Comparative Efficacy, Safety of Analgesics to Treat Acute Low Back Pain Questioned

The comparative safety and efficacy of analgesics commonly used to treat acute low back pain (LBP) are unclear, concluded Australian researchers writing in a recent issue of The BMJ. The investigators urge caution in prescribing and using the medications until findings from higher quality head-to-head randomized controlled trials (RCT) are available.

The guidance is based on a comprehensive systematic literature review and network meta-analysis comprised of 98 RCT with low or very low confidence noted in the evidence for reduced intensity of pain and increased adverse events.

Guideline-recommended care of non-specific acute LBP (lasting for <6 weeks) suggests physical activity and self-management as first line therapy and nonpharmacologic interventions (eg, physical therapy) and analgesics as second-line. Although there are studies evaluating the efficacy of a range of analgesic medications compared with placebo, there is very limited evidence for comparative effectiveness, the authors state.

“Clinicians who prescribe medicines for low back pain must choose between medicines with different analgesic properties and safety profiles,” wrote Michael A Wewege, doctoral candidate at the School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, and colleagues. Thus far, “no comprehensive evaluation of individual medicines is available to inform clinical decision making for the best medicine for acute non-specific low back pain.”

To help fill the gaps in evidence, Wewege and team launched a systematic literature review and meta-analysis, beginning with a search of databases including Medline, PubMed, Embase, and Clinicaltrials.gov from inception through February 2022 for RCT comparing analgesic medicines with another analgesics, placebo, or no treatment in patients reporting acute non-specific low back pain. Analgesics were defined as nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, corticosteroids, antidepressants, paracetamol, anti-convulsants, and skeletal muscle relaxants. Eligible RCTs involved adults who reported acute non-specific low back pain for a period of less than 6 weeks.

The primary outcomes of interest were low back pain intensity at the end of treatment (on a 0-100-point scale) and safety (number of participants who reported any adverse event during treatment). Researchers identified secondary outcomes as serious adverse events, low back specific function, and treatment discontinuation.

Wewege et al identified 124 relevant trials of which 98 RCTs, published between 1964 and 2021, were included in their final analysis. Final participant count was 15 134; 51% were men and mean age across RCT ranged from 30 to 60 years. Pain duration ranged from 24 hours to 21 days and median pain intensity at baseline for all trials was 65/100. Studies included 169 different analgesics or combinations (42 as monotherapy, 27 as combinations).

Duration of treatment ranged from 1 day to 42 days.

Investigators used a validated risk tool to evaluate risk of bias for each study.

FINDINGS

The researchers noted low or very low confidence in evidence for reduced pain intensity after treatment with muscle relaxant tolperisone, (mean difference −26.1; 95% CI −34.0 to −18.2), pregabalin (−24.7; 95% CI −34.6 to −14.7), aceclofenac plus tizanidine (−26.1; 95% CI −38.5 to −13.6), in addition to 14 other medicines, when compared with placebo. Wewege and colleagues also noted very low confidence for no difference between the effects of several of these medications.

Large reductions in pain. For statistically significant reductions, the research team noted very low confidence reported for large reductions in pain intensity (mean difference >20 points) for 4 medicines (eg, thiocolchicoside, ketoprofen), moderate reductions (10-20 points) for 7 medicines (eg, aceclofenac, etoricoxib, ketorolac) and small reductions (5-10 points) for 3 medicines including ibuprofen and paracetamol. 

Adverse event outcomes. The researchers noted moderate to very low confidence evidence for increased adverse events, such as nausea, vomiting, drowsiness, dizziness, and headache, with tramadol (risk ratio [RR] 2.6; 95% CI 1.5 to 4.5]), baclofen (2.3; 95% CI 1.5 to 3.4), paracetamol plus tramadol (2.1; 95% CI 1.3 to 3.4), and paracetamol plus sustained release tramadol (2.4; 95% CI 1.5 to 3.8) compared to placebo. Moderate to low confidence evidence also suggested that these medications could increase the risk of adverse events compared to other medications.

The study also found similar moderate to low confidence evidence for other secondary outcomes, including serious adverse events and discontinuation from treatment, as well as a secondary analysis of medication classes.

Wewege and team note that while their review was comprehensive and the literature search extensive, most of the final studies included in their analysis expressed concern related to risk of bias. This fact along with several other limitations may have had some impact on their results, they said.

"Our review of analgesic medicines for acute non-specific low back pain found considerable uncertainty around effects for pain intensity and safety,” they write. As such, they say clinicians and patients “are advised to take a cautious approach to the use of analgesic medicines.”

Reference: Wewege MA, Bagg MK, Jones MD, et al. Comparative effectiveness, and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis. BMJ. 20232023;380:e072962. Published online March 22, 2023. doi:10.1136/bmj-2022-072962