Tramadol for the treatment of joint pain associated with osteoarthritis: A randomized, double-blind, placebo-controlled trial

Background: Results from short-term, non-placebo-controlled clinical trials suggest that tramadol is effective as adjunctive therapy for the treatment of joint pain associated with osteoarthritis COA). Objective: We assessed the efficacy and tolerability of tramadol monotherapy versus placebo in the treatment of joint pain associated with OA. Methods: Patients with symptomatic OA of the knee and at least moderate pain at the end of a 10-day analgesic washout period were randomized to receive tramadol or placebo. After a 7-day titration period (50-mg increments every 2 days to a target dosage of 200 mg/d), patients were permitted to increase their dose up to 400 mg/d as needed for 84 days. Likert scale scores to assess pain intensity (none = 0 to extreme = 4) and pain relief (complete relief = 3 to severely worse = -3) as well as Western Ontario and McMaster Universities (WOMAC) OA Index scores were obtained at visits on days 14, 28, 56, and 91 of the study. Patient and investigator global assessments of treatment effectiveness were recorded at the final visit (day 91 or at the time of discontinuation). Results: Baseline characteristics were similar for the tramadol (n = 63) and placebo (n = 66) groups; move than half of the patients (mean age 62.5 years) were women (65.1% and 59.1% in the tramadol and placebo groups, respectively). Mean final pain intensity scores were 2.10 in the tramadol group and 2.48 in the placebo group (P = 0.082, analysis of covariance). Tramadol was significantly more effective than placebo for all secondary outcomes: mean final pain intensity scores (P = 0.045, t test), pain relief scores (P = 0.004), patient and investigator global assessments (P = 0.038 and P = 0.001, respectively), median time to failure of effectiveness (P = 0.042), and all WOMAC scores (P less than or equal to 0.033). Fourteen tramadol, and 10 placebo patients discontinued the study because of adverse events (AEs). Other reasons for discontinuation included lack of efficacy (26 tramadol and 43 placebo patients) and patient choice (10 tramadol and 11 placebo patients). The most common AEs during tramadol therapy were nausea, constipation, dizziness, Pruritus, and headache; no serious AEs, seizures, or cases of abuse were reported in the tramadol group. Conclusion: Tramadol may be useful as monotherapy in the treatment of joint pain associated with OA.