Clinical studyTramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study☆
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
References (40)
Emerging concepts in the neurobiology of chronic painevidence of abnormal sensory processing in fibromyalgia
Mayo Clin Proc
(1999)The rational management of fibromyalgia patients
Rheum Dis Clin North Am
(2002)- et al.
A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia
Am J Med
(2002) - et al.
A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia
Am J Med
(1998) The neuropharmacology of centrally-acting analgesic medications in fibromyalgia
Rheum Dis Clin North Am
(2002)- et al.
Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare paina multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study
Clin Ther
(2002) - et al.
High-dose tramadol in comparison to low-dose morphine for cancer pain relief
J Pain Symptom Manage
(1999) - et al.
Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy
J Diabetes Complications
(2000) - et al.
The effect of a paracetamol and morphine combination on dynorphin A levels in the rat brain
Biochem Pharmacol
(2001) - et al.
The effect of paracetamol on nociception and dynorphin A levels in the rat brain
Neuropeptides
(2001)
A postmarketing surveillance program to monitor Ultram® (tramadol hydrochloride) abuse in the United States
Drug Alcohol Depend
Fibromyalgiawhere are we a decade after the American College of Rheumatology classification criteria were developed?
Arthritis Rheum
The American College of Rheumatology 1990 criteria for the classification of fibromyalgiareport of the Multicenter Criteria Committee
Arthritis Rheum
Evidence of involvement of central neural mechanisms in generating fibromyalgia pain
Curr Rheumatol Rep
Central hyperexcitability in chronic musculoskeletal paina conceptual breakthrough with multiple clinical implications
Pain Res Manag
Psychiatric diagnoses in patients with fibromyalgia are related to health care-seeking behavior rather than to illness
Arthritis Rheum
Short term effects of ibuprofen in primary fibromyalgia syndromea double blind, placebo controlled trial
J Rheumatol
Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolama double-blind, placebo-controlled study
Arthritis Rheum
A comparison of cyclobenzaprine and placebo in the management of fibrositisa double-blind controlled study
Arthritis Rheum
A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia
Arthritis Rheum
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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.