Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: A multicenter, randomized, double-blind, placebo-controlled outpatient study

Background: Tramadol and acetaminophen (APAP) have both shown efficacy in the treatment of lower back pain. The combination of these 2 agents has demonstrated synergistic analgesic action in animal models at specific ratios. Objective: This study assessed the long-term (3-month) efficacy and safety of tramadol 37.5 mg/APAP 325 mg combination tablets in the treatment of chronic lower back pain. Methods: Patients with at least moderate lower back pain (pain visual analog [PVA] score greater than or equal to40 min on a 100-mm scale) were randomized to receive up to 8 tablets of tramadol/APAP per day or placebo for 91 days. Medication was titrated from 1 to 4 tablets/d by day 10. The primary efficacy measure was PVA score at the final visit. Secondary measures included scores on the Pain Relief Rating Scale (PRRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Roland Disability Questionnaire (RDQ), and 36-Item Short-Form Health Survey (SF-36); the incidence of discontinuation due to insufficient pain relief (Kaplan-Meier analysis); and overall assessments of medication by the patients and investigators. Results: Three hundred eighteen patients (161 tramadol/APAP, 157 placebo) were included in the intent-to-treat population, defined as all patients who took greater than or equal to1 dose of study medication and had greater than or equal to1 postrandomization. efficacy measurement. The mean age of the study population was 53.9 years, 63.2% were female, 90.3% were white, and the mean baseline PVA score was 70.0 mm. There were no significant differences between groups at baseline. Tramadol/APAP significantly improved final PVA scores (P = 0.015) and final PRRS scores (P < 0.001) compared with placebo. Tramadol/APAP also significantly improved RDQ scores (P less than or equal to 0.027) and scores on many subcategories of the SF-MPQ, including total score (P = 0.021). The tramadol/APAP group had significant improvements on the role-physical (P = 0.005), bodily pain (P = 0.046), role-emotional (P = 0.001), mental health (P = 0.026), reported health transition (P = 0.038), and mental component summary (P = 0.008) subscales of the SF-36. The cumulative incidence of discontinuation due to insufficient pain relief was 22.1% for tramadol/APAP and 41.0% for placebo (P < 0.001). Treatment-emergent adverse events in the tramadol/APAP group included nausea (13.0%), somnolence (12.4%), and constipation (11.2%). Conclusions: In this study, tramadol 37.5 mg/APAP 325 mg combination tablets were effective and had a favorable safety profile in the treatment of chronic lower back pain. Copyright (C) 2003 Excerpta Medica, Inc.