 1 (on a 0 to 10 pain scale) sustained for 7 consecutive days.
Median time to recovery was 17 days in the regular and as-needed paracetamol groups and 16 days in the placebo group. No differences were recorded in secondary outcomes of pain intensity, disability, symptom change, and function between the 3 study groups.
Substantial Effect on Practice
In an accompanying “Comment”, Bart W. Koes, MD, and Wendy T. Enthoven, MD, from University Medical Center, Rotterdam, the Netherlands, say the “well-designed” PACE trial could have a substantial effect on the management of patients with low back pain.
They note that worldwide, national clinical guidelines recommend paracetamol as the first-choice prescribed analgesic for acute low back pain, but because of a lack of sound clinical evidence, these recommendations have been based on indirect evidence from other pain specialties, consensus in guideline committees, and the relatively favorable safety profile of paracetamol compared with that of NSAIDs.
They suggest, however, that the guidelines should not be changed on the basis of a single trial, saying that “more robust and consistent evidence, including verification of the results in other populations, is needed.”
But Dr. Koes and Dr. Enthoven add that physicians and patients ought now to be aware that paracetamol might not be more effective than placebo in the treatment of acute low -back pain, and this could very well affect the decision of whether to start paracetamol.
They also point out that NSAIDs, which are the next choice in the guidelines, have been shown to improve pain significantly vs placebo in low back pain but the magnitude of the effect was small, and NSAIDs have also not shown superiority over paracetamol in this indication.
“Because NSAIDs have a less favourable safety profile than has paracetamol and are not clearly better at pain reduction, they are not considered as the first option for analgesic prescription for patients with low-back pain,” the editorialists conclude.
The study was funded by the National Health and Medical Research Council of Australia and GlaxoSmithKline Australia. Two coauthors report receiving funding for a postgraduate research scholarship from GlaxoSmithKline, and funding to review teaching materials prepared by GlaxoSmithKline. The other authors, including Dr. Williams, have disclosed no relevant financial relationships.
Lancet. Published online July 24, 2014.