A randomized, double-blind, 8-week crossover study of once-daily controlled-release tramadol versus immediate-release tramadol taken as needed for chronic noncancer pain.

摘要

OBJECTIVE:: The purpose of this study was to evaluate the efficacy of controlled-release (CR) tramadol and immediate-release (IR) tramadol in patients with moderate or greater intensity chronic noncancer pain. METHODS:: A total of 122 patients underwent washout from all opioids 2 to 7 days before randomization to 1 of 2 groups: active CR tramadol 200 mg every morning plus placebo IR tramadol 50 mg every 4 to 6 hours PRN rescue, or placebo CR tramadol 200 mg every morning plus active IR tramadol 50 mg every 4 to 6 hours PRN rescue. After 2 weeks, the doses were increased to CR tramadol 400 mg or placebo and IR tramadol 100 mg every 4 to 6 hours PRN or placebo, as rescue. After 4 weeks in the first phase, patients crossed over to the alternative treatment for another 4 weeks. Pain intensity (100-mm visual analog scale [VAS] and 5-point ordinal scales) was assessed twice daily in diaries. Pain intensity, Pain and Disability Index (PDI; 0-10 ordinal scale), Pain and Sleep Questionnaire (100-mm VAS), and analgesic effectiveness (7-point ordinal scale) were assessed at biweekly clinic visits. RESULTS:: Sixty-five patients (35 men, 30 women) completed the study. Mean (SD) age was 56.5 (12.7) years; mean (SD) weight was 82.0 (18.5) kg. Daily diary pain intensity (mean [SD]) was significantly lower in the CR tramadol group than in the IR tramadol group in the last 2 weeks of each phase (completers: VAS, 29.9 [20.5] vs 36.2 [20.4] mm, P < 0.001; ordinal scale, 1.41 [0.7] vs 1.64 [0.6], P < 0.001; intent-to-treat [ITT] population: VAS, 32.5 [22.9] vs 38.6 [21.2] mm, P < 0.003; ordinal scale, 1.50 [0.8] vs 1.72 [0.7], P < 0.002). The overall pain intensity scores from the daily diary were also significantly better with CR tramadol for both the completers and ITT. Similar results were obtained on the biweekly VAS pain intensity questionnaire. No differences were found between treatments in total PDI or overall Pain and Sleep scores in either population. For the completers, both patients and investigators rated effectiveness higher for CR tramadol than for IR tramadol (P < 0.004 and P < 0.008 for patients and investigators, respectively). CONCLUSION:: This study reports significant improvement in pain intensity with CR tramadol as compared with IR tramadol.