238 A Randomized Clinical Trial of Naproxen + Placebo, Orphenadrine, or Methocarbamol for Acute Low Back Pain

Abstract

Low back pain (LBP) causes more than 2.5 million visits to US EDs annually. LBP patients are often treated with non-steroidal anti-inflammatory drugs (NSAIDs) and skeletal muscle relaxants (SMRs). We compared functional outcomes and pain one week and three months after ED discharge among patients randomized to a one-week course of naproxen+ placebo vs naproxen+orphenadrine vs. naproxen+ methocarbamol. Orphenadrine and methocarbamol are each used in more than 250,000 ED visits annually. This was a randomized, double-blind, comparative efficacy trial conducted in two urban EDs. Patients presenting with acute, non-traumatic, non-radicular LBP of ≤ 2 weeks duration were eligible for enrollment immediately prior to discharge from an ED if they had a score >5 on the Roland-Morris Disability Questionnaire (RMDQ), a validated 24-item inventory of functional impairment due to LBP. Higher scores on the RMDQ indicate greater functional disability. The primary outcome was improvement on the RMDQ between ED discharge and one week later. Secondary outcomes included pain intensity one week and three months after ED discharge, as measured on a four-point descriptive scale (severe, moderate, mild, none). All patients were given 14 tablets of naproxen 500mg, to be taken twice a day, as needed for LBP. Additionally, patients were randomized to receive a one-week supply of orphenadrine 100mg, to be taken twice a day as needed for LBP, methocarbamol 750mg, to be taken as one or two tablets, three times per day, as needed for LBP, or placebo. All patients received a standardized 10-minute LBP educational session prior to discharge. Using a between-group mean difference of 5 RMDQ points, a previously validated threshold for clinical significance, a 2-tailed α=0.05 and β=0.2, we calculated a required sample size of 240 patients. Enrollment commenced in March 2016 and continued for 11 months. 1,473 patients were screened for eligibility. 240 patients met entry criteria and were randomized. Baseline demographic characteristics were comparable between the two groups. 234 patients (98%) provided one-week outcome data. The mean RMDQ of patients randomized to naproxen + placebo improved by 10.9 (95% CI: 8.9, 12.9) RMDQ points. The mean RMDQ of patients randomized to naproxen + orphenadrine improved by 9.4 (95% CI: 7.4, 11.5). The mean RMDQ of patients randomized to naproxen + methocarbamol improved by 8.1 (95% CI: 6.1, 10.1). None of the between-group differences achieved the threshold for clinical significance. At one-week follow-up, 34% (95% CI: 25, 45%) of naproxen+placebo patients reported moderate or severe LBP versus 33% (95% CI: 24, 44%) of naproxen+orphenadrine patients and 39% (95% CI: 29, 50%) of naproxen+methocarbamol patients. At three-month follow-up, 19% (95% CI: 11, 30%) of naproxen+placebo patients reported moderate or severe LBP versus 17% (95% CI: 10, 28%) of naproxen+orphenadrine patients and 21% (95% CI: 13, 33%) of naproxen+methocarbamol patients. Adverse events were reported by 17% (95% CI: 10, 28%) of naproxen+placebo patients, 9% (95% CI: 4, 19%) of naproxen+orphenadrine patients, and 19% (95% CI: 11, 29%) of naproxen+methocarbamol patients. Among ED patients with acute, non-traumatic, non-radicular LBP, combining naproxen with either orphenadrine or methocarbamol did not improve functional outcomes or pain one week and three months after ED discharge when compared to naproxen + placebo.