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The Role of Antidepressants in the Management of Fibromyalgia Syndrome

A Systematic Review and Meta-Analysis

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Abstract

Background: The role of antidepressants in the management of fibromyalgia syndrome (FMS) still needs to be determined.

Objective: The objective of this study was to provide a quantitative analysis (meta-analysis) of the efficacy and harms of antidepressants in the management of adult FMS patients.

Data sources: The data sources used were the databases MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (until December 30, 2010), the reference lists of included articles, and the websites of the US National Institutes of Health (NIH) and the Pharmaceutical Research and Manufacturers of America (PhRMA).

Study selection: Studies with a randomized controlled trial (RCT) design comparing any types of antidepressants with pharmacological placebo or head-to-head comparisons of different types of antidepressants in FMS patients were included. RCTs in which antidepressants were combined with any other defined treatment or antidepressants were tested against anything but drug placebo were excluded. Patients diagnosed with FMS according to predefined criteria of any age were included. To be included, studies had to assess at least one key domain of FMS (pain, sleep, fatigue, health-related quality of life [HRQOL]) as outcomes of efficacy and report total treatment discontinuation rates and/or dropout rates due to adverse events as outcomes for harms.

Data extraction: Data were extracted according to protocols of previous systematic reviews on antidepressants in FMS. Methodology quality was assessed by the van Tulder score.

Data synthesis: Standardized mean differences (SMD) were calculated for continuous outcomes by means and standard deviations and relative risks (RR) for 30% pain reduction and total dropout rate for comparisons of antidepressants with placebo. Examination of the combined results was performed by a random effects model. We used Cohen’s categories to evaluate the magnitude of the effect size, calculated by SMD. Heterogeneity was tested by the I2 statistic.

Thirty-five studies were included in the meta-analysis. The SMDs of serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) on pain, sleep, fatigue, depression and HRQOL were significant. Based on Cohen’s categories, the effect size on pain was small and the ones on sleep, fatigue, depression and HRQOL were not substantial. 1481/3528 (42.0%) patients with SNRIs and 737/2304 (32.0%) patients with placebo reported a 30% pain reduction (number needed to treat [NNT] 10.0; 95% CI 8.00,13.4; I2=4%). The RR of dropouts due to adverse events was 1.83 (95% CI 1.53, 2.18; I2 = 33%).

The SMDs of selective serotonin reuptake inhibitors (SSRIs) on pain, sleep, depression and HRQOL were significant. Based on Cohen’s categories, the effect sizes on pain, depression and HRQOL were small and the one on sleep not substantial. 72/198 (36.4%) patients with SSRIs and 40/194 (20.6%) patients with placebo reported a 30% pain reduction (NNT 6.3; 95% CI 4.1,14.1). The RR of dropouts due to adverse events was 1.60 (95% CI 0.84, 3.04; I2=0%).

The SMDs of tricyclic antidepressants (TCAs) on pain, sleep, fatigue and HRQOL were significant. Based on Cohen’s categories, the effect sizes on pain and sleep were moderate and the ones on fatigue and HRQOL were small. 140/290 (48.3%) patients with TCAs and 70/252 (27.8%) patients with placebo reported a 30% pain reduction (NNT 4.9; 95% CI 3.5, 8.0). The RR of dropouts due to adverse events was 0.84 (95% CI 0.46, 1.52; I2 = 0%).

Conclusions: The TCA amitriptyline and the SNRIs duloxetine and milnacipran are first-line options for the treatment of FMS patients. Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.

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Acknowledgements

Dr Häuser received honoraria for one educational lecture from Janssen-Cilag. The National Data Bank for Rheumatic Diseases, the employer of Dr Frederick Wolfe, received a grant from Pfizer for conducting a fibromyalgia criteria study. Dr Tölle received grants within the innovative medicines initiative supported by Pfizer and payments for lectures including services on speakers’ bureaus from Pfizer, Eli-Lilly, Grünenthal and Astellas. Dr Üçeyler has no conflicts of interest to declare. Dr Sommer received honoraria for educational lectures from Pfizer and Eli-Lilly and has participated in advisory boards of these companies.

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Authors and Affiliations

  1. Department of Internal Medicine I, Clinical Center Saarbrücken, D-66119, Saarbrücken, Germany

    Winfried Häuser MD

  2. National Data Bank for Rheumatic Diseases, Wichita, KS, USA

    Frederick Wolfe

  3. University of Kansas School of Medicine, Wichita, KS, USA

    Frederick Wolfe

  4. Department of Neurology, University of Würzburg, Würzburg, Germany

    Thomas Tölle

  5. Department of Neurology, Technische Universität München, München, Germany

    Nurcan Üçeyler & Claudia Sommer

  6. Department of Psychosomatic Medicine, Technische Universität München, München, Germany

    Winfried Häuser MD

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Correspondence to Winfried Häuser MD.

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Häuser, W., Wolfe, F., Tölle, T. et al. The Role of Antidepressants in the Management of Fibromyalgia Syndrome. CNS Drugs 26, 297–307 (2012). https://doi.org/10.2165/11598970-000000000-00000

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