Interventions strongly supported by evidence (systematic reviews)
Balneo- and spa therapy
Cognitive behavioral therapy
Multicomponent treatment programs
Interventions supported by evidence (at least two RCT with consistent results)
Commonly used interventions currently unproven (only one RCT with low quality, RCTs with conflicting results or no RCT available)
Body awareness therapy
Muscle relaxants other than cyclobenzaprine
Tender point injections
Interventions strongly refuted by evidence (systematic reviews)
Biofeedback as single intervention
Relaxation therapy as single intervention for an association of antidepressants with improved health-related quality of life (HRQOL) (SMD -0.31, 95% CI -0.42 to -0.20). Effect sizes for pain reduction were large for tricyclic antidepressants (TCA) (SMD -1.64, 95% CI -2.57 to -0.71), medium for MAOI (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).
McVeigh et al.  systematically reviewed 10 RCT with balneo- or spa therapy or pooled-based exercises. Improvements were demonstrated in pain, health status, anxiety, fatigue, in addition to function and aerobic capacity. However, for the most part, improvements tended to be shor-lived.
Tofferi et al.  included five RCT with cycloben-zaprine, a muscle relaxant with additional profile of a TCA, in their meta-analysis. The odds ratio (OR) for a global improvement was 3.0 (95% CI 1.6-5.6). Cyclobenzaprine is not licensed in most European countries.
Cognitive behavioral therapy (CBT) The German FMS guideline group reviewed 14 RCT on CBT. Most studies lasted between 6 and 15 weeks, and most therapies comprised 6-30 hours of intervention. Twelve of the 14 studies found a superiority of CBT in most outcomes at the end of the therapy. Nine of the 14 studies performed follow-ups and 5/9 studies reported a persistant reduction of FMS symptoms after 6-24 months . Twenty-two out of 33 relevant studies investigating 1209 subjects could be meta-ana-lyzed. CBT had large effects on pain, self-efficacy and disability only at follow-up. Hypnotherapy has a large effect on the improvement of self-efficacy pain and a medium effect on the improvement of pain post treatment and at follow-up .
Busch and co-workers  systematically reviewed 34 studies. Meta-analysis of six studies provided moderate-quality evidence that aerobic-only exercise training at American College of Sports Medicine-recommended intensity levels has positive effects on global well-being (SMD 0.49, 95% CI 0.23-0.75) and physical function (SMD 0.66, 95% CI 0.41-0.92) and possibly on pain
(SMD 0.65, 95% CI -0.09 to 1.39). Strength and flexibility remain underevaluated; however, strength training may have a positive effect on FMS symptoms.
Multicomponent treatment (MT) programs There is no internationally accepted definition of mul-ticomponent therapy. The existing systematic reviews on MT agree that MT should include at least one educational or other psychologic therapy and at least one exercise therapy [67, 78]. The German FMS guideline group meta-analyzed 9/14 RCT, with 1119 subjects with a median treatment time of 24 hours included in the meta-analysis. There is strong evidence that MT reduces pain (SMD -0.37, 95% CI -0.62 to -0.13), fatigue (WMD -0.85, 95% CI -1.50 to -0.20), depressive symptoms (SMD -0.67, 95% CI -1.08 to -0.26) and limitations of HRQOL (SMD -0.59, 95% CI -0.90 to -0.27) and improves self-efficacy pain (SMD 0.54, 95% CI 0.26-0.82) and physical fitness (SMD 0.30, 95% CI 0.02-0.57) post treatment. There is no evidence of the efficacy of MT on pain, fatigue, sleep disturbances, depressive symptoms, HRQOL and self-efficacy pain in the long term. There is strong evidence that the positive effects on physical fitness (SMD 0.30, 95% CI 0.09-0.51) can be maintained in the long term (median follow-up 7 months) .
In a meta-analysis of four RCTs with PGB and one RCT with gabapentin with a parallel design there was a strong evidence for the reduction of pain (SMD -0.28, 95% CI -0.36 to -0.20; P < 0.001), improved sleep (SMD -0.39, 95% CI -0.48 to -0.39; P < 0.001), and improved health-related quality of life (HRQOL) (SMD -0.30, 95% CI -0.46 to -0.15; P < 0.001), but not for depressed mood (SMD -0.12, 95% CI -0.30 to 0.06; P = 0.18). There was strong evidence for a not substantial reduction of fatigue (SMD = -0.16, 95% CI -0.23 to -0.09, P < 0.001) and of anxiety (SMD = -0.18, 95% CI -0.27 to -0.10). The external validity was limited because patients with severe somatic and mental disorders were excluded .
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