Results for each of the key questions are summarized in Table 10. Most skeletal muscle relaxants are FDA-approved for either spasticity (baclofen, dantrolene, and tizanidine) or musculoskeletal conditions (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) and were primarily evaluated for use in patients with the approved indication. The only drug with at least fair quality evidence of effectiveness for both types of conditions is tizanidine. Most head-to-head trials included in this report were performed in patients with multiple sclerosis or patients with acute neck or low back pain; almost all of the evidence regarding efficacy and safety in patients with other conditions comes from placebo-controlled trials.

Table 10. Summary of evidence.

Table 10

Summary of evidence.

In general, there was insufficient evidence to prove that different skeletal muscle relaxants are associated with different efficacy or safety. The best available evidence suggests that tizanidine is roughly equivalent to baclofen for most clinical outcomes in patients with spasticity. The comparative efficacy for other skeletal muscle relaxants and other conditions has not been established. In patients with musculoskeletal conditions, the largest body of head-to-head data is for cyclobenzaprine versus diazepam in patients with musculoskeletal conditions, but this data was inconclusive regarding differences in comparative efficacy. The data on adverse events is insufficient to distinguish any skeletal muscle relaxant with regard to overall safety, though the adverse event profile may differ between medications. There appears to be a small but significant risk of dantrolene-associated serious (including fatal) hepatic injury. Tizanidine appears to be associated with asymptomatic, reversible elevations of aminotransferases, and both tizanidine and chlorzoxazone have been associated with rare cases of serious hepatotoxicity. The available literature provides no data regarding the comparative risk of abuse and addiction from skeletal muscle relaxants, though there are numerous case reports, almost all of which are associated with carisoprodol.

A recent fair-quality randomized trial found that cyclobenzaprine 5 mg po tid provided equivalent effectiveness to 10 mg po tid doses, while being associated with fewer adverse events.47 Another fair-quality randomized trial found that cyclobenzaprine 5 mg po tid but not 2.5 mg po tid was more effective than placebo, and associated with fewer withdrawals (due to ineffectiveness) than the 2.5 mg po tid dose.47 A previous trial found that cyclobenzaprine 20 mg tid was not more effective than 10 mg po tid, and associated with more adverse events.25 This information could guide target doses in future trials, and similar information would be very useful for other skeletal muscle relaxants.