Fibromyalgia: Sommer C

Eich W, Häuser W, Friedel E, Klement A, Herrmann M, Petzke F, Offenbächer M, Schiltenwolf M, Sommer C, Tölle T, Henningsen P. · Abteilung Innere Medizin II, Universitatsklinikum Heidelberg, Heidelberg. · Z Rheumatol. · Pubmed #19050952 No free full text.

Abstract: BACKGROUND: Interdisciplinary guidelines for the definition, classification and diagnosis of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS) were developed by collaboration of 10 German medical and psychological associations and 2 patient self-help organizations. METHODS: A systematic literature search was performed in the Cochrane Library (1993-12/2006). Medline (1980-2006), and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Center for Evidence-Based Medicine. Grading of the strength of recommendation was done according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. RESULTS: CWP is defined by the criteria of the American College of Rheumatology (ACR-strong consensus). FMS can be diagnosed for clinical purposes by symptom-based criteria (without tender point examination) as well as by the ACR criteria (strong consensus).

Eich W, Häuser W, Friedel E, Klement A, Herrmann M, Petzke F, Offenbächer M, Schiltenwolf M, Sommer C, Tölle T, Henningsen P. · Abteilung Innere Medizin II (Allgemeine Klinische und Psychosomatische Medizin), Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69210, Heidelberg. · Schmerz. · Pubmed #18478271 No free full text.

Abstract: BACKGROUND: Interdisciplinary guidelines for the definition, classification and diagnosis of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS) were developed by collaboration of 10 German medical and psychological associations and 2 patient self-help organizations. METHODS: A systematic literature search was performed in the Cochrane Library (1993-12/2006), Medline (1980-2006), PsychInfo (1966-12/2006), and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strength of recommendation was done according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. RESULTS: CWP is defined by the criteria of the American College of Rheumatology (ACR--strong consensus). FMS can be diagnosed for clinical purposes by symptom-based criteria (without tender point examination) as well as by the ACR criteria (strong consensus).

Sommer C, Häuser W, Gerhold K, Joraschky P, Petzke F, Tölle T, Uçeyler N, Winkelmann A, Thieme K. · Neurologische Klinik, Universität Würzburg, Würzburg. · Schmerz. · Pubmed #18470541 No free full text.

Abstract: OBJECTIVE: To write a systematic review on the etiology and pathophysiology of the fibromyalgia syndrome (FMS) and of chronic widespread pain (CWP). METHODS: An interdisciplinary level-3 guideline (i.e. systematic literature search and assessment, logic analysis, formal consensus procedure) for the diagnosis and therapy of FMS was created in cooperation with 10 medical and psychological societies and 2 patient self-help organizations. A literature search was performed covering all available review articles on the etiology and pathophysiology of FMS and CWP using the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-2006), PsychInfo (1966-12/2006), and Scopus (1980-12/2006). For the assignment of evidence classes the system of the Oxford Centre for Evidence-Based Medicine was applied. Consensus was achieved by a multi-step nominal group procedure. RESULTS: FMS aggregates in families (evidence level 2c). Physical and psychological stress at the workplace are risk factors for the development of CWP and FMS. Affective disorders are risk factors for the development and maintenance of FMS. Operant learning mechanisms and sensitization are risk factors for the chronification of FMS (evidence levels 2b). Several factors are associated with the pathophysiology of FMS, but the causal relationship is unclear. This includes alterations of central pain pathways, hyporeactivity of the hypothalamus-pituitary-adrenal axis, increased systemic pro-inflammatory and reduced anti-inflammatory cytokine profiles and disturbances in the dopaminergic and serotonergic systems. CONCLUSIONS: FMS is the common final product of various etiological factors and pathophysiological mechanisms.

Sommer C, Häuser W, Berliner M, Brückle W, Ehlers S, Mönkemöller K, Moradi B, Petzke F, Uçeyler N, Wörz R, Winter E, Nutzinger DO. · Neurologische Klinik, Universität Würzburg, Würzburg. · Schmerz. · Pubmed #18458958 No free full text.

Abstract: BACKGROUND: An interdisciplinary guideline for the treatment of fibromyalgia syndrome (FMS) and chronic widespread pain (CWP) was developed in cooperation with ten German medical and psychological associations and two patients' self-help organizations. METHODS: Using the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-2006), PsychInfo (1966-12/2006), and Scopus (1980-12/ 2006) a systematic literature search was performed, which included all randomised controlled trials (RCT) evaluating multicomponent therapy in FMS and CWP. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. The strength of recommendation was graded according to the German program for disease management guidelines. Consensus was achieved using a multi-step nominal group procedure. RESULTS: The short-term use of amitriptyline is strongly recommended (grade A) and the short-term use of fluoxetine und duloxetine is recommended (grade B). CONCLUSIONS: The recommendations regarding pharmacological treatment of FMS are limited by the short duration of the RCT, the lack of follow-ups and absence of cost-effectiveness studies.

Köllner V, Bernardy K, Sommer C, Häuser W. · Fachklinik für Psychosomatische Medizin, MediClin Bliestal Kliniken, Blieskastel. · Dtsch Med Wochenschr. · Pubmed #19603382 No free full text.

Abstract: The meaningfulness of the term fibromyalgia syndrome (FMS), possible diagnostic criteria, and the therapeutic procedure, were for a long time points of contention between different professional associations. In an interdisciplinary S3 guideline on the definition, pathophysiology, diagnosis and therapy of FMS, it has now been possible to work out a consensus that is accepted by all involved professional associations and patient representatives on the basis of the available evidence. The most important results for clinical practice are presented and discussed here using case examples. The number of FMS patients in Germany is estimated to lie at 1.6 million (2% of the population), and 80-90% of those affected are women. FMS is classified under the functional somatic syndromes of the diseases of the musculoskeletal system and of the connective tissue (ICD 10 M 79.7). Comorbidities with other functional somatic syndromes and mental disorders are frequent. The clinical diagnosis of an FMS can ensue both by examining the tender points and also based on symptoms. Basic therapy includes elucidation and psychoeducation, aerobic endurance training adapted to the individual performance capability, operant behavioural therapy, and as a drug-based therapy option, amitriptyline 25-50mg/d (all level of evidence 1a). A graded therapeutic procedure which includes the patients in the decision-making is recommended.

Uçeyler N, Häuser W, Sommer C. · University of Würzburg, Würzburg, Germany. · Arthritis Rheum. · Pubmed #18759260 No free full text.

Abstract: OBJECTIVE: To systematically review the efficacy of treatment of fibromyalgia syndrome (FMS) with antidepressants. METHODS: We screened Medline, PsychINFO, SCOPUS, and the Cochrane Library databases (through October 2007) and the reference sections of original studies, meta-analyses, and evidence-based guidelines and recommendations on antidepressants in FMS. Randomized controlled trials (RCTs) on the treatment of FMS with antidepressants were analyzed. Inclusion criteria, study characteristics, quality, and all outcome measures were investigated. RESULTS: Twenty-six of 167 studies were included. The main outcome variables reviewed were pain, fatigue, sleep, depressiveness, and quality of life. Amitriptyline, studied in 13 RCTs, was efficient in reducing pain with a moderate magnitude of benefit (pain reduction by a mean of 26%, improvement in quality of life by 30%). Selective serotonin reuptake inhibitors (SSRIs) were studied in 12 RCTs, which also showed positive results, except for 2 studies on citalopram and 1 on paroxetine. Three RCTs on the dual serotonin and noradrenaline reuptake inhibitors (SNRIs) duloxetine and milnacipran and 1 of the 2 RCTs using the monoamine oxidase inhibitor moclobemide reported a positive result. The longest study duration was 12 weeks. CONCLUSION: Amitriptyline 25-50 mg/day reduces pain, fatigue, and depressiveness in patients with FMS and improves sleep and quality of life. Most SSRIs and the SNRIs duloxetine and milnacipran are probably also effective. Short-term treatment of patients with FMS using amitriptyline or another of the antidepressants that were effective in RCTs can be recommended. Data on long-term efficacy are lacking.

Häuser W, Bernardy K, Uçeyler N, Sommer C. · Department of Internal Medicine, Klinikum Saarbrücken, Winterberg 1, D-66119 Saarbrücken, Germany. · JAMA. · Pubmed #19141768 links to  free full text

Abstract: CONTEXT: Fibromyalgia syndrome (FMS) is a chronic pain disorder associated with multiple debilitating symptoms and high disease-related costs. Effective treatment options are needed. OBJECTIVES: To determine the efficacy of antidepressants in the treatment of FMS by performing a meta-analysis of randomized controlled clinical trials. DATA SOURCES: MEDLINE, PsycINFO, Scopus, and the Cochrane Library databases were searched through August 2008. Reference sections of original studies, meta-analyses, and reviews on antidepressants in FMS were reviewed. STUDY SELECTION: Randomized placebo-controlled trials with tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs) were analyzed. DATA EXTRACTION AND DATA SYNTHESIS: Two authors independently extracted data. Effects were summarized using standardized mean differences (SMDs) by a random-effects model. RESULTS: Eighteen randomized controlled trials (median duration, 8 weeks; range, 4-28 weeks) involving 1427 participants were included. Overall, there was strong evidence for an association of antidepressants with reduction in pain (SMD, -0.43; 95% confidence interval [CI], -0.55 to -0.30), fatigue (SMD, -0.13; 95% CI, -0.26 to -0.01), depressed mood (SMD, -0.26; 95% CI, -0.39 to -0.12), and sleep disturbances (SMD, -0.32; 95% CI, -0.46 to -0.18). There was strong evidence for an association of antidepressants with improved health-related quality of life (SMD, -0.31; 95% CI, -0.42 to -0.20). Effect sizes for pain reduction were large for TCAs (SMD, -1.64; 95% CI, -2.57 to -0.71), medium for MAOIs (SMD, -0.54; 95% CI, -1.02 to -0.07), and small for SSRIs (SMD, -0.39; 95% CI, -0.77 to -0.01) and SNRIs (SMD, -0.36; 95% CI, -0.46 to -0.25). CONCLUSION: Antidepressant medications are associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in patients with FMS.

Uçeyler N, Offenbächer M, Petzke F, Häuser W, Sommer C. · Department of Neurology, University of Würzburg Germany. · Neuropsychiatr Dis Treat. · Pubmed #18830399 links to  free full text

Abstract: Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain, tender points, fatigue, and sleep disturbance. FMS leads to high disability levels, poor quality of life, and extensive use of medical care. Effective pharmacological treatment options are rare, and treatment effects are often of limited duration. Duloxetine is a new selective serotonin and norepinephrine reuptake inhibitor that is licensed for the treatment of pain in diabetic neuropathy. So far two randomized, placebo-controlled trials have investigated the short-term safety and efficacy of duloxetine 60 mg/day and 120 mg/day in patients suffering from FMS over a period of 12 weeks. Both dosages were superior to placebo in pain relief, and improvement in quality of life and depressive symptoms. The analgesic effect was largely independent of the antidepressant action of duloxetine. The higher dose of 120 mg/day further reduced the tender point count and elevated the tender point pain thresholds. Only mild to moderate adverse effects were reported. Duloxetine 60 mg/day and 120 mg/day has proven to be beneficial in the treatment of FMS symptoms. As true for other antidepressants further studies are needed to assess the long-term efficacy and safety of duloxetine as an additional pharmacological treatment option in FMS.

Uçeyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C. · Julius-Maximilians Universität, Wurzburg, Germany. · Arthritis Rheum. · Pubmed #16871547 links to  free full text

Abstract: OBJECTIVE: The term chronic widespread pain refers to a group of painful diseases of poorly understood pathophysiology. One major subgroup is fibromyalgia (FM), as defined by the criteria of the American College of Rheumatology. Among other hypotheses, a potential pathophysiologic role of cytokines in chronic widespread pain has been proposed. We undertook this study to investigate whether cytokine profiles differ in patients with chronic widespread pain and controls. METHODS: We analyzed cytokine expression patterns in 40 patients with chronic widespread pain (26 of whom had FM), 40 age- and sex-matched healthy controls, and an additional 15 patients with chronic widespread pain who were recruited from a different center. Expression of messenger RNA (mRNA) for interleukin-2 (IL-2), IL-4, IL-8, IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) in peripheral blood was analyzed using quantitative real-time polymerase chain reaction (PCR). Serum protein levels were measured by enzyme-linked immunosorbent assay. RESULTS: We found significantly lower relative gene expression (P < 0.0001 for IL-4; P = 0.03 for IL-10) and lower levels of serum protein concentrations (P < 0.0001 for IL-4; P = 0.04 for IL-10) of the Th2 cytokines IL-4 and IL-10 in patients with chronic widespread pain than in the control group. This finding was corroborated in an additional group of 15 patients with chronic widespread pain. There were no significant differences between the groups in levels of mRNA for IL-2, IL-8, TNFalpha, or TGFbeta1. Protein data paralleled the real-time PCR results. CONCLUSION: Chronic widespread pain is associated with a lack of antiinflammatory and analgesic Th2 cytokine activity, which may contribute to its pathogenesis.