Higher-quality randomized controlled trials of head-to-head comparisons are needed, study investigator Michael A. Wewege, PhD candidate, research fellow, University of New South Wales and Neuroscience Research Australia, Sydney, said in an interview.
“Until then, doctors should use caution when prescribing analgesic medicines for adults with nonspecific acute low back pain. They should use this new evidence in line with their own expertise and the patient sitting in front of them when making any decision about a medication,” he added.
The findings were published online in the BMJ.
Poor quality evidence
Analgesics such as ibuprofen, acetaminophen, and codeine are widely used to treat nonspecific low-back pain, which is defined as pain lasting less than 6 weeks, but evidence for the comparative efficacy of these agents is limited.
To fill this knowledge gap, the researchers conducted a systematic review and analysis of controlled trials comparing analgesics with another analgesic, placebo, or no treatment in patients with acute, nonspecific low back pain.
The review involved 98 randomized controlled trials that included 15,134 adults (49% women) aged 30-60 years with pain duration ranging from 24 hours to 21 days. The median baseline pain intensity was 65 on a pain scale of 0-100.
Of the included trials, 39% were placebo controlled, 67% masked both participants and clinicians, and 41% reported industry sponsorship.
The studies compared an analgesic medicine with another analgesic, placebo, or no treatment comprised of usual care or being placed on a wait list.
Study medications, which had to be approved in the United States, Europe, or Australia, included nonsteroidal anti-inflammatory drugs, paracetamol, opioids, anticonvulsants, antidepressants, muscle relaxants, and corticosteroids.
These drugs were administered systemically as a single drug or in combination formulations, at any dose.
Researchers used a network meta-analysis, which combines direct and indirect information across a network of randomized clinical trials to estimate the comparative effectiveness of multiple treatments.
The primary outcomes were reductions in low back pain intensity (measured with a visual analogue scale), numerical rating scale or another ordinal scale, and safety as indicated by the number of participants who had any adverse event.
Investigators found several medications were associated with large reductions in pain intensity, compared with placebo, though with low or very low confidence.
Low or very low confidence was found for reduced pain intensity after treatment with tolperisone (mean difference, −26.1; 95% confidence interval, −34.0 to −18.2), aceclofenac plus tizanidine (mean difference, −26.1; 95% CI, −38.5 to −13.6), pregabalin (mean difference, −24.7; 95% CI, −34.6 to −14.7), and 14 other medicines, compared with placebo, the researchers report.
In addition, they found low or very low confidence for no difference between the effects of several of these medications.
Increased adverse events had moderate to very low confidence with tramadol (risk ratio, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), baclofen (RR, 2.3; 95% CI, 1.5-3.4), and paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), compared with placebo, the investigators add.
“These medicines could increase the risk of adverse events, compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes,” the researchers note.
The review suggested 14 additional comparisons favored the treatment over placebo, all with very low confidence except for one with low confidence.
In the 68 trials that included the number of participants reporting an adverse event, there was moderate confidence for increased adverse events with the opioid tramadol (RR, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), and low confidence for baclofen (RR, 2.3; 1.5-3.4), compared with placebo.
The review also uncovered moderate to low confidence for secondary outcomes, which included low back-specific function, serious adverse events, and acceptability (number of participants who dropped out).