As with many other medically unexplained syndromes, there is no universally accepted treatment or cure for<unk> , and treatment typically consists of symptom management and improving patient quality of life. A personalized, multidisciplinary approach to treatment that includes both non-pharmacologic and pharmacologic therapy and begins with effective patient education is most beneficial. Developments in the understanding of the pathophysiology of the disorder have led to improvements in treatment, which include prescription medication, behavioral intervention, and exercise. A number of associations have published guidelines for the diagnosis and management of<unk> . The European League Against Rheumatism (EULAR; 2017) recommends a multidisciplinary approach, allowing a quick diagnosis and patient education. The recommended initial management should be non-pharmacological, later pharmacological treatment can be added. The European League Against Rheumatism gave the strongest recommendation for aerobic and strengthening exercise. Weak recommendations were given to a number of treatments, based on their outcomes. Qigong, yoga, and tai chi were weakly recommended for improving sleep and quality of life. Mindfulness was weakly recommended for improving pain and quality of life. Acupuncture and hydrotherapy were weakly recommended for improving pain. A weak recommendation was also given to psychotherapy. It was more suitable for patients with mood disorders or unhelpful coping strategies. Chiropractic was strongly recommended against, due to safety concerns. Some medications were weakly recommended for severe pain (duloxetine, pregabalin, tramadol) or sleep disturbance (amitriptyline, cyclobenzaprine, pregabalin). Others were not recommended due to a lack of efficacy (nonsteroidal anti-inflammatory drugs, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors). Growth hormone, sodium oxybate, opioids and steroids were strongly recommended against due to lack of efficacy and side effects. The guidelines published by the Association of the Scientific Medical Societies in Germany inform patients that self-management strategies are an important component it managing the disease. The Canadian Pain Society also published guidelines for the diagnosis and management of<unk> . Exercise Exercise is the only<unk>  treatment which has been given a strong recommendation by the European Alliance of Associations for Rheumatology (EULAR). There is strong evidence indicating that exercise improves fitness and sleep and may reduce pain, fatigue and quality of life for people with<unk> . Several studies have also found that exercise can improve cognitive functioning. Exercise has an added benefit in that it does not cause any serious adverse effects. Exercise may diminish<unk>  symptoms through a number of hypothesized biological mechanisms. Exercise may improve pain modulation through serotoninergic pathways. It may reduce pain by altering the hypothalamic-pituitary-adrenal axis and reducing cortisol levels. It also has anti-inflammatory effects that may improve<unk>  symptoms. Aerobic exercise can improve muscle metabolism and pain through mitochondrial pathways. When comparing different exercise programs, aerobic exercise is capable of modulating the autonomic nervous function of<unk>  patients, whereas resistance exercise does not show such effects. Meditative exercise seems preferable for improving sleep, with no differences between resistance, flexibility and aquatic exercise in their favorable effects on fatigue. Despite its benefits, exercise is a challenge for patients with<unk> , due to the chronic fatigue and pain they experience. They perceive it as more effortful than healthy adults. Exercise may intimidate them, in fear that they will be asked to do more than they are capable of. They may also feel that those who recommend or deliver exercise interventions do not fully understand the possible negative impact of exercise on fatigue and pain. This is especially true for non-personalized exercise programs. Adherence is higher when the exercise program is recommended by doctors or supervised by nurses. A recommended approach to a graded exercise program begins with small, frequent exercise periods and builds up from there. Aerobic Aerobic exercise for<unk>  patients is the most investigated type of exercise. It includes activities such as walking, jogging, spinning, cycling, dancing and exercising in water. A 2017 cochrane summary concluded that aerobic exercise probably improves quality of life, slightly decreases pain and improves physical function and makes no difference in fatigue and stiffness. A 2019 meta-analysis showed that exercising aerobically can reduce autonomic dysfunction and increase heart rate variability. This happens when patients exercise at least twice a week, for 45–60 minutes at about 60%-80% of the maximum heart rate. Aerobic exercise also decreases anxiety and depression and improves the quality of life. Flexibility Combinations of different exercises such as flexibility and aerobic training may improve stiffness. However, the evidence is of low-quality. It is not clear if flexibility training alone compared to aerobic training is effective at reducing symptoms or has any adverse effects. Resistance In resistance exercise, participants apply a load to their body using weights, elastic band, body weight or other measures. Two meta-analyses have shown that resistance training can reduce anxiety and depression and one found that it improves quality of life. Along with endurance and coordination, consistent low-intensity with progressive workloads have been shown to decrease the perception of pain and decrease fatigue. Because physical exercise tends to improve the physical condition, the overall quality of life is also bettered. The dosage of resistance exercise for women with<unk>  was studied in a 2022 meta-analysis. Effective dosages were found when exercising twice a week, for at least eight weeks. Symptom improvement was found for even low dosages such as 1–2 sets of 4–20 repetitions. Most studies use moderate exercise intensity of 40% to 85% one-repetition maximum. This level of intensity was effective in reducing pain. Some treatment regimes increase the intensity over time (from 40% to 80%), whereas others increase it when the participant is able to perform 12 repetitions. High-intensity exercises may cause lower treatment adherence. Meditative A 2021 meta-analysis found that meditative exercise programs (tai chi, yoga, qigong) were superior to other forms of exercise (aerobic, flexibility, resistance) in improving sleep quality. The positive effect of tai chi on sleep for people with diverse conditions has been documented in a second meta-analysis. A third met-analysis from 2019 found that in addition to improving sleep, tai chi improves pain, fatigue, depression and quality of life, for patients with<unk> . These tai chi interventions frequently included 1-hour sessions practiced 1-3 times a week for 12 weeks. Meditative exercises, as a whole, may achieve desired outcomes through biological mechanisms such as antioxidation, anti-inflammation, reduction in sympathetic activity and modulation of glucocorticoid receptor sensitivity. Aquatic Several reviews and meta-analyses suggest that aquatic training can improve symptoms and wellness in people with<unk> . Other Limited evidence suggests vibration training in combination with exercise may improve pain, fatigue, and stiffness. Medications A few countries have published guidelines for the management and treatment of<unk> . As of 2018, all of them emphasize that medications are not required, only optional. The German guidelines outlined parameters for drug therapy termination and recommended considering drug holidays after six months. Approved medications Health Canada and the US Food and Drug Administration (FDA) have approved pregabalin and duloxetine for the management of<unk> . The FDA also approved milnacipran, but the European Medicines Agency refused marketing authority. Antidepressants Antidepressants are one of the common drugs for<unk> . A 2021 meta-analysis concluded that antidepressants can improve the quality of life for<unk>  patients in the medium-term. As of 2018, the only tricyclic antidepressant (TCA) that has sufficient evidence is amitriptyline. For most people with<unk> , the potential benefits of treatment with the serotonin and noradrenaline reuptake inhibitors (SNRI) duloxetine and milnacipran and the TCAs, such as amitriptyline, are outweighed by significant adverse effects (more adverse effects than benefits), however, a small number of people may experience relief from symptoms with these medications. In addition, while amitriptyline has been used as a first line treatment, the quality of evidence to support this use and comparison between different medications is poor. Very weak evidence indicates that a very small number of people may benefit from treatment with the tetracyclic antidepressant mirtazapine, however, for most, the potential benefits are not great and the risk of adverse effects and potential harm outweighs any potential for benefit. The length of time that antidepressant medications take to be effective at reducing symptoms can vary. Any potential benefits from the antidepressant amitriptyline may take up to three months to take effect and it may take between three and six months for duloxetine, milnacipran, and pregabalin to be effective at improving symptoms. Some medications have the potential to cause withdrawal symptoms when stopping so gradual discontinuation may be warranted particularly for antidepressants and pregabalin. There is tentative evidence that the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) appear to be similar. SSRIs may be used to treat depression in people diagnosed with<unk> . Tentative evidence suggests that monoamine oxidase inhibitors (MAOIs) such as pirlindole and moclobemide are moderately effective for reducing pain. Very low-quality evidence suggests pirlindole as more effective at treating pain than moclobemide. Side effects of MAOIs may include nausea and vomiting. Central nervous system depressants Central nervous system depressants include drug categories such as sedatives, tranquilizers, and hypnotics. A 2021 meta-analysis concluded that such drugs can improve the quality of life for<unk>  patients in the medium-term.
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