Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain - A randomized, double-blind, placebo-controlled study

Objective. To demonstrate that in patients receiving naproxen for the pain of osteoarthritis (OA), the addition of tramadol will allow a reduction in the naproxen dosage without compromising pain relief. Methods. This trial consisted of a 5-week open-label run-in and an 8-week d ouble-blind phase. Patients with at least moderate pain (greater than or eq ual to 40 mm on a 100-mm visual analog scale) of OA of the knee after a 1-w eek medication washout were treated with naproxen 500 mg/day for 1 week. Pa tients whose pain scores were reduced to <20 mm were discontinued. The rema ining patients received naproxen 1,000 mg/day for 3 weeks. Tramadol 200 mg/ day was added during the third week Patients were then randomized in a doub le-blind manner to continue tramadol 200 mg/day or to begin placebo in addi tion to naproxen, Randomization was stratified based on response to naproxe n 1,000 mg/day, During the double-blind phase, the naproxen dose was reduce d by 250 mg every 2 weeks. The primary efficacy end point was the minimum e ffective naproxen dose (MEND), The MEND was defined as 250 mg above the nap roxen daily dosage at which pain relief was no longer adequate. Patients di scontinuing the double-blind phase of the study for reasons other than lack of efficacy were assigned a MEND equal to the last naproxen dose received, If the effect of treatment between the responder and nonresponder groups w as statistically different, the difference in the MEND was assessed separat ely within the groups. Results. Of 236 patients randomized (mean age 61 Sears; 147 females), 90 we re stratified as naproxen responders and 146 as naproxen nonresponders. The re was a significant difference (P = 0.040) in the treatment effect between the naproxen responders and nonresponders, thus demonstrating a difference in the way responders and nonresponders react to a decrease in naproxen do sage after the addition of tramadol. Among naproxen responders, the MEND wa s significantly lower in patients receiving tramadol (n = 36) than in patie nts receiving placebo (n = 54), 221 mg versus 407 mg, respectively (P = 0.0 21). For the naproxen nonresponders, the mean MEND was 419 mg in the tramad ol group and 396 mg in the placebo group (P = 0.706). Conclusion, In patients with painful OA of the knee responding to naproxen 1,000 mg/day, the addition of tramadol 200 mg/day allows a significant redu ction in the dosage of naproxen without compromising pain relief.