[Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. / Medikamentöse Therapie des Fibromyalgiesyndroms. Systematische Übersicht und Metaanalyse.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder. Strong opioids are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Non pharmacological treatments in fibromyalgia.

Fibromyalgia is a complex syndrome associated with significant impairment in quality of life and function and with substantial financial costs. Once the diagnosis is made, providers should aim to increase patients' function and minimize pain. Fibromyalgia patients frequently use alternative therapies, strongly indicating both their dissatisfaction with and the substantial ineffectiveness of traditional medical therapy, especially pharmacological treatments. At present, pharmacological treatments for fibromyalgia have a rather discouraging cost/benefit ratio in terms of poor symptom control and high incidence of side effects. The interdisciplinary treatment programs have been shown to improve subjective pain with greater success than monotherapy. Physical therapies, rehabilitation and alternative therapies are generally perceived to be more "natural," to have fewer adverse effects, and in some way, to be more effective. In this review, physical exercise and multimodal cognitive behavioural therapy are presented as the more accepted and beneficial forms of nonpharmacological therapy.

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

[What's new in the therapy of fibromyalgia?]. / Was gibt es Neues in der Therapie der Fibromyalgie?

Modern management of fibromyalgia (FM) requires a holistic approach, which includes nonpharmacologic strategies (both exercise and behavioral strategies) and pharmacologic treatment. Despite only partial effects in some patients, tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal antiinflammatory drugs, analgesics and opioids are in use. The use of antiepileptic drugs and antispasticity agents is mainly supported by anecdotal data. Three other classes of agents are currently thought to have useful potentials. N-methyl-D-aspartate-(NMDA-)mediated neurotransmission may play an important role in mediating wind-up and related phenomena in pain pathways. Recent studies have demonstrated that NMDA receptor antagonists improve pain symptoms in FM. But a poor side effect profile represents a significant problem. Cerebrospinal fluid substance P concentrations are significantly elevated in FM patients, but the analgesic potential of neurokinin-1 (NK1) receptor antagonists did not meet early expectations. Tropisetron, a 5-HT3 receptor antagonist, was tested in a multicenter, double-blind, randomized, placebo-controlled trial including 403 patients. In those receiving 5 mg tropisetron, 39.2% fulfilled the response criterion (pain reduction 35%) as compared to 26.2% in the placebo group (p=0.033). On 10 and 15 mg, the responder rates were smaller and statistically not significant. A total of 78 responders to therapy were followed up for 12 months. After the end of treatment, pain intensity rose within one month in all 4 groups. Patients having received 5 or 10 mg showed a less pronounced increase in pain. In addition, even 12 months after stopping treatment, pain was still markedly below baseline levels in the 5 and 10 mg groups.

Experimental studies on the intestinal uptake of organic and inorganic magnesium and potassium compounds given alone or simultaneously.

The peroral administration of magnesium and potassium compounds in effective doses (ED50) to rats yielded the following results: 1. Magnesium or potassium given as chlorides are significantly better absorbed than the corresponding aspartates. 2. In the presence of aspartate in higher concentrations the absorption of both magnesium and potassium is inhibited to a certain degree. 3. Increasing amounts of chloride cannot abolish the inhibitory effect of aspartate on potassium absorption, in contrast magnesium, which, in the presence of aspartate is better taken up when chloride is provided. 4. High concentrations of magnesium may perhaps impede the uptake of potassium to a small degree but not vice versa. 5. Magnesium losses from the body--induced by treatment with 9-alpha-fluorocortisol-acetate--can be effectively substituted by peroral administration of chloride-containing magnesium compounds over a reasonable time. The simultaneously occurring loss of potassium cannot be corrected correspondingly by potassium supplements.

The effect of metacaine (MS-222) on the activity of the efferent and afferent nerves in the teleost lateral-line system.

1. Free-swimming fish (Tilapia leucosticta and Rutilus rutilus) were used to determine threshold concentrations required for general anesthesia with metacaine (MS-222). The criterion for anesthesia was reached at a concentration of 1:1500 (w/w) with both fish, although the symptoms were somewhat more pronounced in Rutilus. 2. Recordings of efferent spontaneous activity in the lateral-line nerve were used as a measure of the central effect of metacaine during administration in the respiratory stream, as compared with respiration of fresh water. The reduction of activity at the end of a 3-min exposure to the drug was 70%. 3. Maximum recovery (90% of the initial activity) was reached after 30 min application of fresh water. 4. The various efferent impulse types were differentially affected by the anesthetic. 5. Direct recordings from sound-sensitive neurons in the medulla confirm the strong central effect of metacaine. 6. Irrigation of the lateral-line system with anesthetic solution also produced a reduction in afferent spontaneous activity; there was a distinct peripheral effect even at the threshold concentration. 7. Reactions of trigeminal nerve fibers to mechanical stimulation of the skin were reduced after application of a metacaine solution to the skin. This finding confirms the local anesthetic effect of the drug. 8. The anesthetic solution at a given concentration had a greater effect on the CNS than on the peripheral receptors. 9. The implications of the results with respect to the risk of misjudging the depth of general anesthesia are discussed. 10. Because of the complexity of its anesthetic efficacy, it is recommended that metacaine not be used for neurophysiological investigations, but rather that the animals be immobilized by means of muscle relaxants.