The Role of Antidepressants in the Management of Fibromyalgia Syndrome
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.
- 16.Burckhardt CS, Goldenberg D, Crofford L, et al. Guideline for the management of fibromyalgia syndrome: pain in adults and children. APS Clinical Practice Guideline Series No. 4. Glenview (IL): American Pain Society, 2005Google Scholar
- 20.Briley M. Drugs to treat fibromyalgia: the transatlantic difference. Curr Opin Inves Drugs 2010; 11: 16–8Google Scholar
- 29.Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale (NJ): Lawrence Erlbaum Associates, 1988Google Scholar
- 30.Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions, version 5.1.0, updated March 2011 [online]. Available from URL: http://www.cochrane-handbook.org/ [Accessed 2011 Dec 6]
- 32.Kelly J. Pfizer stops work on esreboxetine for FM [online]. Available from URL: http://www.mskreport.com/articles.cfm?articleID=3293 [Accessed 2011 Feb 23]
- 33.Häuser W, Bartram C, Bartram-Wunn E, et al. Systematic review: adverse events attributable to nocebo in randomised controlled drug trials in fibromyalgia syndrome and painful diabetic peripheral neuropathy. Clin J Pain. Epub 2012 Feb 14Google Scholar
- 35.Drugs information online. Duloxetine [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf [Accessed 2011 Aug 15]
- 36.Drugs information online. Milnacipran [online]. Available from URL: http://www.drugs.com/pro/savella.html [Accessed 2011 Aug 15]
- 37.Drugs information online. Fluoxetine [online]. Available from URL: http://www.drugs.com/pro/fluoxetine.html [Accessed 2011 Aug 15]
- 38.Drugs information online. Paroxetine [online]. Available from URL: http://www.drugs.com/pro/paxil.html [Accessed 2011 Aug 15]
- 39.Drugs information online. Amitriptyline [online]. Available from URL: http://www.drugs.com/pro/amitriptyline.html [Accessed 2011 Aug 15]