Oral non-benzodiazepine muscle-relaxants for people with acute and chronic primary low back pain: a systematic review with meta-analysis

Purpose: To determine benefits and adverse effects (AE) of oral muscle-relaxants (MR) (non-benzodiazepines) for acute (< 6 weeks) and chronic (> 12 weeks) primary LBP, administered alone or combined with analgesics/NSAIDs. Methods: CENTRAL, MEDLINE, EMBASE, CINAHL were searched for pertinent randomized controlled trials. Primary outcomes comprised lack of pain relief, global efficacy and AE at 5–7 days follow-up assessed dichotomously (risk ratio, RR). Results: Fifty studies (7531 participants) were included, with data from 4775 pooled in meta-analyses. For acute LBP, non-benzodiazepine MR were associated with increased likelihood of pain relief (moderate certainty; RR: 0.53, p < 0.0001), global efficacy (RR: 0.49, p = 0.0001), muscle spasm (RR: 0.62, p < 0.00001), and physical outcomes (RR: 0.60, p < 0.00001) compared to placebo. AE were more frequent with non-benzodiazepine MR compared to placebo (low-to-moderate certainty; RR: 1.56; p = 0.003), and at central nervous system (CNS; RR: 2.40; p < 0.00001), but not at gastrointestinal (GI) level (RR: 0.77; p = 0.62). Combined non-benzodiazepines + analgesics/non-steroidal anti-inflammatory drugs (NSAIDs) provide a larger and clinically meaningful benefit compared to placebo + analgesics/NSAIDs for global efficacy at 5–7 days (low-certainty; RR: 0.62; p = 0.01). Combined therapy did not result in significant between-group differences for total AE (moderate-certainty; RR: 1.15; p = 0.50) and GI AE (RR: 0.63; p = 0.08), despite responsible for more CNS AE (low-certainty; RR: 1.91; p = 0.002). When comparing non-benzodiazepine MR versus placebo for chronic LBP, only data on total AE could be pooled, without between-group difference (RR: 0.93; p = 0.69). Conclusions: Non-benzodiazepine MR for acute LBP were associated with increased likelihood of pain relief and global efficacy compared to placebo. Combined therapy with analgesics/NSAIDs proved superior for global efficacy. Studies are needed to evaluate if non-benzodiazepine MR are of larger benefit than analgesics/NSAIDs, and if stand-alone administration provides more benefit than combined treatment. The observed AE warrant caution.