We used a qualitative synthesis of the scientific evidence and consensus techniques that captures the agreement of experts based on their clinical experience and the scientific evidence7.

We took the following steps in drafting this document:

• 1

  Creation of the working group. A multidisciplinary working group was formed consisting of 5 rheumatologists who are members of the SER, a family doctor, a psychologist, a psychiatrist, a nurse, and a patient with FM. The rheumatologists were chosen through an open call to all SER members. The Committee on Clinical Practice Guidelines (CPG) and SER Recommendations assessed the curriculum vitae of all applicants according to objective criteria of their contribution to the knowledge of FM, mainly through participation in publications in journals of impact in the last 5 years.

Each of the participants was endorsed by their society to participate in this document. The clinical and methodological aspects were coordinated, respectively, by one of the rheumatologists, as principal investigator (PI), and a methodology specialist, who is a technician from the Research Unit (RU) of the SER.

• 2

  Identification of key areas. All members of the working group were involved in structuring the document and establishing the contents and key aspects. First, the clinical research questions that could have the most impact in providing information on the management of FM were identified. It was then determined which of these needed to be answered by formulating a patient, intervention, comparison, outcome (PICO) question. The setting, perspective, intervention, comparison, evaluation (SPICE) format was also used to identify qualitative evidence to provide information from the “patient perspective”. The methodology to follow in the process of drafting the recommendations was also defined.

• 3

  Literature search. A literature search was carried out in the following databases: Pubmed (MEDLINE), EMBASE (Elsevier), Cochrane Library (Wiley Online), Cinhal (EBSCOhost) and PsycInfo. The searches were closed with dates of July 2019. A later search update was carried out in April 2020. The process was completed with a manual search of references and conference posters and abstracts considered of interest by the reviewers and experts.

• 4

  Analysis and synthesis of the scientific evidence. Several rheumatologists from the SER evidence review group and methodologists from the RU were in charge of systematically reviewing the available scientific evidence. The overall level of scientific evidence was assessed using the Scottish Intercollegiate Guidelines Network levels of evidence7 for the PICO questions (Appendix B Annex 1, Supplementary data) and the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research)8 approach for qualitative evidence from the SPICE questions (Appendix B Annex 2, Supplementary data). Formulation of the recommendations. After the critical reading, the PI and members of the expert group proceeded to formulate specific recommendations based on the scientific evidence. In the case of quantitative evidence, this was based on “formal evaluation” or “reasoned judgement”, summarising the evidence for each of the clinical questions beforehand. The quality, quantity and consistency of the scientific evidence, the generality of the results, their applicability and their clinical impact were also considered. The Scottish Intercollegiate Guidelines Network system7 (Appendix Annex 1, Supplementary data) was used to grade the recommendations. Again, the GRADE-CERQual8 approach was used for the evidence from qualitative research (Appendix B Annex 2, Supplementary data). The recommendations are divided into four main areas: diagnosis and prognosis of FM, ineffective and unsafe therapeutic interventions, FM patient education and information, and training of FM professionals.

• 5

  External review. At the end of the previous phase, a final draft of the document was prepared and sent for independent external review to professionals selected for their knowledge of FM to increase the external validity of the document and ensure the accuracy of the recommendations.

• 6

  Public exposure. This draft was then put through a process of public exposure to SER members and different interest groups (pharmaceutical industry, other scientific societies, and patient associations) to gather their assessment and scientific argumentation of the methodology or recommendations.

• 7

  Scientific societies. The scientific societies involved in drafting this guideline, represented by members of the drafting group, are the Spanish Society of Rheumatology (SER), the Spanish Society of Primary Care Physicians (SEMERGEN), the Spanish Society of Clinical and Health Psychology (SEPCyS), the General Council of Official Nursing Associations of Spain (CGE), and the Spanish Society of Fibromyalgia and Chronic Fatigue (SEFIFAC).

The document includes the recommendations made, subdivided into the different areas mentioned above.

The complete recommendations document and patient information is available on the SER website.

Which pharmacological interventions and/or combinations of benzodiazepines, non-steroidal anti-inflammatory drugs (NSAIDs), Z-drugs, anticonvulsants, tramadol, and major opioids have not shown efficacy/effectiveness and safety in the treatment of fibromyalgia?

Recommendation 6: There are insufficient studies to recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain in adult patients with fibromyalgia (Grade A recommendation).

Recommendation 7: The drafting group does not recommend the use of major opioids to treat pain in patients with fibromyalgia due to insufficient evidence of their effectiveness and the possible risk of adverse effects (Recommendation grade √).

Recommendation 8: No pharmacological combination can be recommended or discouraged in the treatment of adult patients with fibromyalgia, in the absence of sufficient evidence on their efficacy and safety (Recommendation grade C).

Recommendation 9: The use of anticonvulsants such as lacosamide or lamotrigine to reduce pain is not recommended due to lack of efficacy (Recommendation grade B).

There is no evidence of the effectiveness of other antiepileptic drugs such as carbamazepine, clonazepam, phenytoin or valproate, or the existing evidence on their effectiveness is insufficient to make a recommendation for or against (Recommendation grade √).

Recommendation 10: The drafting group does not recommend the chronic use of benzodiazepines or Z-drugs in patients with fibromyalgia due to lack of evidence on effectiveness and the possible risk of addiction and other adverse effects (Recommendation grade √).

The data on pharmacological treatment in patients with FM show poor results35, with 33% improvement in the severity of the variables analysed in only a third of patients36.

Antidepressants such as tricyclics and serotonin and norepinephrine reuptake inhibitors, gabapentinoids such as pregabalin and gabapentin, and analgesics such as tramadol at low doses have shown efficacy in randomised clinical trials; these are the drugs recommended by the scientific societies5.

However, other drugs for which there is no solid evidence of efficacy in FM are frequently added, making combined drug treatment with more than three drugs a reality in 30% of patients37, and 40% of patients are using five or more drugs (polymedication)38.

NSAIDs are very commonly used in patients with FM, in more than 40%39. Their use should be rationed due to potential adverse gastrointestinal, renal, and cardiovascular effects40.

The use of opioids for the treatment of chronic non-cancer pain has increased dramatically in recent decades41. Major opioids, i.e., more potent than tramadol, are used by 27% of these patients42. Therefore, the possibility of side effects and significant interactions with other drugs is not negligible and could aggravate the clinical manifestations of the disease. Thus, for example, in patients with FM who are major opioid users, it has been shown that only discontinuing opioids results in an improvement in the clinical manifestations41.

The drugs most frequently used by FM patients include NSAIDs, benzodiazepines, Z-drugs, some anticonvulsants, and major opioids. The most used drugs, or combinations of drugs, that have not demonstrated efficacy or safety in these patients need to be assessed.

The evidence found for this question was limited. Only one SR was found that evaluates the efficacy and safety of NSAIDs, another SR that evaluates anticonvulsants, another that evaluates pharmacological combinations, and finally one that evaluates oxycodone43–57. Studies were found that do not meet the inclusion criteria, but may provide additional information on other aspects of the diagnosis5,45.

Full information on the results obtained from the evidence review is available on the SER website (Appendix B Table 2, Additional material).

It is particularly important to detect drugs, or drug combinations that are not effective for FM, as the side effects of many drugs aggravate the clinical manifestations of the disease itself.

Thus, the evidence found on the ineffectiveness of NSAIDs in the treatment of pain in patients with FM should lead to their being discontinued. Although there is insufficient evidence to advise for or against the use of the major opioids in the treatment of FM, the drafting group considers that they should not be used due to the serious adverse effects described with this type of drug.

The drafting group considers that it is always important to avoid polymedication in any patient, but even more so in patients with FM as these patients are very often polymedicated.

Which complementary alternative medicine (CAM) interventions have not shown efficacy/effectiveness and safety in the treatment of fibromyalgia?

Recommendation 11: although statistically significant results on the efficacy of transcranial electrical stimulation or transcranial magnetic stimulation have been observed in some studies, the drafting group considers that as these techniques are of limited clinical relevance, they cannot be recommended in the treatment of patients with fibromyalgia (Recommendation grade B).

Recommendation 12: There is insufficient evidence to recommend the use of TENS in the treatment of fibromyalgia until trials of methodological quality demonstrate its efficacy (Recommendation grade B).

Recommendation 13: More studies are needed that assess the efficacy of cannabinoids (nabilone) in improving pain and quality of life to recommend their use in patients with fibromyalgia (Recommendation grade √).

Recommendation 14: Although in some studies it appears that nabilone may be more effective than amitriptyline in improving sleep quality, it is not recommended for use in patients with fibromyalgia due to a higher frequency of adverse effects (Recommendation grade √).

Recommendation 15: Homeopathy, chiropractic, osteopathy, and manipulations are not recommended in the treatment of fibromyalgia, due to the lack of studies confirming the efficacy and safety of these techniques (Recommendation grade √).

Recommendation 16: There is insufficient evidence to recommend pulsed electromagnetic therapy in the treatment of fibromyalgia (Recommendation grade B).

Recommendation 17: there is insufficient evidence to recommend relaxation monotherapy in the treatment of fibromyalgia, due to the limited benefit obtained in the improvement of pain and quality of life (Recommendation grade D).

Recommendation 18: although results of short-term improvement in certain clinical variables have been observed in some studies with therapeutic massage, as they are so few and of doubtful clinical significance, its use in the treatment of patients with fibromyalgia cannot be recommended (Recommendation grade B).

Recommendation 19: There is insufficient evidence to recommend the use of Reiki or touch therapy in the treatment of patients with fibromyalgia (Recommendation grade B).

Recommendation 20: Dry needling is not recommended in patients with fibromyalgia, due to the lack of evidence and the possibility of frequent side effects (Recommendation grade √).

Recommendation 21: there is insufficient evidence to recommend hyperbaric oxygen or ozone therapy (Recommendation grade √).

The limited efficacy and adverse effects of drugs limit their use, and therefore patients with FM often resort to CAM therapies. In this regard, Perry58 reports that 90% of patients have used some form of CAM for symptom control. CAM is defined as “… diagnosis, treatment, and/or prevention which complements mainstream medicine by contributing to a common whole, satisfying a demand not met by orthodoxy, or diversifying the conceptual frameworks of medicine”58.

Previous SRs have established the CAM interventions that have been shown to be effective in the treatment of FM59. The current aim is to update the search for available evidence to assess the safety of CAM interventions and to establish those that are not effective or efficacious.

The evidence identified for the wide range of existing treatments categorised as complementary and alternative medicine has been divided into the following groups: 1) non-invasive brain stimulation; 2) transcutaneous stimulation; 3) cannabis; 4) homeopathy; 5) chiropractic and osteopathy; 6) electromagnetic therapy; 7) relaxation/training; 8) massage; 9) energy therapies; 10) dry needling; and 11) ozone therapy/hyperbaric oxygen60–98. Studies were found that do not meet the inclusion criteria, but they may provide additional information on other aspects of the diagnosis99–102.

Full information on the results of the evidence review is available on the SER website.

The drafting group considers that within the CAM interventions assessed, those related to non-invasive brain stimulation have the most consistent results. However, in both electrical stimulation and magnetic stimulation, there is significant heterogeneity in the methodology for applying the interventions.

The work on TENS is less consistent. In general, the studies have major risks of bias and small sample sizes, and the results show that TENS is not effective for pain if compared to no treatment, but is effective compared to physical activity, superficial heat, hydrotherapy, or SAMe.

The evaluation of cannabinoids focused on nabilone and shows quite consistent results on pain relief and sleep, but not on mood. There is also considerable consistency regarding the low safety of nabilone, showing significant side effects.

The studies on homeopathy, chiropractic and osteopathy are very heterogeneous and with small sample sizes, and therefore no conclusions could be drawn.

Regarding relaxation methods, massage or energy therapies, the SRs identified include only one RCT on the subject and vary greatly in methodology and in the evaluation of the results.

The drafting group considers that the results of the studies of the various CAM interventions assessed do not mean they should be applied directly in our public health system as no clear efficacy has been demonstrated. They are more likely to be used in the field of private medicine, although this in turn encourages a greater risk of professional intrusion in the treatment of patients with FM.

The CAM interventions studied have an acceptable safety role, except for nabilone and chiropractic. This facilitates their use, even if there is no evidence of their efficacy.

The analysis in this review supports professionals who care for FM patients in advising or discouraging certain CAM interventions, based on efficacy, safety, and cost-effectiveness.

Which surgical interventions have not shown efficacy/effectiveness or safety in the treatment of fibromyalgia?

Recommendation 22: In patients with fibromyalgia with a well-established indication for total knee arthroplasty, it is recommended that the intervention be performed. However, they should be monitored postoperatively given the possibility of a greater number of medical and surgical complications (Recommendation grade D).

Recommendation 23: It is not recommended that arthroscopic or subacromial shoulder decompression surgery in patients with FM be discouraged a priori. However, given the possibility of poorer recovery and patient satisfaction following the surgery, the indication should be closely reviewed, alternatives sought, and the patient informed (Recommendation grade C).

Recommendation 24: It is recommended that indications for spinal arthrodesis surgery in patients with fibromyalgia be carefully assessed for the possibility of postoperative medical complications (Recommendation grade C).

Recommendation 25: Careful assessment of postoperative opioid use is recommended in fibromyalgia patients undergoing any type of surgery (Recommendation grade D).

Recommendation 26: In women undergoing breast cancer surgery, preoperative assessment for fibromyalgia is recommended to predict postoperative neuropathic pain (Recommendation grade D).

Recommendation 27: The drafting group of this document recommends preoperative assessment for fibromyalgia in people with chronic pain who are to undergo any type of surgery, given the possibility of a greater number of complications and higher opioid use in the postoperative period (Recommendation grade √).

FM is known to affect pain processing mechanisms in the nociceptive system103, is associated with high analgesic consumption104, and has increased comorbidities105 coexisting with other musculoskeletal or visceral diseases106, which may contribute to pain. Patients with FM often require surgical intervention with the risk of unsatisfactory outcomes that may be different to those of people without FM.

The aim of this SR is to evaluate the safety and efficacy of surgery in musculoskeletal and visceral processes when FM is an associated comorbidity.

The scientific evidence found on the indication for surgical interventions in patients with FM comes solely from observational studies107–123. Studies were found that do not meet the inclusion criteria, but may provide additional information on other aspects of the diagnosis124–127.

The results obtained were organised into two different main areas: efficacy and safety. Full information on the results obtained from the review of the evidence is available on the SER website.

The different studies in patients with FM are highly consistent in the similarity of surgical outcomes with patients without FM. However, they are also significantly consistent in that the degree of patient satisfaction after surgery is lower and that the number of complications, both medical and surgical, is higher in patients with FM.

The drafting group considers that surgeons can easily apply the recommendations made in this document to our healthcare system, as only the possibility that the patient has an associated FM should be considered before surgery is performed. Although the focus here was work related to musculoskeletal surgery, the drafting group believes it is highly likely that these recommendations can be generalised to any surgical procedure.

The most relevant aspect of these recommendations is that their application may result in fewer postoperative complications. This would therefore also reduce the economic costs associated with surgery.

For the drafting group, it is important to emphasise that the aim of these recommendations is to ensure that indications for surgery are always correctly established in a patient with FM for them to benefit from the surgery and avoid unnecessary post-surgical complications.