Uncertainty Surrounding Comparative Efficacy, Safety of Analgesic Medicines for Low Back Pain

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The comparative safety and effectiveness of analgesic medications for acute non-specific low back pain are unclear, highlighting the need for higher quality randomized controlled trials comparing different medications.

The comparative safety and effectiveness of analgesic medications for acute non-specific low back pain were unclear, according to a study published in The BMJ.1 Investigators encouraged patients and clinicians to take a cautious approach to manage low back pain with analgesic medications until higher quality randomized controlled trials (RCTs) comparing different medications are conducted.

Although physical activity and self-management of acute low back pain are generally recommended as first line care, second line care commonly involves non-pharmacological interventions, such as manual therapy, and analgesic medications.2

“Clinicians who prescribe medicines for low back pain must choose between medicines with different analgesic properties and safety profiles,” stated Michael A Wewege, doctoral candidate at the School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, and a team of investigators. 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.”

In this systematic review and network meta-analysis, the databases Medline, Embase, CENTRAL, PubMed,, CINAHL, and the World Health Organization’s International Clinical Trials Registry Platform were searched from inception through February 2022 to identify RCTs evaluating analgesic medicines compared with other analgesics, placebo, or no treatment. Analgesics were defined as nonsteroidal anti-inflammatory drugs, opioids, corticosteroids, antidepressants, paracetamol, anti-convulsant drug, 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 were low back pain intensity, on a scale of 0 – 100, at the end of treatment and safety, which was evaluated via the number of participants who reported adverse events during the treatment period. Secondary outcomes included serious adverse events, low back specific function, and treatment discontinuation. Two independent reviewers evaluated the risk of bias using the Cochrane tool for assessing risk of bias in randomized trials (RoB 2).

In total, 98 RCTs comprised of 15,134 participants, included 69 different medicines or combinations. Approximately half (51%) of participants were male. The mean age ranged predominantly between 30 and 60 years, with a pain duration ranging from 24 hours to 21 days, and a median pain intensity at baseline of 65/100.

Pain intensity was included in all RCTs. A low or very low confidence was reported regarding evidence for reduced pain intensity after treatment with tolperisone (mean difference −26.1 [95% confidence intervals (CIs) −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. Further, a low or very low confidence was reported for no difference between the effects of several of these medications.

An increased incidence of adverse events had moderate to very low confidence with tramadol (risk ratio 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]) when compared with placebo. These medicines may increase the risk of adverse events when compared with other medications with moderate to low confidence. Common adverse events included nausea, dizziness, vomiting, headache, and drowsiness.

A moderate to low confidence was reported regarding the secondary outcomes and secondary analysis of medicine class.

“Despite nearly 60 years of research involving more than 15 000 patients, high quality evidence to guide clinical decisions on analgesic medicines for acute non-specific low back pain remains limited,” investigators concluded.


  1. 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. 2023;380:e072962. Published 2023 Mar 22. doi:10.1136/bmj-2022-072962
  2. Almeida M, Saragiotto B, Richards B, Maher CG. Primary care management of non-specific low back pain: key messages from recent clinical guidelines. Med J Aust2018;208:272-5. doi:10.5694/mja17.01152 pmid:29614943