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

Clin Ther. 2003 Apr;25(4):1123-41. doi: 10.1016/s0149-2918(03)80071-1.


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 >/=40 mm 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 >/=1 dose of study medication and had >/=1 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 </= 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage*
  • Acetaminophen / adverse effects
  • Acetaminophen / therapeutic use
  • Adult
  • Aged
  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / therapeutic use
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Low Back Pain / drug therapy*
  • Male
  • Middle Aged
  • Pain Measurement
  • Tramadol / administration & dosage*
  • Tramadol / adverse effects
  • Tramadol / therapeutic use
  • Treatment Outcome


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Drug Combinations
  • Acetaminophen
  • Tramadol