Pain
A Systematic Review and Mixed Treatment Comparison of the Efficacy of Pharmacological Treatments for Fibromyalgia

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Objectives

To review the literature on pharmacological treatments for fibromyalgia.

Methods

Relative efficacy was estimated in terms of outcome measures highlighted by the Outcome Measures in Rheumatology Network using a Bayesian mixed treatment comparison (MTC) meta-analysis. Randomized controlled trials reporting treatments for fibromyalgia were identified by systematically reviewing electronic databases (Cochrane Library, Medline, EMBASE; accessed February 2008) and conducting manual bibliographic searches.

Results

Forty-five randomized controlled trials met the prespecified inclusion criteria for the systematic review. There were limited robust clinical data for some therapeutic classes (tricyclic antidepressants, analgesics, sedative hypnotics, monoamine oxidase inhibitors) and only 21 studies met the more stringent criteria for inclusion in the MTC. The majority of studies included in the MTC assessed the anticonvulsant pregabalin (n = 5) or the serotonin norepinephrine reuptake inhibitors (SNRIs) duloxetine (n = 3) and milnacipran (n = 3). Licensed doses of pregabalin and duloxetine were significantly (P < 0.05) more efficacious than placebo in terms of absolute reduction in pain, number of “responders” (≥30% reduction in pain), or change in Fibromyalgia Impact Questionnaire score (pregabalin 450 mg/d only). There was no significant difference between licensed doses of pregabalin and duloxetine for these outcomes. However licensed doses of pregabalin produced significantly greater improvements in sleep compared with milnacipran (as measured by Medical Outcomes Study Sleep Scale).

Conclusions

The current study confirms the therapeutic efficacy of pregabalin and the SNRIs, duloxetine and milnacipran, in the treatment of fibromyalgia. Given their different modes of action, combination therapy with pregabalin plus an SNRI should be investigated in future research.

Section snippets

Systematic Review

A systematic review of electronic databases and conference proceedings was conducted to identify relevant studies. Medline, Embase, and the Cochrane Library were accessed on 28 February 2008. The search combined the terms “fibromyalgia” and “fibrositis” and publication type “controlled clinical trial” or “randomized controlled trial.” The following conference proceedings were hand-searched (2003–2008 inclusive): World Congress of Pain, British Pain Society, World Institute of Pain, American

Systematic Review

In total, 464 studies were identified (following removal of duplicates), of which 378 were excluded on the basis of title and abstract (Fig. 1). A further 34 relevant publications were identified from searching reference lists and conference proceedings. Seventy-five publications were excluded on examination of the full article, leaving a total of 45 RCTs that were included in the systematic review. Study characteristics for the included publications are reported in the online appendix. Across

Discussion

The present analysis extends previous research by comparing different treatments using MTC. The result of our analyses found few statistically significant differences between FDA-approved treatments. The absolute difference between pregabalin and duloxetine was very small and did not reach statistical significance at licensed doses. Pregabalin produced significantly greater improvements in sleep (MOS sleep scores) compared with milnacipran at licensed doses. Although pregabalin, milnacipran,

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    This review was funded by Pfizer Ltd.

    Zahava Gabriel is a paid employee of Pfizer Ltd.

    Ernest Choy, David Marshall, Stephen Mitchell, Elizabeth Gylee, and Helen Dakin undertook paid consultancy work for Pfizer Ltd.

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