Clinical study
Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study

https://doi.org/10.1016/S0002-9343(03)00116-5Get rights and content

Abstract

Purpose

To evaluate the efficacy and safety of a combination analgesic tablet (37.5 mg tramadol/325 mg acetaminophen) for the treatment of fibromyalgia pain.

Methods

This 91-day, multicenter, double-blind, randomized, placebo-controlled study compared tramadol/acetaminophen combination tablets with placebo. The primary outcome variable was cumulative time to discontinuation (Kaplan-Meier analysis). Secondary measures at the end of the study included pain, pain relief, total tender points, myalgia, health status, and Fibromyalgia Impact Questionnaire scores.

Results

Of the 315 subjects who were enrolled in the study, 313 (294 women [94%], mean [± SD] age, 50 ± 10 years) completed at least one postrandomization efficacy assessment (tramadol/acetaminophen: n = 156; placebo: n = 157). Discontinuation of treatment for any reason was less common in those treated with tramadol/acetaminophen compared with placebo (48% vs. 62%, P = 0.004). Tramadol/acetaminophen-treated subjects also had significantly less pain at the end of the study (53 ± 32 vs. 65 ± 29 on a visual analog scale of 0 to 100, P <0.001), and better pain relief (1.7 ± 1.4 vs. 0.8 ± 1.3 on a scale of –1 to 4, P <0.001) and Fibromyalgia Impact Questionnaire scores (P = 0.008). Indexes of physical functioning, role-physical, body pain, health transition, and physical component summary all improved significantly in the tramadol/acetaminophen-treated subjects. Discontinuation due to adverse events occurred in 19% (n = 29) of tramadol/acetaminophen-treated subjects and 12% (n = 18) of placebo-treated subjects (P = 0.09). The mean dose of tramadol/acetaminophen was 4.0 ± 1.8 tablets per day.

Conclusion

A tramadol/acetaminophen combination tablet was effective for the treatment of fibromyalgia pain without any serious adverse effects.

Section snippets

Study design and sample

This out-patient multicenter, randomized, double-blind, placebo-controlled study was conducted in adult subjects aged 18 to 75 years with at least moderate pain from fibromyalgia, defined as ≥40 mm on a 100-mm pain visual analog scale. All subjects fulfilled the 1990 American College of Rheumatology classification guidelines for the diagnosis of fibromyalgia (2). Subjects were also required to be in general good health, and women were required to be practicing contraception or incapable of

Results

A total of 315 subjects were assigned randomly to tramadol/acetaminophen (n = 158) or placebo (n = 157), of whom 313 were evaluable for efficacy and 312 were evaluable for safety (Figure 2). Subjects ranged in age from 19 to 75 years; most were women and white (Table 1). The mean (± SD) pain score at baseline (on a 0- to 100-mm visual analog scale) was 72 ± 15 mm (Table 2). There were no significant baseline differences between the two groups (Table 1, Table 2, Table 3).

Primary efficacy outcome

The cumulative rate of discontinuation of therapy for any reason was significantly lower in the tramadol/acetaminophen group (48% by day 91) than in the placebo group (62% by day 91; P = 0.004; Figure 3A). The cumulative rate of discontinuation due to lack of efficacy was also significantly lower in the tramadol/acetaminophen group (29% by day 91) than in the placebo group (51% by day 91; P <0.001; Figure 3B).

Secondary outcome measures

Compared with placebo, the mean final pain score was about 12 mm (18%) lower in the tramadol/acetaminophen group (Table 2; P <0.001). Similarly, mean final pain relief was significantly better in the tramadol/acetaminophen group than in the placebo group (Table 2; P <0.001). Subjects in the tramadol/acetaminophen group also had a significantly greater decrease in the number of tender points during the trial, and lower average myalgic scores at the end of the trial (Table 2).

Forty-two percent

Safety

A total of 156 subjects in each group were evaluated for safety. Subjects in the tramadol/acetaminophen group took an average of 151 mg/d of tramadol and 1238 mg/d of acetaminophen (mean daily dose of 4.0 ± 1.8 tablets). Adverse events, regardless of relation to study medication, led to study discontinuation in 19% (n = 29) of tramadol/acetaminophen subjects and 12% (n = 18) of placebo subjects (P = 0.09; Figure 2). In all, 118 subjects (76%) in the tramadol/acetaminophen group reported at

Discussion

The results of this study demonstrate that a 37.5-mg tramadol/325-mg acetaminophen combination tablet is a safe, moderately effective, and well-tolerated medication for the treatment of fibromyalgia pain and related symptoms. Although subjects in the tramadol/acetaminophen group had a statistically significant improvement in the primary outcome measure and many of the secondary outcome measures as compared with placebo-treated subjects, improvements from baseline values in the placebo group

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    This study was supported by a grant (CAPSS-113) from Ortho-McNeil Pharmaceutical, Inc, Raritan, New Jersey. All investigators were financially reimbursed by Ortho-McNeil Pharmaceutical for conducting this study.

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