Sarzi-Puttini P, Atzeni F, Mease PJ.
Chronic widespread pain: from peripheral to central evolution.
Best Pract Res Clin Rheumatol. 2011 Apr;25(2):133-9. doi: 10.1016/j.berh.2011.04.001.
Abstract/Text
Chronic pain can be classified as localised, regional or widespread, and its high prevalence in the general population seems to increase with age. The majority of cases present with musculoskeletal pain. The conditions associated with chronic widespread pain (CWP) are highly burdensome as their characteristic symptoms may include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of concomitant mood disorders. After many years of debate, it is still unclear whether CWP (central sensitisation) is an entirely explainable neurotransmitter-related process or is partially or totally due to individual cognitive experiences and evaluations. The two models (neurochemical and biopsychosocial) also affect our ability to find therapeutic answers.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Schmidt-Wilcke T, Clauw DJ.
Fibromyalgia: from pathophysiology to therapy.
Nat Rev Rheumatol. 2011 Jul 19;7(9):518-27. doi: 10.1038/nrrheum.2011.98. Epub 2011 Jul 19.
Abstract/Text
Individuals with fibromyalgia generally experience chronic widespread pain, which can be accompanied by further symptoms including fatigue, sleep disturbances, cognitive dysfunction, anxiety and depressive episodes. As the recognition and diagnosis of fibromyalgia has improved, the availability of therapeutic options for patients has increased. Furthermore, research into the neurobiological mechanisms that contribute to the chronic pain and concomitant symptoms experienced by patients with fibromyalgia has advanced our understanding of this debilitating disorder. In this Review, we aim to provide an overview of existing pathophysiological concepts. The roles of biological and psychological stress, genetic factors, and pain and sensory processing in the pathophysiology of fibromyalgia and related conditions are discussed. In addition, pharmacological treatments, including monoamine modulators, calcium channel modulators and γ-aminobutyric acid modulators, as well as nonpharmacological treatment options are considered.
Staud R.
Abnormal pain modulation in patients with spatially distributed chronic pain: fibromyalgia.
Rheum Dis Clin North Am. 2009 May;35(2):263-74. doi: 10.1016/j.rdc.2009.05.006.
Abstract/Text
Many chronic pain syndromes are associated with hypersensitivity to painful stimuli and with reduced endogenous pain inhibition. These findings suggest that modulation of pain-related information may be linked to the onset or maintenance of chronic pain. The combination of heightened pain sensitivity and reduced pain inhibition seems to predispose individuals to greater risk for increased acute clinical pain. It is unknown whether such pain processing abnormalities may also place individuals at increased risk for chronic pain. Psychophysical methods can be used for the evaluation of pain sensitivity and pain inhibition. Long-term prospective studies that could yield insight into the role of heightened pain sensitivity and pain disinhibition for the development of chronic pain disorders like fibromyalgia in the general population are lacking, however.
Valencia C, Fatima H, Nwankwo I, Anam M, Maharjan S, Amjad Z, Abaza A, Vasavada AM, Sadhu A, Khan S.
A Correlation Between the Pathogenic Processes of Fibromyalgia and Irritable Bowel Syndrome in the Middle-Aged Population: A Systematic Review.
Cureus. 2022 Oct;14(10):e29923. doi: 10.7759/cureus.29923. Epub 2022 Oct 4.
Abstract/Text
Irritable bowel syndrome (IBS) is a common pathology in middle-aged patients and a regular consultation in the gastroenterology office. The prevalence is high in females with a ratio of 2:1, and due to its multifactorial etiology, it is difficult to address the symptomatology. On the other hand, fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome also prevalent in the female population, characterized by systemic symptoms. It is proven that 28-59 % of patients with FMS develop IBS at some point in their illness; on the other hand, 32-77% of those with IBS will develop FMS. Our study aims to compile information about the pathogenesis of these diseases and highlight their common processes to target these two illnesses potentially. This systematic review comprises twenty-three studies published between 2017 and 2022, selected by electronic research with keywords and Medical Subject Headings (MESH) strategy. The articles were taken from PubMed, Pubmed Central (PMC), Medline, and Cochrane libraries and met the inclusion and exclusion criteria and the pertinent quality checklists. Of the reviewed studies, 10 were case-control, six were narrative reviews, three were systematic reviews, three were cross-sectional, and one was a cohort study. They investigated the correlation and similitudes in the pathogenic process between FMS and IBS. There are some similar mechanisms in the physiopathologies of IBS and FMS, where the immune system, especially the mast cells (MCs), along with their products, receptors, the inflammatory cells with their intermediaries, hormones, and neurotransmitters such as serotonin, act together pathologically. Also, the role of the microbiota is very important in this pathogenesis since dysbiosis alters the levels of serotonin in the body and can produce hyperstimulation of the autonomic nervous system. There are common associated factors in IBS and FMS, with evident symptoms presented in both syndromes such as fatigue, pain, hypersensitivity, depression, anxiety, and others, that could be correlated in a certain way. After this systematic review, we can conclude that the most accepted theories of the common pathogenesis are the role of serotonin and MCs with their inflammatory biomarkers, which can affect different parts of the body producing the characteristic symptomatology. Moreover, other pathogenic mechanisms such as the involvement of microbiota and dysregulation of the gut-brain axis have shown promising results, and further investigation should be made to support their role.
Copyright © 2022, Valencia et al.
Nicholas M, Vlaeyen JWS, Rief W, Barke A, Aziz Q, Benoliel R, Cohen M, Evers S, Giamberardino MA, Goebel A, Korwisi B, Perrot S, Svensson P, Wang SJ, Treede RD; IASP Taskforce for the Classification of Chronic Pain.
The IASP classification of chronic pain for ICD-11: chronic primary pain.
Pain. 2019 Jan;160(1):28-37. doi: 10.1097/j.pain.0000000000001390.
Abstract/Text
This article describes a proposal for the new diagnosis of chronic primary pain (CPP) in ICD-11. Chronic primary pain is chosen when pain has persisted for more than 3 months and is associated with significant emotional distress and/or functional disability, and the pain is not better accounted for by another condition. As with all pain, the article assumes a biopsychosocial framework for understanding CPP, which means all subtypes of the diagnosis are considered to be multifactorial in nature, with biological, psychological, and social factors contributing to each. Unlike the perspectives found in DSM-5 and ICD-10, the diagnosis of CPP is considered to be appropriate independently of identified biological or psychological contributors, unless another diagnosis would better account for the presenting symptoms. Such other diagnoses are called "chronic secondary pain" where pain may at least initially be conceived as a symptom secondary to an underlying disease. The goal here is to create a classification that is useful in both primary care and specialized pain management settings for the development of individualized management plans, and to assist both clinicians and researchers by providing a more accurate description of each diagnostic category.
Trouvin AP, Perrot S.
New concepts of pain.
Best Pract Res Clin Rheumatol. 2019 Jun;33(3):101415. doi: 10.1016/j.berh.2019.04.007. Epub 2019 May 13.
Abstract/Text
Active research is being conducted on musculoskeletal pain, and recent concepts will help clinicians and researchers to develop better approaches: -the new pain taxonomy recently has been modified with a third descriptor with the concept of nociplastic pain. -the latest International Classification of Diseases (ICD-11) includes an IASP task force that developed a new classification system for pain. In this new classification, one can differentiate primary musculoskeletal pain including fibromyalgia and low back pain and secondary musculoskeletal pain related to specific etiologies. -the concept of central sensitization in inflammatory rheumatic diseases is increasingly discussed. In these conditions, even with very active biological treatment, almost a third of patients are still complaining of persisting pain. These persisting pain states under adequate treatment, without any sign of inflammation, led researchers to look for evidence of central sensitization states.
Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.
松本美富士，前田伸治，玉腰暁子，他：線維筋痛症の臨床疫学像（全国疫学調査の結果から）．臨床リウマチ 2006；18：87-92.
松本美富士，前田伸治，玉腰暁子，他：本邦線維筋痛症の臨床疫学像解明に関する研究．厚生労働科学研究免疫アレルギー疾患予防・治療研究事業：関節リウマチの先端的治療に関する研究．平成16年度研究報告書2005；49-52.
松本美富士：線維筋痛症の疫学．Pharma Medica 2006；24：35-39.
服部政治：日本における慢性疼痛保有率．日本薬理学会誌2006；127：176-180．.
Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB.
The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.
Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140.
Abstract/Text
OBJECTIVE: To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms.
METHODS: We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale.
RESULTS: Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9).
CONCLUSION: This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.
日本線維筋痛症学会・日本医療研究開発機構線維筋痛症研究班編 線維筋痛症診療ガイドライン2017 CQ6-2線維筋痛症の診断にどの基準をもちいるか 日本医事新報社、東京、p106-110.2017.
線維筋痛症診療ガイドライン 2013版 編集 日本線維筋痛症学会ガイドライン作成委員会 5章 治療 1治療総論.
Santos Dde M, Lage LV, Jabur EK, Kaziyama HH, Iosifescu DV, Lucia MC, Fraguas R.
The association of major depressive episode and personality traits in patients with fibromyalgia.
Clinics (Sao Paulo). 2011;66(6):973-8. doi: 10.1590/s1807-59322011000600009.
Abstract/Text
INTRODUCTION: Personality traits have been associated with primary depression. However, it is not known whether this association takes place in the case of depression comorbid with fibromyalgia.
OBJECTIVE: The authors investigated the association between a current major depressive episode and temperament traits (e.g., harm avoidance).
METHOD: A sample of 69 adult female patients with fibromyalgia was assessed with the Temperament and Character Inventory. Psychiatric diagnoses were assessed with the Mini-International Neuropsychiatric Interview severity of depressive symptomatology with the Beck Depression Inventory, and anxiety symptomatology with the IDATE-state and pain intensity with a visual analog scale.
RESULTS: A current major depressive episode was diagnosed in 28 (40.5%) of the patients. They presented higher levels of harm avoidance and lower levels of cooperativeness and self-directedness compared with non-depressed patients, which is consistent with the Temperament and Character Inventory profile of subjects with primary depression. However, in contrast to previous results in primary depression, no association between a major depressive episode and self-transcendence was found.
CONCLUSIONS: The results highlight specific features of depression in fibromyalgia subjects and may prove important for enhancing the diagnosis and prognosis of depression in fibromyalgia patients.
Arnold LM, Bennett RM, Crofford LJ, Dean LE, Clauw DJ, Goldenberg DL, Fitzcharles MA, Paiva ES, Staud R, Sarzi-Puttini P, Buskila D, Macfarlane GJ.
AAPT Diagnostic Criteria for Fibromyalgia.
J Pain. 2019 Jun;20(6):611-628. doi: 10.1016/j.jpain.2018.10.008. Epub 2018 Nov 16.
Abstract/Text
Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Kanazawa T, Ito K, Yamano Y, Nakamura H, Nakajima T, Nishioka K.
The Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and the Fibromyalgia Symptom Scale: reliability and validity.
Mod Rheumatol. 2012 Feb;22(1):40-4. doi: 10.1007/s10165-011-0462-3. Epub 2011 May 10.
Abstract/Text
The aim of this study was to investigate the reliability and the validity of the Japanese version of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010-J), and its quantification scale, the Fibromyalgia Symptom Scale (FS-J). In this study, we divided patients with chronic pain without psychiatric disorders other than depression into two groups according to the 1990 ACR Diagnostic Criteria for Fibromyalgia, a fibromyalgia group and a non-fibromyalgia group (rheumatoid arthritis, osteoarthritis, and gout). Patients in both groups were assessed using the ACR 2010-J and FS-J. Seventy-seven of 94 (82%) patients in the fibromyalgia group met the ACR 2010-J, whereas 9% (4/43) of the non-fibromyalgia group did so, with a sensitivity of 82%, specificity of 91%, positive predictive value of 95%, negative predictive value of 70%, and positive likelihood ratio of 8.8. Mean total scores on the FS-J significantly differentiated the fibromyalgia from the non-fibromyalgia group. The scale had high inter-rater reliability and high internal consistency. With a cutoff score of 10, the positive likelihood ratio was 10.1. Our findings indicate that the ACR 2010-J and FS-J have high reliability and validity, and are useful for assessing fibromyalgia in Japanese populations with chronic pain. As regards the positive likelihood ratio, that of the FS-J might be suitable as a positive test.
西岡久寿樹：線維筋痛症の新しいACRの診断基準の検証について．第2回日本線維筋痛症学会抄録集．2010；p.32.
Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR preliminary diagnostic criteria for fibromyalgia.74th American College of Rheumatology Annual Scientific Meeting abstract 2010;S41.
松本美富士：多施設共同によるアメリカリウマチ学会2010診断予備基準、2011改訂基準の本邦症例での有用性検証と慢性疲労症候群併発頻度の検討：厚生労働科学研究費補助金慢性の痛み対策研究事業：線維筋痛症をモデルとした慢性疼痛機序の解明と治療法の確立に関する研究。平成25年度研究報告書2014;16-18.
Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB.
Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia.
J Rheumatol. 2011 Jun;38(6):1113-22. doi: 10.3899/jrheum.100594. Epub 2011 Feb 1.
Abstract/Text
OBJECTIVE: To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity.
METHODS: The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician's estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0-31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA).
RESULTS: The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria- patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population.
CONCLUSION: A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.
Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P.
The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee.
Arthritis Rheum. 1990 Feb;33(2):160-72. doi: 10.1002/art.1780330203.
Abstract/Text
To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.
松本美富士：膠原病・類縁疾患に伴う神経・筋障害の診断と治療 機能性リウマチ性疾患 線維筋痛症. 日本内科学会雑誌 2010; 99(8): 1837-1844.
日本線維筋痛症学会・日本医療研究開発機構線維筋痛症研究班編、線維筋痛症診療ガイドライン2017 第1部疾患の解説とトピックス 高齢者/若年者の疾患特性、日本医事新報社、東京、p35-41.2017.
Yunus MB, Masi AT.
Juvenile primary fibromyalgia syndrome. A clinical study of thirty-three patients and matched normal controls.
Arthritis Rheum. 1985 Feb;28(2):138-45. doi: 10.1002/art.1780280205.
Abstract/Text
Primary fibromyalgia syndrome (PFS) is a common and characteristic rheumatologic condition manifested by diffuse musculoskeletal aches, pains, and stiffness frequently modulated by various factors, e.g., weather, physical activity, sleep quality, and anxiety/stress, and accompanied by discrete tender points at typical soft tissue sites. Although well-recognized in adults, this entity has not been reported separately in juveniles. This study documents PFS in 33 juveniles who presented at age 17 or younger and compares their findings with those in age- and sex-matched normal control subjects. As in adult PFS patients, associated non-musculoskeletal symptoms were common, including fatigue, poor sleep, anxiety/stress, headaches, and paresthesias. Physical examination revealed multiple tender points at characteristic soft tissue sites and no objective evidence of arthritis. Routine laboratory test results were normal or negative. Juvenile PFS is often misdiagnosed. Recognition of this common rheumatologic condition in juveniles is important in order to avoid unwarranted investigations and improper management.
Yokota S, Kikuchi M, Miyamae T.
Juvenile fibromyalgia: Guidance for management.
Pediatr Int. 2013 Aug;55(4):403-9. doi: 10.1111/ped.12155.
Abstract/Text
Juvenile fibromyalgia (JFM) is a disease in which patients complain of acute and chronic severe pain, an overt primary cause for which cannot be found or surmised. Although patients with JFM mainly complain of systemic pain or allodynia in the medical interview and physical examination, the concept of the disease is the total sum of painful illness, chronic fatigue, hypothermia and many other autonomic symptoms and signs. Many issues are interacting including individual traits (personality, temperament, sensitivity, memory of pain; age: early adolescence), individual states (self-esteem, anxiety, developmental level), and external stressors (parent especially mother, school environment). JFM is diagnosed on the combination of disease history, physical examination to determine the 18 tender points and allodynia, pain from gently touching their hair, and negative results of blood tests (inflammatory markers, thyroid function, myogenic enzymes). The goals of treatment are the following: restoration of function and relief of pain. Psychological support is advocated. Although the exact number of patients with JFM is still to be elucidated, it seems to be growing because pediatric rheumatologists in Japan encounter children with a wide variety of musculoskeletal pains. This guideline describes how to diagnose JFM in children and how to treat them appropriately.
© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.
戸田克広：線維筋痛症の分かる本．主婦の友社、2010.
西岡久寿樹：線維筋痛症対策の現状と展望．Pharma Medica 2006；24：9-13.
Burckhardt CS, Clark SR, Bennett RM.
The fibromyalgia impact questionnaire: development and validation.
J Rheumatol. 1991 May;18(5):728-33.
Abstract/Text
An instrument has been developed to assess the current health status of women with the fibromyalgia syndrome. The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item, self-administered instrument that measures physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being. We describe its development and validation. This initial assessment indicates that the FIQ has sufficient evidence of reliability and validity to warrant further testing in both research and clinical situations.
Osada K, Oka H, Isomura T, Nakamura I, Tominaga K, Takahashi S, Kojima A, Nishioka K.
Development of the Japanese version of the Fibromyalgia Impact Questionnaire (JFIQ): psychometric assessments of reliability and validity.
Int J Rheum Dis. 2011 Feb;14(1):74-80. doi: 10.1111/j.1756-185X.2010.01585.x.
Abstract/Text
AIM: To perform a psychometric assessment of the Japanese version of the Fibromyalgia Impact Questionnaire (JFIQ).
METHODS: Data for the psychometric assessment were collected from Japanese fibromyalgia (FM) patients who visited a clinic. Analyses were performed to examine the reliability and validity of the JFIQ.
RESULTS: A total of 56 patients were included in the analysis. There was no remarkable floor or ceiling effect for the JFIQ item or total scores. In the analysis of reproducibility, the interclass correlation coefficients of each item score and total score ranged from 0.61 to 0.95. Cronbach's alpha coefficient was 0.92. For the concurrent validity, the total score and most of the item scores correlated to every domain of Short Form-36 or Beck Depression Inventory-II to a moderate or great extent. The results of the known-group comparisons indicated that the total score tended to increase with the increase in severity of FM and pain (P-values for trend < 0.05).
CONCLUSION: This psychometric assessment demonstrated good reliability and validity of the JFIQ for use with Japanese FM patients. In the future, we expect that this questionnaire will be used in clinical studies and medical practice, and will be beneficial in the development of new therapies as well as for the comprehensive evaluation of patients' conditions in Japan.
© 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.
日本線維筋痛症学会・日本医療研究開発機構線維筋痛症研究班編、線維筋痛症診療ガイドライン2017、第3部資料、日本医事新報社、東京、p206.2017.
Wolfe F, Hassett AL, Walitt B, Michaud K.
Mortality in fibromyalgia: a study of 8,186 patients over thirty-five years.
Arthritis Care Res (Hoboken). 2011 Jan;63(1):94-101. doi: 10.1002/acr.20301. Epub 2010 Jul 26.
Abstract/Text
OBJECTIVE: To determine if mortality is increased among patients diagnosed as having fibromyalgia.
METHODS: We studied 8,186 fibromyalgia patients seen between 1974 and 2009 in 3 settings: all fibromyalgia patients in a clinical practice, patients participating in the US National Data Bank for Rheumatic Diseases (NDB), and patients invited to participate in the NDB who refused participation. Internal controls included 10,087 patients with osteoarthritis. Deaths were determined by multiple source communication, and all patients were also screened in the US National Death Index (NDI). We calculated standardized mortality ratios (SMRs) based on age- and sex-stratified US population data, after adjustment for NDI nonresponse.
RESULTS: There were 539 deaths, and the overall SMR was 0.90 (95% confidence interval [95% CI] 0.61-1.26). Among 1,665 clinic patients, the SMR was 0.92 (95% CI 0.81-1.05). Sensitivity analyses varying the rate of NDI nonidentification did not alter the nonassociation. Adjusted for age and sex, the hazard ratio for fibromyalgia compared with osteoarthritis was 1.05 (95% CI 0.94-1.17). The standardized mortality odds ratio (OR) compared with the US general population was increased for suicide (OR 3.31, 95% CI 2.15-5.11) and for accidental deaths (OR 1.45, 95% CI 1.02- 2.06), but not for malignancy.
CONCLUSION: Mortality does not appear to be increased in patients diagnosed with fibromyalgia, but the risk of death from suicide and accidents was increased.
Copyright © 2011 by the American College of Rheumatology.
Walitt B, Fitzcharles MA, Hassett AL, Katz RS, Häuser W, Wolfe F.
The longitudinal outcome of fibromyalgia: a study of 1555 patients.
J Rheumatol. 2011 Oct;38(10):2238-46. doi: 10.3899/jrheum.110026. Epub 2011 Jul 15.
Abstract/Text
OBJECTIVE: To describe the diagnosis status and outcome of patients diagnosed with fibromyalgia (FM) by US rheumatologists.
METHODS: We assessed 1555 patients with FM with detailed outcome questionnaires during 11,006 semiannual observations for up to 11 years. At entry, all patients satisfied American College of Rheumatology preliminary 2010 FM criteria modified for survey research. We determined diagnosis status, rates of improvement, responder subgroups, and standardized mean differences (effect sizes) between start and study completion scores of global well-being, pain, sleep problems, and health related quality of life. (QOL) RESULTS: The 5-year improvement rates were pain 0.4 (95% CI 0.2, 0.5), fatigue 0.4 (95% CI 0.2, 0.05), and global 0.0 (95% CI -0.1, 0.1). The standardized mean differences were patient global 0.03 (95% CI -0.02, 0.08), pain 0.22 (95% CI 0.16, 0.28), sleep problems 0.20 (95% CI 0.14, 0.25), physical component summary of the Short-form 36 (SF-36) 0.11 (95% CI -0.14, -0.07), and SF-36 mental component summary 0.03 (95% CI -0.07, 0.02). Patients switched between criteria-positive and criteria-negative states, with 716 patients (44.0%) failing to meet criteria at least once during 4228.5 patient-years (7448 observations). About 10% of patients had substantial improvement and about 15% had moderate improvement of pain. Overall, FM severity worsened in 35.9% and pain in 38.6%.
CONCLUSION: Although we found no average clinically meaningful improvement in symptom severity overall, 25% had at least moderate improvement of pain over time. The result that emerged from this longitudinal study was one of generally continuing high levels of self-reported symptoms and distress for most patients, but a slight trend toward improvement.
Deer TR, Sayed D, Pope JE, Chakravarthy KV, Petersen E, Moeschler SM, Abd-Elsayed A, Amirdelfan K, Mekhail N; ASPN COVID Workgroup.
Emergence From the COVID-19 Pandemic and the Care of Chronic Pain: Guidance for the Interventionalist.
Anesth Analg. 2020 Aug;131(2):387-394. doi: 10.1213/ANE.0000000000005000.
Abstract/Text
BACKGROUND: The current coronavirus disease 2019 (COVID-19) pandemic led to a significant disruption in the care of pain from chronic and subacute conditions. The impact of this cessation of pain treatment may have unintended consequences of increased pain, reduced function, increased reliance on opioid medications, and potential increased morbidity, due to the systemic impact of untreated disease burden. This may include decreased mobility, reduction in overall health status, and increase of opioid use with the associated risks.
METHODS: The article is the study of the American Society of Pain and Neuroscience (ASPN) COVID-19 task force to evaluate the policies set forth by federal, state, and local agencies to reduce or eliminate elective procedures for those patients with pain from spine, nerve, and joint disease. The impact of these decisions, which were needed to reduce the spread of the pandemic, led to a delay in care for many patients. We hence review an emergence plan to reinitiate this pain-related care. The goal is to outline a path to work with federal, state, and local authorities to combat the spread of the pandemic and minimize the deleterious impact of pain and suffering on our chronic pain patients.
RESULTS: The article sets forth a strategy for the interventional pain centers to reemerge from the current pandemic and to set a course for future events.
CONCLUSIONS: The COVID-19 pandemic represents an overwhelming challenge to interventional pain physicians and their patients. In addition to urgent actions needed for disease mitigation, the ASPN recommends a staged return to pain management professionals' workflow.
Clauw DJ, Häuser W, Cohen SP, Fitzcharles MA.
Considering the potential for an increase in chronic pain after the COVID-19 pandemic.
Pain. 2020 Aug;161(8):1694-1697. doi: 10.1097/j.pain.0000000000001950.
Abstract/Text
Ursini F, Ciaffi J, Mancarella L, Lisi L, Brusi V, Cavallari C, D'Onghia M, Mari A, Borlandelli E, Faranda Cordella J, La Regina M, Viola P, Ruscitti P, Miceli M, De Giorgio R, Baldini N, Borghi C, Gasbarrini A, Iagnocco A, Giacomelli R, Faldini C, Landini MP, Meliconi R.
Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey.
RMD Open. 2021 Aug;7(3). doi: 10.1136/rmdopen-2021-001735.
Abstract/Text
OBJECTIVE: Postacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19.
METHODS: Data were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual's attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey.
RESULTS: A final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, p<0.0001) and obesity (OR: 41.20, 95% CI 18.00 to 98.88, p<0.0001) were the strongest predictors of being classified as having post-COVID-19 FM. Hospital admission rate was significantly higher in men (15.8% vs 9.2%, p=0.001) and obese (19.2 vs 10.8%, p=0.016) respondents.
CONCLUSION: Our data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Clauw DJ, Calabrese L.
Rheumatology and Long COVID: lessons from the study of fibromyalgia.
Ann Rheum Dis. 2024 Jan 11;83(2):136-138. doi: 10.1136/ard-2023-224250. Epub 2024 Jan 11.
Abstract/Text
Rheumatology, such as other subspecialties, has both a unique perspective to offer as well as an evolving role to play in the global COVID-19 pandemic. Our field has already contributed meaningfully to the development and repurposing of many of the immune-based therapeutics which are now standard treatments for severe forms of the disease as well as to the understanding of the epidemiology, risk factors and natural history of COVID-19 in immune-mediated inflammatory diseases. Still in evolution is our potential to contribute to burgeoning research efforts in the next phase of the pandemic: the syndrome of postacute sequelae of COVID-19 or Long COVID. While our field brings many assets to the study of Long COVID including our expertise in the investigation of chronic inflammation and autoimmunity, our Viewpoint focuses on the strong similarities between fibromyalgia (FM) and Long COVID. While one can speculate on how embracing and confident practising rheumatologists already are regarding these interrelationships, we assert that in the emerging field of Long COVID the potential lessons from the field of fibromyalgia care and research have been underappreciated and marginalised and most importantly now deserve a critical appraisal.
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Rivera J, Castrejón I, Vallejo-Slocker L, Offenbächer M, Molina-Collada J, Trives L, López K, Caballero L, Hirsch JK, Toussaint L, Nieto JC, Alvaro-Gracia JM, Vallejo MA.
Clinical impact of confinement due to the COVID-19 pandemic on patients with fibromyalgia: a cohort study.
Clin Exp Rheumatol. 2021 May-Jun;39 Suppl 130(3):78-81. doi: 10.55563/clinexprheumatol/7lbz8n. Epub 2021 Mar 16.
Abstract/Text
OBJECTIVES: To our knowledge, the impact of the COVID-19 pandemic on fibromyalgia (FM) patients has not been studied before. FM patients often experience clinical impairment with stress. The aim of this study was to determine whether severity of FM increases because of confinement by the COVID-19 pandemic.
METHODS: This prospective study includes patients from the Combined Index of Severity of Fibromyalgia (ICAF) cohort who met the 2010 ACR FM criteria. In this cohort, all patients have a periodical evaluation of their quality of life through two questionnaires, the ICAF, which assesses the ability to perform daily living activities, anxiety and depression, and through the Patient Global Impression of Change (PGIC), which assesses overall change after a therapeutical intervention. Pre- and post-confinement measurements were analysed. Inferential statistical analysis and ANOVA for repeated measurements were used.
RESULTS: A total of 93 patients received a phone consultation, (95.5% females), mean (SD) age of 48.23 (8.38) years. Four patients were excluded as presenting COVID-19 and 51 (57%) completed the post-confinement ICAF. Following confinement, 25 (49%) patients got worse (group-worse) and 26 (51%) patients experienced no change or improved (group-stable). Comparisons between pre- and post-confinement ICAF did not show significant differences in both groups. Passive coping was significantly different in group-worse in pre-confinement evaluation. In the 80% of patients with passive coping predominance there were no changes in coping strategy.
CONCLUSIONS: No clinical impairment due to COVID-19 confinement occurred. The perceived worsening among FM patients relies primarily on how patients cope with their disease, without a real impact on clinical manifestations.
Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Kanazawa T, Itoh K, Yamano Y, Nakamura H, Nakajima T, Nishioka K.
The Japanese version of the modified ACR preliminary diagnostic criteria for fibromyalgia and the fibromyalgia symptom scale: reliability and validity.
Mod Rheumatol. 2013 Sep;23(5):846-50. doi: 10.1007/s10165-012-0759-x. Epub 2012 Sep 24.
Abstract/Text
PURPOSE: The aim of this study is to investigate the reliability and validity of the Japanese version of the modified American College of Rheumatology (ACR) Preliminary Diagnostic Criteria for Fibromyalgia (mACR 2010-J) and the Fibromyalgia Symptom Scale (mFS-J).
METHODS: According to the ACR 1990 classification criteria, patients with chronic pain were divided into the fibromyalgia group and nonfibromyalgia group (rheumatoid arthritis and osteoarthritis). Patients in both groups were assessed using mACR 2010-J and mFS-J.
RESULTS: 294 of 462 (64 %) patients in the fibromyalgia group met mACR 2010-J, whereas 4 % (9/231) of the nonfibromyalgia group did, with sensitivity of 64 %, specificity of 96 %, positive predictive value of 97 %, negative predictive value of 56 %, and positive likelihood ratio of 16.3. Mean total scores on mFS-J significantly differentiated the fibromyalgia from the nonfibromyalgia group. According to the value of the Youden index, the best cutoff score for the mFS-J was 9/10.
CONCLUSION: Our findings indicate that mACR 2010-J as a positive test and mFS-J as a quantification scale might be suitable for assessing fibromyalgia among Japanese chronic pain populations.
Salaffi F, Giorgi V, Sirotti S, Bongiovanni S, Farah S, Bazzichi L, Marotto D, Atzeni F, Rizzi M, Batticciotto A, Lombardi G, Galli M, Sarzi-Puttini P.
The effect of novel coronavirus disease-2019 (COVID-19) on fibromyalgia syndrome.
Clin Exp Rheumatol. 2021 May-Jun;39 Suppl 130(3):72-77. doi: 10.55563/clinexprheumatol/dnxtch. Epub 2020 Nov 16.
Abstract/Text
OBJECTIVES: Fibromyalgia syndrome (FM) is a complex disease that is mainly characterised by chronic widespread pain, fatigue and sleep disturbances and may be precipitated or worsened by many stressors. The aim of this study was to observe the behaviour of FM symptoms during the course of coronavirus disease 2019 (COVID-19).
METHODS: Patients who had been diagnosed as having FM for ≥3 months were recruited between February and May 2020. The collected data were age, sex, educational level and marital status; height and weight; and the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status 2019 (FASmod), and the Polysymptomatic Distress Scale (PDS). The patients were divided into those with or without concomitant COVID-19 infection.
RESULTS: Eight hundred and ninety-seven (93%) of the 965 patients (881 women [91.3%] and 84 men [8.7%]) were followed up on an outpatient basis because of FM and 68 (7.0%) were either followed up as out-patients or hospitalised because of COVID-19. There was no difference in the sociodemographic data of the two groups, but there were statistically significant between-group differences in the results of the clinimetric tests. The major differences between the score of the items (those with the greatest disease impact) were the following related symptoms: sleep quality (FIQR15), fatigue/energy (FIQR13), pain (FIQR12), stiffness (FIQR14).
CONCLUSIONS: The mean total and subdomain scores of all the tests were significantly higher in the patients with COVID-19, which suggests that global FM symptoms are more severe in patients with infection. Further studies of the post-COVID19 patients are being carried out in order to discover whether the worsened symptomatology continues because of their hypersensitised state.
Hruschak V, Flowers KM, Azizoddin DR, Jamison RN, Edwards RR, Schreiber KL.
Cross-sectional study of psychosocial and pain-related variables among patients with chronic pain during a time of social distancing imposed by the coronavirus disease 2019 pandemic.
Pain. 2021 Feb 1;162(2):619-629. doi: 10.1097/j.pain.0000000000002128.
Abstract/Text
The COVID-19 pandemic has had a tremendous impact, including on individuals with chronic pain. The social distancing policies necessary to slow the spread of SARS-CoV-2 have involved increased levels of social isolation. This cross-sectional survey study examined pain severity and interference among individuals with chronic pain during an early phase of social distancing mandates and identified characteristics of individuals who were most impacted. Approximately 4 to 8 weeks after social distancing mandates commenced in the state of Massachusetts, 150 patients with fibromyalgia, chronic spine, and postsurgical pain completed demographic, pain, social distancing, and validated psychosocial questionnaires. Patients self-reported an overall significant increase in pain severity and pain interference, compared with before social distancing, although both pain severity and interference were quite variable among individuals under conditions of social distancing. Several demographic, socioeconomic, and psychosocial factors were associated with greater pain severity and interference during social distancing. Multivariable linear regression demonstrated that female sex, nonwhite race, lower education, disability, fibromyalgia, and higher pain catastrophizing were independently associated with greater pain severity, while female sex and pain catastrophizing were independently associated greater pain interference. The findings suggest that individual differences among patients with chronic pain should be considered in the planning, development, and prioritization of interventions to improve pain care and to prevent worsening of symptoms during the continuing COVID-19 pandemic.
Copyright © 2020 International Association for the Study of Pain.
Aloush V, Gurfinkel A, Shachar N, Ablin JN, Elkana O.
Physical and mental impact of COVID-19 outbreak on fibromyalgia patients.
Clin Exp Rheumatol. 2021 May-Jun;39 Suppl 130(3):108-114. doi: 10.55563/clinexprheumatol/rxk6s4. Epub 2021 Mar 11.
Abstract/Text
OBJECTIVES: Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors.
METHODS: An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment.
RESULTS: Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p<0.01), lower levels of pain (p<0.05) and less sleep disturbances (p<0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p<0.01).
CONCLUSIONS: Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.
Eccleston C, Blyth FM, Dear BF, Fisher EA, Keefe FJ, Lynch ME, Palermo TM, Reid MC, Williams ACC.
Managing patients with chronic pain during the COVID-19 outbreak: considerations for the rapid introduction of remotely supported (eHealth) pain management services.
Pain. 2020 May;161(5):889-893. doi: 10.1097/j.pain.0000000000001885.
Abstract/Text
日本線維筋痛症学会・日本医療研究開発機構線維筋痛症研究班編：線維筋痛症診療ガイドライン2017．日本医事新報社、東京、2017.
Q線維筋痛症．厚労省慢性の痛み政策研究事業研究班監修、国内慢性疼痛関連10学会合同編集：慢性疼痛診療ガイドライン．真興交易（株）医書出版部、東京、2021、p263-276.
Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W.
Cannabis-based medicines for chronic neuropathic pain in adults.
Cochrane Database Syst Rev. 2018 Mar 7;3(3):CD012182. doi: 10.1002/14651858.CD012182.pub2. Epub 2018 Mar 7.
Abstract/Text
BACKGROUND: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain.
OBJECTIVES: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults.
SEARCH METHODS: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles.
SELECTION CRITERIA: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed.Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence).
AUTHORS' CONCLUSIONS: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.
Merante D.
The mirogabalin ALDAY phase 3 program in pain associated with fibromyalgia: the lessons learned.
Curr Med Res Opin. 2020 Apr;36(4):661-666. doi: 10.1080/03007995.2020.1725744. Epub 2020 Feb 23.
Abstract/Text
Aims: The main aim of this work was to identify and to share the lessons learned from the negative outcome of the mirogabalin ALDAY phase 3 clinical program in pain associated with fibromyalgia. These lessons are important to improve planning and design of future phase 3 programs in fibromyalgia.Methods: A systematic review from Cochrane Library, Medline, Embase, clinicaltrials.gov, pharmaceutical companies, and regulatory agencies' websites, was carried out starting from the development of gabapentin, the first α2δ ligand studied for the treatment of neuropathic pain and ending with the mirogabalin program.Results: Based on the outcome of the main fibromyalgia programs, several differences in design, primary endpoint choice, magnitude of placebo response, presence of an active comparator, and size of the entire clinical program were identified. This analysis focused on the negative primary results of the mirogabalin ALDAY program and found several contributing factors. Above all, the magnitude of placebo response and the unprecedented size of the program were identified. The number of study visits and procedures was also high and highly demanding on all subjects involved in ALDAY.Outcome: In terms of main lessons learned from ALDAY, the first was the need for a comprehensive patient-focused strategy to preliminarily identify the challenges of fibromyalgia based on patient perspective and study complexity. Second, there was a need for a harmonized, truly patient-centric, global regulatory guidance accepted by regulatory agencies. Third, ALDAY proved that a phase 2 proof of concept, dose ranging study is necessary before commencing any phase 3 program in fibromyalgia.
Bidari A, Moazen-Zadeh E, Ghavidel-Parsa B, Rahmani S, Hosseini S, Hassankhani A.
Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial.
Daru. 2019 Jun;27(1):149-158. doi: 10.1007/s40199-019-00257-4. Epub 2019 Mar 14.
Abstract/Text
BACKGROUND: Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM).
OBJECTIVES: To add to the very few lines of evidence that exist on the comparative safety and efficacy of these two medications.
METHODS: In this open-label randomized clinical trial, outpatient women, who were diagnosed with FM based on American College of Rheumatology 2010 criteria, and had an age range of 18-65 years old were assigned to either duloxetine 30-60 mg or pregabalin 75-150 mg per day for 4 weeks. Patients were excluded in cases of having used duloxetine, pregabalin, gabapentin, or antidepressants within 12 weeks prior to the study, having had a history of comorbid medical conditions that could provoke chronic pain, or having had comorbid neuropsychiatric disorders, except for major depressive/anxiety disorders. Primary outcomes were between-group differences in mean score changes from baseline to end point for Widespread Pain Index (WPI) and Beck Depression Inventory-II. Secondary outcomes were the same statistical estimates, but for Fibromyalgia Impact Questionnaire-Revised and 12-Item Short Form Survey. Descriptive statistics and independent samples t-test were the main methods of analysis. ( www.irct.ir ; IRCT2016030626935N1).
RESULTS: Among all the scales, only WPI scores improved with a statistically significant difference between the two treatment arms, favoring duloxetine (Mean difference in score change - 2.32, 95% CI, -4.46 to - 0.18; p = 0.034; Cohen's d 0.53 95% CI, 0.04 to 1.02). Drop out rate and cumulative incidence of nausea was significantly higher in the duloxetine arm compared to the pregabalin arm.
CONCLUSION: This study provides further evidence on higher efficacy of duloxetine compared to pregabalin for the treatment of pain in patients with fibromyalgia. Future comprehensive pragmatic clinical trials are warranted.
Alberti FF, Becker MW, Blatt CR, Ziegelmann PK, da Silva Dal Pizzol T, Pilger D.
Comparative efficacy of amitriptyline, duloxetine and pregabalin for treating fibromyalgia in adults: an overview with network meta-analysis.
Clin Rheumatol. 2022 Jul;41(7):1965-1978. doi: 10.1007/s10067-022-06129-8. Epub 2022 Mar 26.
Abstract/Text
Treatment recommendations for fibromyalgia (FM) include a range of predominantly pharmacological treatment options designed to ensure the maintenance of symptoms and improvement in the quality of life of these patients. Our aim is to identify and compare the efficacy of amitriptyline (AMT), duloxetine (DLX), and pregabalin (PGB) for reducing pain intensity by 30% (R30%) and 50% (R50%) in adult patients with fibromyalgia. The review was conducted in the Medline/PubMed, Cochrane Library, and Embase databases up to February 2022. This study included systematic reviews (SR) of randomized clinical trials (RCTs) targeting adult patients over 18 years of age diagnosed with fibromyalgia according to the criteria of scientific societies, which include the basic clinical diagnosis characterized by the presence of pressure sensitivity in at least 11 of the 18 tender points, in addition to the presence of widespread musculoskeletal pain for a period longer than 3 months and a general assessment of the patient's health status. Pregnant women and children or adolescents were excluded. The Rob 2.0 tool from the Cochrane Collaboration was used to assess the risk of bias in RCTs. The quality of evidence of the reviews included was assessed according to the Grading of Recommendations Assessment, Development and Evaluation-GRADE. A meta-analysis for the evidence network was performed using the Bayesian approach, which allows simultaneous comparison of all treatment options (medication and dose). The different treatments were ranked according to the response rate according to the surface under the curve (SUCRA), which was expressed as a percentage. The results were presented in tables and figures. The protocol with the detailed methods was registered in PROSPERO (CRD42021229264). Eight systematic reviews were identified, and, from these, 15 clinical trials comparing AMT (n = 273), DLX (n = 2595), and PGB (n = 3,506) against placebo were selected. For the outcome R30%, PGB 450 mg was superior to DLX 30 mg and PGB 150 mg, while DLX 20 mg and 30 mg were not superior to placebo. For the outcome R50%, AMT 25 mg was superior to all other alternatives evaluated. The calculation of the SUCRA indicated that PGB 450 mg was the best performance option for R30% and AMT 25 mg for R50%. PGB 150 mg was the drug with the worst performance in the two outcomes evaluated. The drugs evaluated showed benefits for pain reduction in patients with fibromyalgia. In the absence of direct comparison studies, indirect comparison meta-analyses are an important resource for assisting in clinical decision-making. Our data only provide an indicator of the effectiveness of the three drugs evaluated, but as with other health conditions, tolerability and safety are important for the decision-making process and clinical management. In this regard, we encourage caution in interpreting our data.
© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).
Ferreira GE, Abdel-Shaheed C, Underwood M, Finnerup NB, Day RO, McLachlan A, Eldabe S, Zadro JR, Maher CG.
Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews.
BMJ. 2023 Feb 1;380:e072415. doi: 10.1136/bmj-2022-072415. Epub 2023 Feb 1.
Abstract/Text
OBJECTIVE: To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition.
DESIGN: Overview of systematic reviews.
DATA SOURCES: PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews comparing any antidepressant with placebo for any pain condition in adults.
DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework.
RESULTS: 26 reviews (156 unique trials and >25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference -5.3, 95% confidence interval -7.3 to -3.3), postoperative pain (-7.3, -12.9 to -1.7), neuropathic pain (-6.8, -8.7 to -4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons).
CONCLUSIONS: Evidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews-seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022311073.
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Farag HM, Yunusa I, Goswami H, Sultan I, Doucette JA, Eguale T.
Comparison of Amitriptyline and US Food and Drug Administration-Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis.
JAMA Netw Open. 2022 May 2;5(5):e2212939. doi: 10.1001/jamanetworkopen.2022.12939. Epub 2022 May 2.
Abstract/Text
IMPORTANCE: Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.
OBJECTIVE: To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.
DATA SOURCES: Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020.
STUDY SELECTION: Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs.
DATA EXTRACTION AND SYNTHESIS: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.
MAIN OUTCOMES AND MEASURES: Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated.
RESULTS: A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.
CONCLUSIONS AND RELEVANCE: These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.
Birkinshaw H, Friedrich CM, Cole P, Eccleston C, Serfaty M, Stewart G, White S, Moore RA, Phillippo D, Pincus T.
Antidepressants for pain management in adults with chronic pain: a network meta-analysis.
Cochrane Database Syst Rev. 2023 May 10;5(5):CD014682. doi: 10.1002/14651858.CD014682.pub2. Epub 2023 May 10.
Abstract/Text
BACKGROUND: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.
OBJECTIVES: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.
SELECTION CRITERIA: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.
MAIN RESULTS: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.
AUTHORS' CONCLUSIONS: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Calandre EP, Rico-Villademoros F, Rodríguez-López CM.
Monotherapy or combination therapy for fibromyalgia treatment?
Curr Rheumatol Rep. 2012 Dec;14(6):568-75. doi: 10.1007/s11926-012-0278-y.
Abstract/Text
Fibromyalgia is a chronic pain disease whose clinical symptomatology also includes different symptom domains: fatigue, sleep disturbances, morning stiffness, dyscognition, and psychological distress. These associated symptoms usually vary in frequency and intensity from patient to patient. Because the efficacy of monotherapy is limited, more severely affected patients frequently require drug combinations. There is, however, scarce scientific information concerning the benefits and risks of such combinations. To date, only ten studies investigating the efficacy and tolerability of two-drug combinations have been published; some of these studies are old and/or studied drugs that are now known to be of little or no interest in fibromyalgia management. Thus, when polytherapy is considered, therapeutic decisions must be based on data from monotherapy trials and a sound knowledge of the pharmacological profile of each drug. Well-designed clinical trials exploring specific drug combinations selected on the basis of potential additive or synergistic effects should be performed.
Mease PJ, Farmer MV, Palmer RH, Gendreau RM, Trugman JM, Wang Y.
Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label study evaluating the safety and efficacy of adding milnacipran in patients with incomplete response to pregabalin.
Ther Adv Musculoskelet Dis. 2013 Jun;5(3):113-26. doi: 10.1177/1759720X13483894.
Abstract/Text
OBJECTIVE: To evaluate the safety, tolerability, and efficacy of adding milnacipran to pregabalin in patients with fibromyalgia who have experienced an incomplete response to pregabalin.
METHODS: In this randomized, multicenter, open-label study, patients received pregabalin 300 or 450 mg/day during a 4- to 12-week run-in period. Patients with weekly recall visual analog scale (VAS) pain score of at least 40 and up to 90, Patient Global Impression of Severity score of at least 4, and Patient Global Impression of Change (PGIC) score of at least 3 were classified as incomplete responders and randomized to continue pregabalin alone (n = 180) or receive milnacipran 100 mg/day added to pregabalin (n = 184). The primary efficacy parameter was responder status based on PGIC score of up to 2. The secondary efficacy parameter was change from randomization in weekly recall VAS pain score. Safety parameters included adverse events (AEs), vital signs, and clinical laboratory tests.
RESULTS: The percentage of PGIC responders was significantly higher with milnacipran added to pregabalin (46.4%) than with pregabalin alone (20.8%; p < 0.001). Mean improvement from randomization in weekly recall VAS pain scores was greater in patients receiving milnacipran added to pregabalin (-20.77) than in patients receiving pregabalin alone (-6.43; p < 0.001). During the run-in period, the most common treatment-emergent AEs with pregabalin were dizziness (22.8%), somnolence (17.3%), and fatigue (9.1%). During the randomized period, the most common treatment-emergent AEs with milnacipran added to pregabalin were nausea (12.5%), fatigue (10.3%), and constipation (9.8%).
CONCLUSIONS: In this exploratory, open-label study, adding milnacipran to pregabalin improved global status, pain, and other symptoms in patients with fibromyalgia with an incomplete response to pregabalin treatment.
Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C.
A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia.
Arthritis Rheum. 1996 Nov;39(11):1852-9. doi: 10.1002/art.1780391111.
Abstract/Text
OBJECTIVE: To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM).
METHODS: Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales (VAS) for global well-being (1 completed by the physician and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening.
RESULTS: Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS for pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score.
CONCLUSION: Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone.
Tzellos TG, Toulis KA, Goulis DG, Papazisis G, Zampeli VA, Vakfari A, Kouvelas D.
Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis.
J Clin Pharm Ther. 2010 Dec;35(6):639-56. doi: 10.1111/j.1365-2710.2009.01144.x.
Abstract/Text
WHAT IS KNOWN AND OBJECTIVES: Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom-based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta-analysis of relevant randomized double-blind placebo-controlled (RCT) were performed.
DATA SOURCES, EXTRACTION AND ANALYSIS: A literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL and the reference lists of relevant studies. Responders to treatment (>30% reduction in mean pain score) and dropouts due to lack of efficacy were used as primary outcome measures. Dropout rates and incidence of common adverse outcomes were also investigated. Four RCTs, reporting data on 2040 patients, were reviewed and three of them using PG were included in the meta-analysis.
RESULTS: Pregabalin at a dose of 600, 450 and 300 mg per day is effective in FBM compared to placebo (NNT: 7, upper 95% CI: 12, 450 mg). A number of adverse events (AE), such as dizziness, somnolence, dry mouth, weight gain, peripheral oedema, is consistently associated with treatment at any dose and could lead one out of four patients to quit treatment (NNH: 6, lower 95% CI: 4, 600 mg). Indirect comparison meta-analysis suggests that PB at a dose of 450 mg per day could result in more responders than at 300 mg, but this result needs to be interpreted with caution as there were no significant differences between 600 and 300 mg or between 600 and 450 mg. Data on GP is limited.
WHAT IS NEW AND CONCLUSIONS: The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible. Further evidence is necessary for more conclusive inferences.
© 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.
Straube S, Derry S, Moore RA, McQuay HJ.
Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company clinical trial reports.
Rheumatology (Oxford). 2010 Apr;49(4):706-15. doi: 10.1093/rheumatology/kep432. Epub 2010 Jan 7.
Abstract/Text
OBJECTIVES: Meta-analysis of pregabalin trials in FM using company trial reports, which provide more detailed information about trials than published papers. FM is a common condition with a significant impact on quality of life.
METHODS: Reports of five high-quality randomized trials (3808 patients) of pregabalin in FM were obtained from Pfizer. Four trials (2754 patients) were of classical trial design and one was an enriched enrolment randomized withdrawal design. Outcomes for meta-analysis from the four trials with classical design were pooled in an intention-to-treat analysis.
RESULTS: Significant benefit of pregabalin over placebo was seen for a variety of outcomes including mean pain and sleep scores, the proportion of patients achieving at least 50% pain relief and most of the individual domains of short-form 36. Only a minority of patients achieve moderate or substantial pain relief. The proportions of patients with any adverse event, somnolence or dizziness were also significantly greater with pregabalin than with placebo. There was no difference with regard to serious adverse events. A dose-response relationship was apparent for at least 50% pain relief and for adverse event outcomes.
CONCLUSIONS: Pregabalin is effective in treating FM and is relatively safe. The size of therapeutic effect is similar to that with other recent interventions such as duloxetine and the combination of tramadol and paracetamol. Enriched enrolment randomized withdrawal design gives similar results to classical trial designs in FM.
Moore RA, Wiffen PJ, Derry S, McQuay HJ.
Gabapentin for chronic neuropathic pain and fibromyalgia in adults.
Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007938. doi: 10.1002/14651858.CD007938.pub2. Epub 2011 Mar 16.
Abstract/Text
BACKGROUND: This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning.
OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management.
SEARCH STRATEGY: We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011.
SELECTION CRITERIA: Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMMPACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model.
MAIN RESULTS: Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo.There were insufficient data for comparisons with other active treatments.
AUTHORS' CONCLUSIONS: Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis.
Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ.
Amitriptyline for neuropathic pain and fibromyalgia in adults.
Cochrane Database Syst Rev. 2012 Dec 12;12:CD008242. doi: 10.1002/14651858.CD008242.pub2. Epub 2012 Dec 12.
Abstract/Text
BACKGROUND: Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage) and fibromyalgia, and is recommended in many guidelines. These types of pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.
OBJECTIVES: To assess the analgesic efficacy of amitriptyline for chronic neuropathic pain and fibromyalgia.To assess the adverse events associated with the clinical use of amitriptyline for chronic neuropathic pain and fibromyalgia.
SEARCH METHODS: We searched CENTRAL, MEDLINE, and EMBASE to September 2012, together with reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own handsearched database for older studies.
SELECTION CRITERIA: We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain or fibromyalgia.
DATA COLLECTION AND ANALYSIS: We extracted efficacy and adverse event data, and two study authors examined issues of study quality independently. We performed analysis using two tiers of evidence. The first tier used data meeting current best standards, where studies reported the outcome of at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) or other imputation method for dropouts, reported an intention-to-treat (ITT) analysis, lasted 8 to 12 weeks or longer, had a parallel-group design, and where there were at least 200 participants in the comparison. The second tier used data that failed to meet this standard and were therefore subject to potential bias.
MAIN RESULTS: Twenty-one studies (1437 participants) were included; they individually involved between 15 and 235 participants, only four involved over 100 participants, and the median study size was 44 participants. The median duration was six weeks. Ten studies had a cross-over design. Doses of amitriptyline were generally between 25 mg and 125 mg, and dose escalation was common.There was no top-tier evidence for amitriptyline in treating neuropathic pain or fibromyalgia.Second-tier evidence indicated no evidence of effect in cancer-related neuropathic pain or HIV-related neuropathic pain, but some evidence of effect in painful diabetic neuropathy (PDN), mixed neuropathic pain, and fibromyalgia. Combining the classic neuropathic pain conditions of PDN, postherpetic neuralgia (PHN) and post-stroke pain with fibromyalgia for second-tier evidence, in eight studies and 687 participants, there was a statistically significant benefit (risk ratio (RR) 2.3, 95% confidence interval (CI) 1.8 to 3.1) with a number needed to treat (NNT) of 4.6 (3.6 to 6.6). The analysis showed that even using this potentially biased data, only about 38% of participants benefited with amitriptyline and 16% with placebo; most participants did not get adequate pain relief. Potential benefits of amitriptyline were supported by a lower rate of lack of efficacy withdrawals; 8/153 (5%) withdrew because of lack of efficacy with amitriptyline and 14/119 (12%) with placebo.More participants experienced at least one adverse event; 64% of participants taking amitriptyline and 40% taking placebo. The RR was 1.5 (95% CI 1.4 to 1.7) and the number needed to treat to harm was 4.1 (95% CI 3.2 to 5.7). Adverse event and all-cause withdrawals were not different.
AUTHORS' CONCLUSIONS: Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many patients with neuropathic pain or fibromyalgia. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain or fibromyalgia, but only a minority of patients will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.It is unlikely that any large randomised trials of amitriptyline will be conducted in specific neuropathic pain conditions or in fibromyalgia to prove efficacy.
Häuser W, Urrútia G, Tort S, Uçeyler N, Walitt B.
Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia syndrome.
Cochrane Database Syst Rev. 2013 Jan 31;(1):CD010292. doi: 10.1002/14651858.CD010292. Epub 2013 Jan 31.
Abstract/Text
BACKGROUND: Fibromyalgia syndrome (FMS) is a clinically well-defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. Patients often report high disability levels and poor quality of life (QOL). Drug therapy focuses on reducing key symptoms and improving quality of life.
OBJECTIVES: To assess the benefits and harms of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo for treating FMS symptoms in adults.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2012, Issue 9), MEDLINE (1966 to September 2012), EMBASE (1980 to September 2012), www.clinicalstudyresults.org (U.S.-marketed pharmaceuticals) (to September 2012) and www.clinicaltrials.gov (to September 2012) for published and ongoing trials and examined the reference lists of reviewed articles.
SELECTION CRITERIA: We selected randomized, controlled trials of any formulation of SNRIs against placebo for the treatment of FMS in adults.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data from the included studies, and assessed the risks of bias of the studies. Discrepancies were resolved by discussion.
MAIN RESULTS: Ten studies were included with a total of 6038 participants. Five studies investigated duloxetine against placebo, and five investigated milnacipran against placebo. A total of 3611 participants were included into duloxetine or milnacipran groups and 2427 participants into placebo groups. The studies had a low risk of bias in general. Duloxetine and milnacipran had a small incremental effect over placebo in reducing pain (standardized mean difference (SMD) -0.23; 95% confidence interval (CI) -0.29 to -0.18; 6.1% relative improvement). One-hundred and ninety-two participants per 1000 on placebo reported an at least 50% pain reduction compared to 280 per 1000 on SNRIs (Risk ratio (RR) 1.49, 95% CI 1.35 to 1.64; number needed to treat to benefit (NNTB) 11, 95% CI 9 to 15). Duloxetine and milnacipran did not reduce fatigue substantially (SMD -0.14; 95% CI -0.19 to -0.08; 2.5% relative improvement; NNTB 17, 95% CI 12 to 29), and did not improve QOL substantially (SMD -0.20; 95% CI -0.25 to -0.14; 4.6% relative improvement; NNTB 12, 95% CI 9 to 17) compared to placebo. There were no statistically significant differences between either duloxetine or milnacipran and placebo in reducing sleep problems (SMD -0.07; 95% CI -0.16 to 0.03; 2.5% relative improvement). One-hundred and seven participants per 1000 on placebo dropped out due to adverse events compared to 196 per 1000 on SNRIs. The dropout rate due to adverse events in the duloxetine and milnacipran groups was statistically significantly higher than in placebo groups (RR 1.83, 95% CI 1.53 to 2.18; number needed to treat to harm (NNTH) 11, 95% CI 9 to 13). There was no statistically significant difference in serious adverse events between either duloxetine or milnacipran and placebo (RR 0.78, 95% CI 0.55 to 1.12).
AUTHORS' CONCLUSIONS: The SNRIs duloxetine and milnacipran provided a small incremental benefit over placebo in reducing pain. The superiority of duloxetine and milnacipran over placebo in reducing fatigue and limitations of QOL was not substantial. Duloxetine and milnacipran were not superior to placebo in reducing sleep problems. The dropout rates due to adverse events were higher for duloxetine and milnacipran than for placebo. The most frequently reported symptoms leading to stopping medication were nausea, dry mouth, constipation, headache, somnolence/dizziness and insomnia. Rare complications of both drugs may include suicidality, liver damage, abnormal bleeding, elevated blood pressure and urinary hesitation.
Yeephu S, Suthisisang C, Suttiruksa S, Prateepavanich P, Limampai P, Russell IJ.
Efficacy and safety of mirtazapine in fibromyalgia syndrome patients: a randomized placebo-controlled pilot study.
Ann Pharmacother. 2013 Jul-Aug;47(7-8):921-32. doi: 10.1345/aph.1R725. Epub 2013 Jun 4.
Abstract/Text
BACKGROUND: Data from an open-label trial suggest that mirtazapine might prove useful in treatment of fibromyalgia syndrome (FMS).
OBJECTIVE: To obtain preliminary efficacy data of mirtazapine for estimation of sample size requirements for a Phase 2 clinical trial in FMS.
METHODS: This 13-week randomized controlled trial compared the effects of mirtazapine 15 mg/day, mirtazapine 30 mg/day, and placebo in 40 patients with FMS. The primary outcomes were change in Pain Visual Analog Scale (PVAS) and proportion of pain responders (≥30% PVAS reduction). Secondary outcomes included scores from the Jenkins Sleep Scale (JSS), Patient Global Impression of Change (PGIC), Fibromyalgia Impact Questionnaire (FIQ), Hamilton Depression Rating Scale (HAM-D), Patient Global Assessment, and self-reported adverse events.
RESULTS: Significant within-group PVAS reductions from baseline were observed in all 3 groups, with the greatest improvement in the mirtazapine 30-mg group (p < 0.005); between-group difference was not significant. The proportion of pain responders did not meet significance criteria (66.67% for mirtazapine 30 mg, 50% for mirtazapine 15 mg, 41.67% for placebo). Significant within-group improvement in JSS scores was seen for mirtazapine 30 mg (p < 0.01) and mirtazapine 15 mg (p < 0.05). Between-group comparison achieved significance for JSS item 3, waking several times per night (p < 0.05). On the PGIC, 72.73% felt better with both mirtazapine dosages compared with 50% for placebo. Within-group FIQ responses indicated improvement in only mirtazapine-treated groups, whereas within-group improvement for HAM-D and Patient Global Assessment was observed in all groups. Based on our findings, the sample size requirement (80% power, 5% type I error) should be 83 per group to detect PVAS change difference between mirtazapine 30 mg and placebo. Common mirtazapine-related adverse events were increased appetite and weight gain.
CONCLUSIONS: Patients with FMS taking mirtazapine exhibited within-group significant improvement in most of the measured outcomes. Between-group analysis was predictably compromised by the small sample size. Mirtazapine was well tolerated. Further study with a larger sample size is likely to be useful.
Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C.
The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis.
CNS Drugs. 2012 Apr 1;26(4):297-307. doi: 10.2165/11598970-000000000-00000.
Abstract/Text
BACKGROUND: The role of antidepressants in the management of fibromyalgia syndrome (FMS) still needs to be determined.
OBJECTIVE: The objective of this study was to provide a quantitative analysis (meta-analysis) of the efficacy and harms of antidepressants in the management of adult FMS patients.
DATA SOURCES: The data sources used were the databases MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (until December 30, 2010), the reference lists of included articles, and the websites of the US National Institutes of Health (NIH) and the Pharmaceutical Research and Manufacturers of America (PhRMA).
STUDY SELECTION: Studies with a randomized controlled trial (RCT) design comparing any types of antidepressants with pharmacological placebo or head-to-head comparisons of different types of antidepressants in FMS patients were included. RCTs in which antidepressants were combined with any other defined treatment or antidepressants were tested against anything but drug placebo were excluded. Patients diagnosed with FMS according to predefined criteria of any age were included. To be included, studies had to assess at least one key domain of FMS (pain, sleep, fatigue, health-related quality of life [HRQOL]) as outcomes of efficacy and report total treatment discontinuation rates and/or dropout rates due to adverse events as outcomes for harms.
DATA EXTRACTION: Data were extracted according to protocols of previous systematic reviews on antidepressants in FMS. Methodology quality was assessed by the van Tulder score.
DATA SYNTHESIS: Standardized mean differences (SMD) were calculated for continuous outcomes by means and standard deviations and relative risks (RR) for 30% pain reduction and total dropout rate for comparisons of antidepressants with placebo. Examination of the combined results was performed by a random effects model. We used Cohen's categories to evaluate the magnitude of the effect size, calculated by SMD. Heterogeneity was tested by the I2 statistic. Thirty-five studies were included in the meta-analysis. The SMDs of serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) on pain, sleep, fatigue, depression and HRQOL were significant. Based on Cohen's categories, the effect size on pain was small and the ones on sleep, fatigue, depression and HRQOL were not substantial. 1481/3528 (42.0%) patients with SNRIs and 737/2304 (32.0%) patients with placebo reported a 30% pain reduction (number needed to treat [NNT] 10.0; 95% CI 8.00, 13.4; I2 = 4%). The RR of dropouts due to adverse events was 1.83 (95% CI 1.53, 2.18; I2 = 33%). The SMDs of selective serotonin reuptake inhibitors (SSRIs) on pain, sleep, depression and HRQOL were significant. Based on Cohen's categories, the effect sizes on pain, depression and HRQOL were small and the one on sleep not substantial. 72/198 (36.4%) patients with SSRIs and 40/194 (20.6%) patients with placebo reported a 30% pain reduction (NNT 6.3; 95% CI 4.1, 14.1). The RR of dropouts due to adverse events was 1.60 (95% CI 0.84, 3.04; I2 = 0%). The SMDs of tricyclic antidepressants (TCAs) on pain, sleep, fatigue and HRQOL were significant. Based on Cohen's categories, the effect sizes on pain and sleep were moderate and the ones on fatigue and HRQOL were small. 140/290 (48.3%) patients with TCAs and 70/252 (27.8%) patients with placebo reported a 30% pain reduction (NNT 4.9; 95% CI 3.5, 8.0). The RR of dropouts due to adverse events was 0.84 (95% CI 0.46, 1.52; I2 = 0%).
CONCLUSIONS: The TCA amitriptyline and the SNRIs duloxetine and milnacipran are first-line options for the treatment of FMS patients. Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.
日本線維筋痛症学会・日本医療研究開発機構線維筋痛症研究班編、線維筋痛症診療ガイドライン2017、CQ 8-4わが国の線維筋痛症に対するデュロキセチンの有効性はどうか、CQ8-5そのほかの抗うつ薬は繊維筋痛症に有効か、日本医事新報社、東京、p127-131.2017.
Roskell NS, Beard SM, Zhao Y, Le TK.
A meta-analysis of pain response in the treatment of fibromyalgia.
Pain Pract. 2011 Nov-Dec;11(6):516-27. doi: 10.1111/j.1533-2500.2010.00441.x. Epub 2010 Dec 28.
Abstract/Text
OBJECTIVE: This meta-analysis compared efficacy (pain response) of drugs that are licensed or commonly used in the treatment of fibromyalgia. A meta-analysis of safety measured via discontinuation because of adverse events was also performed.
METHODS: We conducted a meta-analysis of 21 clinical trials to estimate treatment differences vs. placebo, separately, for duloxetine, fluoxetine, gabapentin, milnacipran, pramipexole, pregabalin, either of two tricyclic antidepressants, and tramadol plus paracetamol. Indirect treatment comparisons using mixed treatment comparisons methodology were conducted for all pairwise comparisons. Pain response was analyzed as improvement of at least 30%, and separately of 50%, from baseline.
RESULTS: When compared with placebo, statistically significant pain responses (improvement of 30% and 50%) were observed for patients treated with duloxetine, milnacipran 200 mg/day, pregabalin 300 or 450 mg/day, and tramadol plus paracetamol. Treatment with fluoxetine, gabapentin, or milnacipran 100 mg/day resulted in significant findings for the 30% improvement in pain response. The meta-analysis showed a statistically increased risk of discontinuation because of adverse events for milnacipran 100 and 200 mg/day (both P < 0.001), and pregabalin 300 and 450 mg/day (P = 0.009 and P < 0.001, respectively). All other treatments, except fluoxetine, showed numerically increased risk over placebo for discontinuation because of adverse events. In the indirect comparisons, no pairwise comparison of active treatments reached statistical significance for either pain response end point.
CONCLUSION: All eight active treatments displayed evidence suggesting improvement over placebo in the treatment of pain in patients suffering from fibromyalgia. Indirect comparison of active treatments found no strong differences.
© 2011 RTI Health Solutions. Pain Practice © 2011 World Institute of Pain.
Fitzcharles MA, Ste-Marie PA, Gamsa A, Ware MA, Shir Y.
Opioid use, misuse, and abuse in patients labeled as fibromyalgia.
Am J Med. 2011 Oct;124(10):955-60. doi: 10.1016/j.amjmed.2011.05.031.
Abstract/Text
BACKGROUND: As pain is the cardinal symptom of fibromyalgia, it is logical that treatments directed toward pain relief will be commonly used. Analgesic drug therapy remains the traditional treatment intervention for most chronic pain conditions, with a progressive increased use of opioids in the past 20 years. Concerns about efficacy, risk-benefit ratio, and possible long-term effects of chronic opioid therapy have been raised. There is limited information about opioid treatment in fibromyalgia, with all current guidelines discouraging opioid use.
METHODS: A chart review of all patients referred to a tertiary care pain center clinic with a referring diagnosis of fibromyalgia was conducted to evaluate use of opioid medications.
RESULTS: We have recorded opioid use by 32% of 457 patients referred to a multidisciplinary fibromyalgia clinic, with over two thirds using strong opioids. Opioid use was more commonly associated with lower education, unemployment, disability payments, current unstable psychiatric disorder, a history of substance abuse, and previous suicide attempts.
CONCLUSION: We have observed negative health and psychosocial status in patients using opioids and labeled as fibromyalgia. Prolonged use of opioids in fibromyalgia requires evaluation.
Copyright © 2011 Elsevier Inc. All rights reserved.
非がん性慢性「疼」痛に対するオピオイド鎮痛薬処方ガイドライン. 日本ペインクリニック学会、2012、真興交易医書出版部.
日本線維筋痛症学会・日本医療研究開発機構線維筋痛症研究班編、線維筋痛症診療ガイドライン2017、CQ 8-9繊維筋痛症に対して強オピオイド系薬剤（麻薬）の適応があるか、日本医事新報社、東京、p137-138.2017.
Goldenberg DL, Burckhardt C, Crofford L.
Management of fibromyalgia syndrome.
JAMA. 2004 Nov 17;292(19):2388-95. doi: 10.1001/jama.292.19.2388.
Abstract/Text
CONTEXT: The optimal management of fibromyalgia syndrome (FMS) is unclear and comprehensive evidence-based guidelines have not been reported.
OBJECTIVE: To provide up-to-date evidence-based guidelines for the optimal treatment of FMS. DATA SOURCES, SELECTION, AND EXTRACTION: A search of all human trials (randomized controlled trials and meta-analyses of randomized controlled trials) of FMS was made using Cochrane Collaboration Reviews (1993-2004), MEDLINE (1966-2004), CINAHL (1982-2004), EMBASE (1988-2004), PubMed (1966-2004), Healthstar (1975-2000), Current Contents (2000-2004), Web of Science (1980-2004), PsychInfo (1887-2004), and Science Citation Indexes (1996-2004). The literature review was performed by an interdisciplinary panel, composed of 13 experts in various pain management disciplines, selected by the American Pain Society (APS), and supplemented by selected literature reviews by APS staff members and the Utah Drug Information Service. A total of 505 articles were reviewed.
DATA SYNTHESIS: There are major limitations to the FMS literature, with many treatment trials compromised by short duration and lack of masking. There are no medical therapies that have been specifically approved by the US Food and Drug Administration for management of FMS. Nonetheless, current evidence suggests efficacy of low-dose tricyclic antidepressants, cardiovascular exercise, cognitive behavioral therapy, and patient education. A number of other commonly used FMS therapies, such as trigger point injections, have not been adequately evaluated.
CONCLUSIONS: Despite the chronicity and complexity of FMS, there are pharmacological and nonpharmacological interventions available that have clinical benefit. Based on current evidence, a stepwise program emphasizing education, certain medications, exercise, cognitive therapy, or all 4 should be recommended.
Luciano JV, Martínez N, Peñarrubia-María MT, Fernández-Vergel R, García-Campayo J, Verduras C, Blanco ME, Jiménez M, Ruiz JM, López del Hoyo Y, Serrano-Blanco A; FibroQoL Study Group.
Effectiveness of a psychoeducational treatment program implemented in general practice for fibromyalgia patients: a randomized controlled trial.
Clin J Pain. 2011 Jun;27(5):383-91. doi: 10.1097/AJP.0b013e31820b131c.
Abstract/Text
OBJECTIVES: A recent meta-analysis concluded that multicomponent treatments are effective for some fibromyalgia (FM) symptoms. The objective of this study was to examine whether a psychoeducational intervention implemented in primary care is more effective than usual care for improving the functional status of patients with FM.
METHODS: This study was based on a randomized controlled trial. The 484 patients with FM included in a database of the Viladecans Hospital (Barcelona, Spain) were eligible for screening. Finally, 108 patients were randomly assigned to the intervention and 108 patients were assigned to usual care. The intervention comprised nine 2-hour sessions (5 sessions of education and 4 sessions of autogenic relaxation). The patients were assessed before and after the intervention with a battery of instruments (measuring sociodemographic data, medical comorbidities, functional status, trait anxiety, and social desirability).
RESULTS: The posttreatment drop-out rate was 9.7% (intervention: 6.5%; control: 13%). The intention-to-treat analyses showed significant differences between the groups at posttreatment: the intervention group improved in physical impairment, days not feeling well, pain, general fatigue, morning fatigue, stiffness, anxiety, and depression (medium effect size in most cases). The patients who responded to the intervention reported less trait anxiety at baseline than nonresponders. The absolute risk reduction with the intervention was 36.1% (95% confidence interval: 23.3-48.8) and the number needed to treat was 3 (95% confidence interval: 2.0-4.3).
DISCUSSION: A 2-month psychoeducational intervention improves the functional status of FM patients to a greater extent than usual care, at least in the short-term. The social desirability bias did not explain the reported outcomes. Trait anxiety was associated with response to treatment.
Lera S, Gelman SM, López MJ, Abenoza M, Zorrilla JG, Castro-Fornieles J, Salamero M.
Multidisciplinary treatment of fibromyalgia: does cognitive behavior therapy increase the response to treatment?
J Psychosom Res. 2009 Nov;67(5):433-41. doi: 10.1016/j.jpsychores.2009.01.012. Epub 2009 Mar 6.
Abstract/Text
OBJECTIVE: Multidisciplinary treatments (MTs) are usually recommended for reducing fibromyalgia (FM) symptoms and include physical exercise, drug management, education, and cognitive behavior therapy (CBT). However, there is no evidence that CBT adds efficacy to the other therapeutic components. This randomized controlled trial analyzed the response of FM patients to two MTs, with and without CBT, according to the presence of concurrent symptoms.
METHODS: Eighty-three women with FM were randomly assigned to MT or combined MT and CBT. The MT included medical intervention, physical training, education, and discussion of the syndrome. The CBT focused on coping with stress, modifying lifestyles, and changing pain behaviors. Demographic and clinical data, information regarding tender points, and questionnaire responses about functional capability [Fibromyalgia Impact Questionnaire (FIQ)], health status [36-item Short Form Health Survey (SF-36)], and mental health [Symptom Checklist-90-Revised (SCL-90-R)] were obtained at the beginning, at the end of the 15-week treatment, and at 6-month follow-up. Subgroups are identified in relation to treatment response.
RESULTS: Sixty-six women (80%) completed treatment. Although the variance of the total sample had changed at posttreatment (F=2.67, P=.031), there was no significant effect for the TimexTreatment interaction (F=1.65, P=.16). Univariate tests detected a significant fall in the FIQ score. The subgroup of patients with fatigue showed a better response with MT+CBT than with MT. At 6-month follow-up, the statistical differences had been maintained. Intention-to-treat analysis ratified these results.
CONCLUSIONS: MT improves functional capability and reduces symptom impact. CBT increases mildly the effect of MT in patients with fatigue.
Rooks DS, Gautam S, Romeling M, Cross ML, Stratigakis D, Evans B, Goldenberg DL, Iversen MD, Katz JN.
Group exercise, education, and combination self-management in women with fibromyalgia: a randomized trial.
Arch Intern Med. 2007 Nov 12;167(20):2192-200. doi: 10.1001/archinte.167.20.2192.
Abstract/Text
BACKGROUND: Self-management has increasingly been recommended as part of standard care for fibromyalgia, a common, poorly understood condition with limited treatment options. Data that assess popular self-management recommendations are scarce. We evaluated and compared the effectiveness of 4 common self-management treatments on function, symptoms, and self-efficacy in women with fibromyalgia.
METHODS: A total of 207 women with confirmed fibromyalgia were recruited from September 16, 2002, through November 30, 2004, and randomly assigned to 16 weeks of (1) aerobic and flexibility exercise (AE); (2) strength training, aerobic, and flexibility exercise (ST); (3) the Fibromyalgia Self-Help Course (FSHC); or (4) a combination of ST and FSHC (ST-FSHC). The primary outcome was change in physical function from baseline to completion of the intervention. Secondary outcomes included social and emotional function, symptoms, and self-efficacy.
RESULTS: Improvements in the mean Fibromyalgia Impact Questionnaire score in the 4 groups were -12.7 for the ST-FSHC group, -8.2 for the AE group, -6.6 for the ST group, and -0.3 for the FSHC group. The ST-FSHC group demonstrated greater improvement than the FSHC group (mean difference, -12.4; 95% confidence interval [CI], -23.1 to -1.7). The ST-FSHC (mean difference, 13.6; 95% CI, 2.3 to 24.9) and AE (mean difference, 13.1; 95% CI, 1.6 to 25.6) groups had similar improvements in physical function scores on the 36-Item Short-Form Health Survey. Bodily pain scores on the 36-Item Short-Form Health Survey improved in the ST-FSHC (14.8), AE (13.2), and ST (5.7) groups. Social function, mental health, fatigue, depression, and self-efficacy also improved. The beneficial effect on physical function of exercise alone and in combination with education persisted at 6 months.
CONCLUSIONS: Progressive walking, simple strength training movements, and stretching activities improve functional status, key symptoms, and self-efficacy in women with fibromyalgia actively being treated with medication. The benefits of exercise are enhanced when combined with targeted self-management education. Our findings suggest that appropriate exercise and patient education be included in the treatment of fibromyalgia.
Hughes G, Martinez C, Myon E, Taïeb C, Wessely S.
The impact of a diagnosis of fibromyalgia on health care resource use by primary care patients in the UK: an observational study based on clinical practice.
Arthritis Rheum. 2006 Jan;54(1):177-83. doi: 10.1002/art.21545.
Abstract/Text
OBJECTIVE: To investigate the impact of a diagnosis of fibromyalgia (FM) in clinical practice on health care resource use in the UK.
METHODS: Rates of visits, prescriptions, referral, and diagnostic testing were estimated in patients who had been diagnosed as having FM between 1998 and March 2003 in UK primary care and compared with those in matched controls. Rates were calculated in 6-month intervals from 10 years before until 4 years after the FM diagnosis.
RESULTS: Patients (2260) were newly diagnosed as having FM; 81.3% were women. Their mean age was 49 years. FM patients had considerably higher rates of visits, prescriptions, and testing from at least 10 years prior to diagnosis compared with controls. By the time of diagnosis, FM patients had 25 visits and 11 prescriptions per year compared with 12 visits and 4.5 prescriptions per year in controls. Visit rates were highest for depression, followed by fatigue, chest pain, headache, and sleep disturbance. Following diagnosis, visits for most symptoms and health care use markers declined, but within 2-3 years, most visits rose to levels at or higher than those at diagnosis.
CONCLUSION: Primary care patients who had been diagnosed as having FM reported higher rates of illness and health care resource use for at least 10 years prior to their diagnosis, which suggests that illness behavior may play a role. Being diagnosed as having FM may help patients cope with some symptoms, but the diagnosis has a limited impact on health care resource use in the longer term, possibly because there is little effective treatment.
Annemans L, Wessely S, Spaepen E, Caekelbergh K, Caubère JP, Le Lay K, Taïeb C.
Health economic consequences related to the diagnosis of fibromyalgia syndrome.
Arthritis Rheum. 2008 Mar;58(3):895-902. doi: 10.1002/art.23265.
Abstract/Text
OBJECTIVE: To evaluate the use and costs of medical resources before and after a diagnosis of fibromyalgia syndrome (FMS) in a large primary care population in the UK.
METHODS: We applied an existing data set for medical resource use among patients with a coded diagnosis of FMS. The observed quantities of 157 types of medical resource use before and after the diagnosis of FMS were multiplied by unit costs in order to calculate the cost of care (general practitioner [GP] visits, drugs, referrals, and diagnostics) within the National Health Service, excluding hospital costs. Costs before diagnosis were used in a trend analysis to predict later costs, assuming the diagnosis had never been made, and these predicted costs were compared with the observed costs after diagnosis.
RESULTS: Following a diagnosis of FMS, a decrease in costs as compared with the predicted trend was observed. In the 4 years after diagnosis, the average difference between the predicted and observed cost was pound66.21 per 6 months per patient. This suggests that making the diagnosis leads to savings and a decrease in resource use. The main effect was observed for tests and imaging ( pound24.02 per 6 months), followed by pharmaceuticals ( pound22.27), referrals ( pound15.56), and GP visits ( pound4.36).
CONCLUSION: Failure to diagnose a true case of FMS has its own costs, largely in excess GP visits, investigations, and prescriptions.
Busch AJ, Schachter CL, Overend TJ, Peloso PM, Barber KA.
Exercise for fibromyalgia: a systematic review.
J Rheumatol. 2008 Jun;35(6):1130-44. Epub 2008 May 1.
Abstract/Text
OBJECTIVE: Fibromyalgia (FM) is a syndrome expressed by chronic widespread pain often associated with reduced physical function. Exercise is a common recommendation in management of FM. We evaluated the effects of exercise training on global well-being, selected signs and symptoms, and physical function in individuals with FM.
METHODS: We searched Medline, Embase, CINAHL, SportDiscus, PubMed, PEDro, and the Cochrane Central Register for Controlled Trials to July 2005 and included randomized trials evaluating cardiorespiratory endurance, muscle strength, and flexibility. Methodological quality was assessed using the van Tulder and Jadad instruments. Training protocols were evaluated using American College of Sports Medicine (ACSM) guidelines. Clinical heterogeneity limited metaanalysis to 6 aerobic and 2 strength studies.
RESULTS: There were 2276 subjects across the 34 studies; 1264 subjects were assigned to exercise interventions. Metaanalysis of 6 studies provided moderate-quality evidence that aerobic-only exercise training at ACSM-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) and tender points (SMD 0.23, 95% CI -0.18 to 0.65). Strength and flexibility remain underevaluated; however, strength training may have a positive effect on FM symptoms.
CONCLUSION: Aerobic-only training has beneficial effects on physical function and some FM symptoms. Strength-only training may improve FM symptoms, but requires further study. Large, high-quality studies of exercise-only interventions that provide detailed information on exercise prescription and adherence are needed.
Bircan C, Karasel SA, Akgün B, El O, Alper S.
Effects of muscle strengthening versus aerobic exercise program in fibromyalgia.
Rheumatol Int. 2008 Apr;28(6):527-32. doi: 10.1007/s00296-007-0484-5. Epub 2007 Nov 3.
Abstract/Text
The purpose of this study was to compare the effects of aerobic training with a muscle-strengthening program in patients with fibromyalgia. Thirty women with fibromyalgia were randomized to either an aerobic exercise (AE) program or a strengthening exercise (SE) program for 8 weeks. Outcome measures included the intensity of fibromyalgia-related symptoms, tender point count, fitness (6-min walk distance), hospital anxiety and depression (HAD) scale, and short-form health survey (SF-36). There were significant improvements in both groups regarding pain, sleep, fatigue, tender point count, and fitness after treatment. HAD-depression scores improved significantly in both groups while no significant change occurred in HAD-anxiety scores. Bodily pain subscale of SF-36 and physical component summary improved significantly in the AE group, whereas seven subscales of SF-36, physical component summary, and mental component summary improved significantly in the SE group. When the groups were compared after treatment, there were no significant differences in pain, sleep, fatigue, tender point count, fitness, HAD scores, and SF-36 scores. AE and SE are similarly effective at improving symptoms, tender point count, fitness, depression, and quality of life in fibromyalgia.
Brosseau L, Wells GA, Tugwell P, Egan M, Wilson KG, Dubouloz CJ, Casimiro L, Robinson VA, McGowan J, Busch A, Poitras S, Moldofsky H, Harth M, Finestone HM, Nielson W, Haines-Wangda A, Russell-Doreleyers M, Lambert K, Marshall AD, Veilleux L; Ottawa Panel Members.
Ottawa Panel evidence-based clinical practice guidelines for strengthening exercises in the management of fibromyalgia: part 2.
Phys Ther. 2008 Jul;88(7):873-86. doi: 10.2522/ptj.20070115. Epub 2008 May 22.
Abstract/Text
BACKGROUND AND PURPOSE: The objective of this study was to create guidelines for the use of strengthening exercises in the management of adult patients (>18 years of age) with fibromyalgia (FM), as defined by the 1990 American College of Rheumatology criteria.
METHODS: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D-). From the rigorous literature search, 5 randomized controlled trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found.
RESULTS: There were 5 positive recommendations: 2 grade A and 3 grade C+. All 5 were of clinical benefit.
DISCUSSION AND CONCLUSION: The Ottawa Panel recommends strengthening exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.
Gusi N, Tomas-Carus P.
Cost-utility of an 8-month aquatic training for women with fibromyalgia: a randomized controlled trial.
Arthritis Res Ther. 2008;10(1):R24. doi: 10.1186/ar2377. Epub 2008 Feb 22.
Abstract/Text
INTRODUCTION: Physical therapy in warm water has been effective and highly recommended for persons with fibromyalgia, but its efficiency remains largely unknown. Should patients or health care managers invest in this therapy? The aim of the current study was to assess the cost-utility of adding an aquatic exercise programme to the usual care of women with fibromyalgia.
METHODS: Costs to the health care system and to society were considered in this study that included 33 participants, randomly assigned to the experimental group (n = 17) or a control group (n = 16). The intervention in the experimental group consisted of a 1-h, supervised, water-based exercise sessions, three times per week for 8 months. The main outcome measures were the health care costs and the number of quality-adjusted life-years (QALYs) using the time trade-off elicitation technique from the EuroQol EQ-5D instrument. Sensitivity analyses were performed for variations in staff salary, number of women attending sessions and time spent going to the pool. The cost effectiveness acceptability curves were created using a non-parametric bootstrap technique.
RESULTS: The mean incremental treatment costs exceeded those for usual care per patient by euro 517 for health care costs and euro 1,032 for societal costs. The mean incremental QALY associated with the intervention was 0.131 (95% CI: 0.011 to 0.290). Each QALY gained in association with the exercise programme cost an additional euro 3,947/QALY (95% CI: 1,782 to 47,000) for a health care perspective and euro 7,878/QALY (3,559 to 93,818) from a societal perspective. The curves showed a 95% probability that the addition of the water-based programme is a cost-effective strategy if the ceiling of inversion is euro 14,200/QALY from a health care perspective and euro 28,300/QALY from a societal perspective.
CONCLUSION: The addition of an aquatic exercise programme to the usual care regime for fibromyalgia in women is cost effective in terms of both health care costs and societal costs. However, the characteristics of facilities (distance from the patients' homes and number of patients that can be accommodated per session) are major determinants to consider before investing in such a programme.
TRIAL REGISTRATION: Current controlled trials ISRCTN53367487.
Tomas-Carus P, Gusi N, Häkkinen A, Häkkinen K, Leal A, Ortega-Alonso A.
Eight months of physical training in warm water improves physical and mental health in women with fibromyalgia: a randomized controlled trial.
J Rehabil Med. 2008 Apr;40(4):248-52. doi: 10.2340/16501977-0168.
Abstract/Text
OBJECTIVE: To evaluate the feasibility of 8 months of supervised exercise therapy in warm water and its effects on the impact of fibromyalgia on physical and mental health and physical fitness in affected women.
METHODS: Thirty women with fibromyalgia were randomly assigned to an exercise therapy group (n = 15) or a control group (inactive) (n = 15). The impact of fibromyalgia on physical and mental health was assessed using the Fibromyalgia Impact Questionnaire and the anxiety state with State-Trait Anxiety Inventory. Physical fitness was measured using the following tests: Canadian Aerobic Fitness; hand-grip dynamometry; 10-metre walking; 10-step stair-climbing and blind 1-leg stance.
RESULTS: After 8 months of training, the exercise therapy group improved compared with the control group in terms of physical function (20%), pain (8%), stiffness (53%), anxiety (41%), depression (27%), Fibromyalgia Impact Questionnaire total scores (18%), State-Trait Anxiety Inventory score (22%), aerobic capacity (22%), balance (30%), functional capacity for walking (6%), stair-climbing with no extra weight (14%) and stair-climbing 10 kg-weighted (25%).
CONCLUSION: Eight months of supervised exercise in warm water was feasible and led to long-term improvements in physical and mental health in patients with fibromyalgia at a similar magnitude to those of shorter therapy programmes.
Busch AJ, Webber SC, Brachaniec M, Bidonde J, Bello-Haas VD, Danyliw AD, Overend TJ, Richards RS, Sawant A, Schachter CL.
Exercise therapy for fibromyalgia.
Curr Pain Headache Rep. 2011 Oct;15(5):358-67. doi: 10.1007/s11916-011-0214-2.
Abstract/Text
Fibromyalgia syndrome, a chronic condition typically characterized by widespread pain, nonrestorative sleep, fatigue, cognitive dysfunction, and other somatic symptoms, negatively impacts physical and emotional function and reduces quality of life. Exercise is commonly recommended in the management of people with fibromyalgia, and interest in examining exercise benefits for those with the syndrome has grown substantially over the past 25 years. Research supports aerobic and strength training to improve physical fitness and function, reduce fibromyalgia symptoms, and improve quality of life. However, other forms of exercise (e.g., tai chi, yoga, Nordic walking, vibration techniques) and lifestyle physical activity also have been investigated to determine their effects. This paper highlights findings from recent randomized controlled trials and reviews of exercise for people with fibromyalgia, and includes information regarding factors that influence response and adherence to exercise to assist clinicians with exercise and physical activity prescription decision-making to optimize health and well-being.
Kaleth AS, Slaven JE, Ang DC.
Does increasing steps per day predict improvement in physical function and pain interference in adults with fibromyalgia?
Arthritis Care Res (Hoboken). 2014 Dec;66(12):1887-94. doi: 10.1002/acr.22398.
Abstract/Text
OBJECTIVE: To examine the concurrent and predictive associations between the number of steps taken per day and clinical outcomes in patients with fibromyalgia (FM).
METHODS: A total of 199 adults with FM (mean age 46.1 years, 95% women) who were enrolled in a randomized clinical trial wore a hip-mounted accelerometer for 1 week and completed self-report measures of physical function (Fibromyalgia Impact Questionnaire-Physical Impairment [FIQ-PI], Short Form 36 [SF-36] health survey physical component score [PCS], pain intensity and interference (Brief Pain Inventory [BPI]), and depressive symptoms (Patient Health Questionnaire-8 [PHQ-8]) as part of their baseline and followup assessments. Associations of steps per day with self-report clinical measures were evaluated from baseline to week 12 using multivariate regression models adjusted for demographic and baseline covariates.
RESULTS: Study participants were primarily sedentary, averaging 4,019 ± 1,530 steps per day. Our findings demonstrate a linear relationship between the change in steps per day and improvement in health outcomes for FM. Incremental increases on the order of 1,000 steps per day were significantly associated with (and predictive of) improvements in FIQ-PI, SF-36 PCS, BPI pain interference, and PHQ-8 (all P < 0.05). Although higher step counts were associated with lower FIQ and BPI pain intensity scores, these were not statistically significant.
CONCLUSION: Step count is an easily obtained and understood objective measure of daily physical activity. An exercise prescription that includes recommendations to gradually accumulate at least 5,000 additional steps per day may result in clinically significant improvements in outcomes relevant to patients with FM. Future studies are needed to elucidate the dose-response relationship between steps per day and patient outcomes in FM.
Copyright © 2014 by the American College of Rheumatology.
Sañudo B, Galiano D, Carrasco L, de Hoyo M, McVeigh JG.
Effects of a prolonged exercise program on key health outcomes in women with fibromyalgia: a randomized controlled trial.
J Rehabil Med. 2011 May;43(6):521-6. doi: 10.2340/16501977-0814.
Abstract/Text
OBJECTIVE: To assess the impact of a long-term exercise programme vs usual care on perceived health status, functional capacity and depression in patients with fibromyalgia.
DESIGN: Randomized controlled trial.
SUBJECTS: Forty-two women with fibromyalgia were allocated randomly to 1 of 2 groups: an experimental group that carried out aerobic, strength and flexibility exercises for 24 weeks and a usual care control group.
METHODS: Health status and functional capacity were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form Health Survey 36. Depression was evaluated with the Beck Depression Inventory.
RESULTS: Significant improvements were observed in health status and functional capacity for the exercise group over the control group. The magnitude of the effect size of these improvements, expressed as Cohen's d, was medium. The effect size (95% confidence interval) for the Fibromyalgia Impact Questionnaire was 0.58 (-14.12, -2.35), for the Short Form Health Survey 36. global score 0.54 (1.28, 14.52), and in the mental health domain of the Short Form Health Survey 36. 0.51 (1.20, 16.26). There was a large effect size in vitality. All the aforementioned improvements can be considered as clinically important changes.
CONCLUSION: Results confirm that a long-term combination of aerobic exercise, strengthening and flexibility improves psychological health status and health-related quality of life in patients with fibromyalgia.
Sañudo B, Galiano D, Carrasco L, Blagojevic M, de Hoyo M, Saxton J.
Aerobic exercise versus combined exercise therapy in women with fibromyalgia syndrome: a randomized controlled trial.
Arch Phys Med Rehabil. 2010 Dec;91(12):1838-43. doi: 10.1016/j.apmr.2010.09.006.
Abstract/Text
OBJECTIVE: To investigate the effects of supervised aerobic exercise (AE) and a combined program of supervised aerobic, muscle strengthening, and flexibility exercises (combined exercise [CE]) on important health outcomes in women with fibromyalgia syndrome (FMS).
DESIGN: Randomized controlled trial.
SETTING: Community-based supervised intervention.
PARTICIPANTS: Women (N=64) with a diagnosis of FMS according to the American College of Rheumatology criteria.
INTERVENTION: Participants were randomly allocated to 1 of 3 groups: supervised AE, supervised CE, or usual-care control. Exercise sessions were performed twice weekly (45-60min/session) for 24 weeks.
MAIN OUTCOME MEASURES: The primary outcome measure was the Fibromyalgia Impact Questionnaire (FIQ). Exploratory outcome measures were the 36-Item Short-Form Health Survey, Beck Depression Inventory (BDI), aerobic capacity (6-minute walk test), hand-grip strength, and range of motion in the shoulders and hips.
RESULTS: Compliance with both interventions was excellent, with women in the exercise groups attending more than 85% of sessions. A 14% to 15% improvement from baseline in total FIQ score was observed in the exercise groups (P≤.02) and was accompanied by decreases in BDI scores of 8.5 (P<.001) and 6.4 (P<.001) points in the AE and CE groups, respectively. Relative to nonexercising controls, CE evoked improvements in the SF-36 Physical Functioning (P=.003) and Bodily Pain (P=.003) domains and was more effective than AE for evoking improvements in the Vitality (P=.002) and Mental Health (P=.04) domains. Greater improvements also were observed in shoulder/hip range of motion and handgrip strength in the CE group.
CONCLUSION: Given the equivalent time commitment required for AE and CE, our results suggest that women with FMS can gain additional health benefits by engaging in a similar volume of CE.
Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Sañudo B, Carrasco L, de Hoyo M, McVeigh JG.
Effects of exercise training and detraining in patients with fibromyalgia syndrome: a 3-yr longitudinal study.
Am J Phys Med Rehabil. 2012 Jul;91(7):561-9; quiz 570-3. doi: 10.1097/PHM.0b013e31824faa03.
Abstract/Text
OBJECTIVE: This study aimed to evaluate the immediate effects of a 6-mo combined exercise program on quality-of-life, physical function, depression, and aerobic capacity in women with fibromyalgia syndrome and to determine the impact of repeated delivery of the intervention.
DESIGN: Forty-one women with fibromyalgia were randomly assigned to a training group (EG; n = 21) and a control group (CG; n = 20). Quality-of-life and physical function were assessed using the 36-item Short-Form Health Survey (SF-36) and the Fibromyalgia Impact Questionnaire, and depression was measured using the Beck Depression Inventory. Physical fitness was measured using the 6-min Walk Test. Outcomes were assessed at baseline and after each 6-mo intervention, which was delivered over 30 mos (6 mos of training and 6 mos of detraining).
RESULTS: After a 6-mo combined exercise program, there was a significant improvement in the Fibromyalgia Impact Questionnaire (P < 0.0005) for the training group over the control group. Repeated-measures analysis of variance across all time points demonstrated significant main effects for time for the Fibromyalgia Impact Questionnaire, SF-36, Beck Depression Inventory and the 6-min Walk Test, but there were no between-group interaction effects. For the EG, there were significant within-group changes in the Fibromyalgia Impact Questionnaire, SF-36, and Beck Depression Inventory at the final time point; however, there were no within-group changes for the control group. Improvement achieved for the training group were maintained during the detraining period.
CONCLUSIONS: A long-term exercise program can produce immediate improvements in key health domains in women with fibromyalgia. The benefits achieved with regular training can be maintained for 30 mos. The lack of difference between groups over time may be caused by attrition and consequent lack of power at the final time point.
Hammond A, Freeman K.
Community patient education and exercise for people with fibromyalgia: a parallel group randomized controlled trial.
Clin Rehabil. 2006 Oct;20(10):835-46. doi: 10.1177/0269215506072173.
Abstract/Text
OBJECTIVE: To evaluate the effects of a community patient education -exercise programme, using a cognitive-behavioural approach, for people with fibromyalgia.
DESIGN: A randomized, parallel group trial with assessments at 0, 4 and 8 months.
SETTING: Community leisure centres.
SUBJECTS: People with fibromyalgia (n=183) attending a rheumatology outpatient department at a large district general hospital.
INTERVENTIONS: Participants were randomized to a patient education-exercise group (n=97) or relaxation (attention control) group (n=86).
MAIN MEASURES: The Fibromyalgia Impact Questionnaire (0-80; lower score means better health). Secondary outcomes included: the Arthritis Self-Efficacy Scale(pain and other symptoms subscales: 1 -10 scale; higher scores mean greater self-efficacy) and self-reported improvement.
RESULTS: Fifty participants withdrew or were unable to attend and 133 completed and returned baseline questionnaires: patient education group (n=71); relaxation group (n=62); 120/133 participants were women. Average age was 48.53 (SD 10.89) years. Follow-up ranged between 73 and 82% of questionnaires returned. At four months, there was a difference in average changes in total Fibromyalgia Impact Questionnaire scores between the two groups: patient education group--3.38 (SD 9.35); relaxation group 0.3 (SD 8.85); P=0.02. Arthritis Self-Efficacy Scale scores were significantly higher in the patient education group: pain 0.59 (SD 1.45)compared to the relaxation group's--0.12 (SD 1.22); P=0.003; other symptoms (patient education group 0.72 (SD 1.33); relaxation group 0.03 (SD 1.16); P=0.002). At eight months these differences were no longer apparent. Forty-seven per cent in the patient education group self-reported improvement compared with 13% in the relaxation group (chi2=13.65; P=0.0001).
CONCLUSION: Short-term improvements resulted from the education -exercise programme but were not sustained. Appropriate selection may improve efficacy.
Rucco V, Feruglio C, Genco F, Mosanghini R.
[Autogenic training versus Erickson's analogical technique in treatment of fibromyalgia syndrome].
Riv Eur Sci Med Farmacol. 1995 Jan-Feb;17(1):41-50.
Abstract/Text
The AA have conducted a controlled trial to determine the efficacy of two verbal techniques for muscular relaxation on 53 patients with fibromyalgia. The subjects were assigned at random to a autogenous training group (27 patients) or a analogic Erickson's techniques group (26 patients). The autogenous training showed the presence of various limits: (1) application limits (in which notable difficulties had to be faced to train the patients with fibromyalgia to practice the Autogenous training due to the revelation of "intrusive thoughts" or "abreactions", or because of the incapacity of the patients to practice the exercises at home without hearing the instructions of a therapist); (2) limits of efficacy (the state of optimum training needed many therapeutic sittings in order to be achieved and the improvements regarded nighttime sleep and morning rigidity, however, these improvements were less than those obtained with the analogic Erickson's techniques). The Erickson's techniques have showed, instead, many advantages: numerous patients continued the treatment until it was finished; only a small number of therapeutic sittings were necessary. There was an improvement of all the parameters examined, superior compared to the results obtained in the group of patients treated with autogenous training.
Castel A, Pérez M, Sala J, Padrol A, Rull M.
Effect of hypnotic suggestion on fibromyalgic pain: comparison between hypnosis and relaxation.
Eur J Pain. 2007 May;11(4):463-8. doi: 10.1016/j.ejpain.2006.06.006. Epub 2006 Aug 4.
Abstract/Text
The main aims of this experimental study are: (1) to compare the relative effects of analgesia suggestions and relaxation suggestions on clinical pain, and (2) to compare the relative effect of relaxation suggestions when they are presented as "hypnosis" and as "relaxation training". Forty-five patients with fibromyalgia were randomly assigned to one of the following experimental conditions: (a) hypnosis with relaxation suggestions; (b) hypnosis with analgesia suggestions; (c) relaxation. Before and after the experimental session, the pain intensity was measured using a visual analogue scale (VAS) and the sensory and affective dimensions were measured with the McGill Pain Questionnaire. The results showed: (1) that hypnosis followed by analgesia suggestions has a greater effect on the intensity of pain and on the sensory dimension of pain than hypnosis followed by relaxation suggestions; (2) that the effect of hypnosis followed by relaxation suggestions is not greater than relaxation. We discuss the implications of the study on our understanding of the importance of suggestions used in hypnosis and of the differences and similarities between hypnotic relaxation and relaxation training.
戸田克広：エビデンスに基づく薬物治療（海外の事例を含む）．日本線維筋痛症学会編．線維筋痛症診療ガイドライン2011．日本医事新報社．2011．93-105.
Ohta H, Oka H, Usui C, Ohkura M, Suzuki M, Nishioka K.
A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia.
Arthritis Res Ther. 2012 Oct 12;14(5):R217. doi: 10.1186/ar4056. Epub 2012 Oct 12.
Abstract/Text
INTRODUCTION: Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan.
METHODS: This randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life.
RESULTS: A total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalin significantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events.
CONCLUSIONS: This trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalin is an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT00830167.
McCarberg B, Barkin RL, Zaleon C.
The management of neuropathic pain with a focus upon older adults.
Am J Ther. 2012 May;19(3):211-27. doi: 10.1097/MJT.0b013e31822119b3.
Abstract/Text
By the year 2030, it is projected that the US population over the age of 65 years will be 70 million (one-fifth of the US population). Pain of various etiologies initiates about 50% of yearly physician visits and is the most frequent reason for health care consultation in the United States identified commonly by the older patient. The negative impact on the patient coupled with less than optimal treatments often presented to the patient elicit patient and prescriber frustration with inadequate outcomes. This article is focused at pharmacotherapeutic selections to be utilized in a polymodal fashion for the older adult presenting with neuropathic pain. The pharmacotherapies are to be titrated in a patient-specific patient centered-patient focused-personalized pharmacotherapeutic care. The classes of agents discussed include antidepressants, mood stabilizers/antiseizure agents, opioids, anesthetics, and miscellaneous agents.
所澤 徹：圧痛点を11ヵ所以上持つ患者に対するビタミンB12高用量葉酸補充療法の検討 外来患者165例に対する検討．日本線維筋痛症学会 第4回学術集会プログラム・抄録集 2011：68.
戸田克広：メコバラミン（メチコバール（R））と葉酸（フォリアミン（R））の併用は線維筋痛症に有効．日本線維筋痛症学会 第4回学術集会プログラム・抄録集．2012：90.
Viola-Saltzman M, Watson NF, Bogart A, Goldberg J, Buchwald D.
High prevalence of restless legs syndrome among patients with fibromyalgia: a controlled cross-sectional study.
J Clin Sleep Med. 2010 Oct 15;6(5):423-7.
Abstract/Text
STUDY OBJECTIVES: To investigate the prevalence of restless legs syndrome (RLS) in fibromyalgia (FM) and determine the presence and amount of sleep disruption in FM patients with RLS. RLS and FM have been associated in uncontrolled studies using a variety of RLS definitions. We explored this relationship using a cross-sectional study design.
METHODS: FM cases that met the American College of Rheumatology diagnostic criteria were recruited through an academic referral clinic and advertising. Pain- and fatigue-free controls were recruited from the Seattle metropolitan area. We enrolled 172 FM patients (mean age 50 years, 93% female) and 63 pain- and fatigue-free controls (mean age 41 years, 56% female). RLS was ascertained by a self-administered validated diagnostic interview.
RESULTS: The age- and gender-adjusted prevalence of RLS was higher in the FM group than the control group (33.0%; 95% CI: 25.9, 40.1 vs. 3.1%; 95% CI: 0.0, 7.4; p = 0.001). Likewise, the FM group was more likely to report RLS (OR = 11.7; 95% CI: 2.6, 53.0), even after adjusting for age and gender. The mean Pittsburgh Sleep Quality Index score was higher among FM patients with RLS than those without (11.8 vs. 9.9; p = 0.01) but subjective limb pain measures did not differ between these 2 groups.
CONCLUSIONS: There is a higher prevalence and odds of RLS in those with FM compared to controls. Clinicians should routinely query FM patients regarding RLS symptoms because treatment of RLS can potentially improve sleep and quality of life in these patients.
Bernardy K, Füber N, Köllner V, Häuser W.
Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome - a systematic review and metaanalysis of randomized controlled trials.
J Rheumatol. 2010 Oct;37(10):1991-2005. doi: 10.3899/jrheum.100104. Epub 2010 Aug 3.
Abstract/Text
OBJECTIVE: We performed the first systematic review with metaanalysis of the efficacy of cognitive-behavioral therapies (CBT) in fibromyalgia syndrome (FM).
METHODS: We screened Cochrane Library, Medline, PsychINFO, and Scopus (through June 2009) and the reference sections of original studies and systematic reviews for CBT in FM. Randomized controlled trials (RCT) comparing CBT to controls were analyzed. Primary outcomes were pain, sleep, fatigue, and health-related quality of life (HRQOL). Secondary outcomes were depressed mood, self-efficacy pain, and healthcare-seeking behavior. Effects were summarized using standardized mean differences (SMD).
RESULTS: A total of 14 out of 27 RCT with 910 subjects with a median treatment time of 27 hours (range 6-75) over a median of 9 weeks (range 5-15) were included. CBT reduced depressed mood (SMD -0.24, 95% CI -0.40, -0.08; p = 0.004) at posttreatment. Sensitivity analyses showed that the positive effect on depressed mood could not be distinguished from some risks of bias. There was no significant effect on pain, fatigue, sleep, and HRQOL at posttreatment and at followup. There was a significant effect on self-efficacy pain posttreatment (SMD 0.85, 95% CI 0.25, 1.46; p = 0.006) and at followup (SMD 0.90, 95% CI 0.14, 1.66; p = 0.02). Operant behavioral therapy significantly reduced the number of physician visits at followup (SMD -1.57, 95% CI -2.00, -1.14; p < 0.001).
CONCLUSION: CBT can be considered to improve coping with pain and to reduce depressed mood and healthcare-seeking behavior in FM.
Glombiewski JA, Sawyer AT, Gutermann J, Koenig K, Rief W, Hofmann SG.
Psychological treatments for fibromyalgia: a meta-analysis.
Pain. 2010 Nov;151(2):280-295. doi: 10.1016/j.pain.2010.06.011. Epub 2010 Aug 19.
Abstract/Text
The aims of the present analysis were to investigate the short- and long-term efficacies and treatment moderators of psychological interventions for fibromyalgia. A literature search using PubMed, PsychINFO, the Cochrane Library, and manual searches identified 23 eligible studies including 30 psychological treatment conditions and 1396 patients. Meta-analytic integration resulted in a significant but small effect size for short-term pain reduction (Hedges's g=0.37, 95% confidence interval (CI): 0.27-0.48) and a small-to-medium effect size for long-term pain reduction over an average follow-up phase of 7.4 months (Hedges's g=0.47, 95% CI: 0.3-0.65) for any psychological intervention. Psychological treatments also proved effective in reducing sleep problems (Hedges's g=0.46, 95% CI: 0.28-0.64), depression (Hedges's g=0.33, 95% CI: 0.20-0.45), functional status (Hedges's g=0.42, 95% CI: 0.25-0.58), and catastrophizing (Hedges's g=0.33, 95% CI: 0.17-0.49). These effects remained stable at follow-up. Moderator analyses revealed cognitive-behavioral treatment to be significantly better than other psychological treatments in short-term pain reduction (Hedges's g=0.60, 95% CI: 0.46-0.76). Higher treatment dose was associated with better outcome. Publication-bias analyses demonstrated that the effect sizes were robust. The results suggest that the effects of psychological treatments for fibromyalgia are relatively small but robust and comparable to those reported for other pain and drug treatments used for this disorder. Cognitive-behavioral therapy was associated with the greatest effect sizes.
Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Thieme K, Flor H, Turk DC.
Psychological pain treatment in fibromyalgia syndrome: efficacy of operant behavioural and cognitive behavioural treatments.
Arthritis Res Ther. 2006;8(4):R121. doi: 10.1186/ar2010.
Abstract/Text
The present study focused on the evaluation of the effects of operant behavioural (OBT) and cognitive behavioural (CBT) treatments for fibromyalgia syndrome (FMS). One hundred and twenty-five patients who fulfilled the American College of Rheumatology criteria for FMS were randomly assigned to OBT (n = 43), CBT (n = 42), or an attention-placebo (AP) treatment (n = 40) that consisted of discussions of FMS-related problems. Assessments of physical functioning, pain, affective distress, and cognitive and behavioural variables were performed pre-treatment and post-treatment as well as 6 and 12 months post-treatment. Patients receiving the OBT or CBT reported a significant reduction in pain intensity post-treatment (all Fs > 3.89, all Ps < 0.01). In addition, the CBT group reported statistically significant improvements in cognitive (all Fs > 7.95, all P < 0.01) and affective variables (all Fs > 2.99, all Ps < 0.02), and the OBT group demonstrated statistically significant improvements in physical functioning and behavioural variables (all Fs > 5.99, all Ps < 0.001) compared with AP. The AP group reported no significant improvement but actually deterioration in the outcome variables. The post-treatment effects for the OBT and CBT groups were maintained at both the 6- and 12-month follow-ups. These results suggest that both OBT and CBT are effective in treating patients with FMS with some differences in the outcome measures specifically targeted by the individual treatments compared with an unstructured discussion group. The AP group showed that unstructured discussion of FMS-related problems may be detrimental.
Usui C, Doi N, Nishioka M, Komatsu H, Yamamoto R, Ohkubo T, Ishizuka T, Shibata N, Hatta K, Miyazaki H, Nishioka K, Arai H.
Electroconvulsive therapy improves severe pain associated with fibromyalgia.
Pain. 2006 Apr;121(3):276-280. doi: 10.1016/j.pain.2005.12.025. Epub 2006 Feb 21.
Abstract/Text
The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper-responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck's depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.
Huuhka MJ, Haanpää ML, Leinonen EV.
Electroconvulsive therapy in patients with depression and fibromyalgia.
Eur J Pain. 2004 Aug;8(4):371-6. doi: 10.1016/j.ejpain.2003.11.001.
Abstract/Text
The effect of electroconvulsive therapy (ECT) on depression and other symptoms of fibromyalgia was studied in a prospective 3-month trial in 13 patients with fibromyalgia and concomitant depression. All the patients met the DSM-IV diagnostic criteria for Major Depressive Disorder and fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. The Montgomery and Asberg Depression Rating Scale (MADRS) and the clinical global impression scale (CGI) were used to assess the severity of depression and the clinical change of the patients. The fibromyalgia impact questionnaire (FIQ) was used to evaluate the severity of the fibromyalgia symptoms. The intensity of pain was evaluated using a 6-point scale (0=no pain, 5=very severe pain), and tender point palpation. All assessments were performed at baseline and at follow-up visits, which took place one week, one month and three months after ECT. There was a significant improvement in depression after ECT according to MADRS. Using CGI, six patients were much or very much improved, while four patients were minimally improved and three patients had no change. There was significant improvement in four out of ten FIQ item scores, "feel good", "fatigue", "anxiety" and "depression". No significant change was found in the FIQ item scores "physical function", "pain", "stiffness" and "morning tiredness" or number of tender points and self-reported pain. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on the pain or other physical symptoms of these patients.
Passard A, Attal N, Benadhira R, Brasseur L, Saba G, Sichere P, Perrot S, Januel D, Bouhassira D.
Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.
Brain. 2007 Oct;130(Pt 10):2661-70. doi: 10.1093/brain/awm189. Epub 2007 Sep 14.
Abstract/Text
Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self-reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia.
Short BE, Borckardt JJ, Anderson BS, Frohman H, Beam W, Reeves ST, George MS.
Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: a randomized, controlled pilot study.
Pain. 2011 Nov;152(11):2477-2484. doi: 10.1016/j.pain.2011.05.033. Epub 2011 Jul 20.
Abstract/Text
Transcranial magnetic stimulation (TMS) of the prefrontal cortex can cause changes in acute pain perception. Several weeks of daily left prefrontal TMS has been shown to treat depression. We recruited 20 patients with fibromyalgia, defined by American College of Rheumatology criteria, and randomized them to receive 4000 pulses at 10 Hz TMS (n=10), or sham TMS (n=10) treatment for 10 sessions over 2 weeks along with their standard medications, which were fixed and stable for at least 4 weeks before starting sessions. Subjects recorded daily pain, mood, and activity. Blinded raters assessed pain, mood, functional status, and tender points weekly with the Brief Pain Inventory, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire. No statistically significant differences between groups were observed. Patients who received active TMS had a mean 29% (statistically significant) reduction in pain symptoms in comparison to their baseline pain. Sham TMS participants had a 4% nonsignificant change in daily pain from their baseline pain. At 2 weeks after treatment, there was a significant improvement in depression symptoms in the active group compared to baseline. Pain reduction preceded antidepressant effects. TMS was well tolerated, with few side effects. Further studies that address study limitations are needed to determine whether daily prefrontal TMS may be an effective, durable, and clinically useful treatment for fibromyalgia symptoms.
Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Marlow NM, Bonilha HS, Short EB.
Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review.
Pain Pract. 2013 Feb;13(2):131-45. doi: 10.1111/j.1533-2500.2012.00562.x. Epub 2012 May 28.
Abstract/Text
OBJECTIVE: To systematically review the literature to date applying repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for patients with fibromyalgia syndrome (FMS).
METHOD: Electronic bibliography databases screened included PubMed, Ovid MEDLINE, PsychINFO, CINAHL, and Cochrane Library. The keyword "fibromyalgia" was combined with ("transcranial" and "stimulation") or "TMS" or "tDCS" or "transcranial magnetic stimulation" or "transcranial direct current stimulation".
RESULTS: Nine of 23 studies were included; brain stimulation sites comprised either the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC). Five studies used rTMS (high-frequency-M1: 2, low-frequency-DLPFC: 2, high-frequency-DLPFC: 1), while 4 applied tDCS (anodal-M1: 1, anodal-M1/DLPFC: 3). Eight were double-blinded, randomized controlled trials. Most (80%) rTMS studies that measured pain reported significant decreases, while all (100%) tDCS studies with pain measures reported significant decreases. Greater longevity of significant pain reductions was observed for excitatory M1 rTMS/tDCS.
CONCLUSION: Studies involving excitatory rTMS/tDCS at M1 showed analogous pain reductions as well as considerably fewer side effects compared to FDA apaproved FMS pharmaceuticals. The most commonly reported side effects were mild, including transient headaches and scalp discomforts at the stimulation site. Yearly use of rTMS/tDCS regimens appears costly ($11,740 to 14,507/year); however, analyses to apapropriately weigh these costs against clinical and quality of life benefits for patients with FMS are lacking. Consequently, rTMS/tDCS should be considered when treating patients with FMS, particularly those who are unable to find adequate symptom relief with other therapies. Further work into optimal stimulation parameters and standardized outcome measures is needed to clarify associated efficacy and effectiveness.
© 2012 The Authors. Pain Practice © 2012 World Institute of Pain.
Zhu PA, Xie JY, Liu H, Wen Y, Shao YJ, Bao X.
Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis.
Arch Phys Med Rehabil. 2023 Jan;104(1):151-159. doi: 10.1016/j.apmr.2022.05.006. Epub 2022 May 27.
Abstract/Text
OBJECTIVE: The purpose of this review was to systematically assess the effectiveness of 10-Hz repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia.
DATA SOURCES: We searched PubMed, Cochrane Library, Embase, Web of Science, and Ovid databases as of November 6, 2021.
STUDY SELECTION: The inclusion criteria for this review were randomized controlled trials of 10-Hz rTMS for fibromyalgia, exploring the effects of 10-Hz rTMS on pain, depression, and quality of life in patients with fibromyalgia.
DATA EXTRACTION: Data extraction was performed independently by 2 evaluators according to predefined criteria, and the quality of the included literature was assessed using the Cochrane Bias Risk Assessment Tool. The measurement outcomes include visual analog scale, Hamilton Depression Rating Scale, and Fibromyalgia Impact Questionnaire, and so on.
DATA SYNTHESIS: A total of 488 articles were screened, and the final 7 selected high-quality articles with 217 patients met our inclusion criteria. Analysis of the results showed that high-frequency transcranial magnetic stimulation at 10 Hz was significantly associated with reduced pain compared with sham stimulation in controls (standardized mean difference [SMD]=-0.72; 95% confidence interval [CI], -1.12 to -0.33; P<.001; I2=46%) and was able to improve quality of life (SMD=-0.70; 95% CI, -1.00 to -0.40; P<.001; I2=15%) but not improve depression (SMD=-0.23; 95% CI, -0.50 to 0.05; P=.11; I2=33%). In addition, a subgroup analysis of pain conducted based on stimulation at the primary motor cortex and dorsolateral prefrontal cortex showed no significant difference (SMD=-0.72; 95% CI, -1.12 to -0.33; P=.10; I2=62%).
CONCLUSIONS: Overall, 10-Hz rTMS has a significant effect on analgesia and improved quality of life in patients with FMS but did not improve depression.
Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, Boggio PS, Fregni F.
Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial.
J Pain Manag. 2009;2(3):353-361.
Abstract/Text
Fibromyalgia has been recognized as a central pain disorder with evidence of neuroanatomic and neurophysiologic alterations. Previous studies with techniques of noninvasive brain stimulation--transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)--have shown that these methods are associated with a significant alleviation of fibromyalgia-associated pain and sleep dysfunction. Here we sought to determine whether a longer treatment protocol involving 10 sessions of 2 mA, 20 min tDCS of the left primary motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer additional, more long-lasting clinical benefits in the management of pain from fibromyalgia. METHODS: Forty-one women with chronic, medically refractory fibromyalgia were randomized to receive 10 daily sessions of M1, DLPFC, or sham tDCS. RESULTS: Our results show that M1 and DLPFC stimulation both display improvements in pain scores (VAS) and quality of life (FIQ) at the end of the treatment protocol, but only M1 stimulation resulted in long-lasting clinical benefits as assessed at 30 and 60 days after the end of treatment. CONCLUSIONS: This study demonstrates the importance of the duration of the treatment period, suggesting that 10 daily sessions of tDCS result in more long lasting outcomes than only five sessions. Furthermore, this study supports the findings of a similarly designed rTMS trial as both induce pain reductions that are equally long-lasting.
Gikaro JM, Bigambo FM, Minde VM, Swai EA.
Efficacy of electrophysical agents in fibromyalgia: A systematic review and network meta-analysis.
Clin Rehabil. 2023 Oct;37(10):1295-1310. doi: 10.1177/02692155231170450. Epub 2023 Apr 20.
Abstract/Text
OBJECTIVE: To examine the effectiveness of electrophysical agents in fibromyalgia.
DATA SOURCES: CINAHL, Cochrane Library, Embase, Medline, PEDro, and Web of Science were searched from their inceptions to March 27, 2023.
METHODS: This study was registered in PROSPERO (CRD42022354326). Methodological quality of included trials was assessed using PEDro scale, and the quality of evidence was determined according to the Grading of Recommendations Assessment, Development, and Evaluation system. The primary outcomes were pain, functional status, and mood.
RESULTS: Fifty-four studies involving 3045 patients with fibromyalgia were eligible for qualitative synthesis and 47 (pain), 31 (functional status), and 26 (mood) for network meta-analysis. The network consistency model revealed that, when compared with true control, transcutaneous electrical nerve stimulation and microcurrent improved pain symptoms (P = 0.006 and P = 0.037, respectively); repetitive transcranial magnetic stimulation improved patient functional status (P = 0.018); and microcurrent (P = 0.001), repetitive transcranial magnetic stimulation (P = 0.022), and no treatment (P = 0.038) significantly improved mood after intervention. Surface under the cumulative ranking indicated that microcurrent was most likely to be the best for managing pain and mood (surface under the cumulative ranking: 70% and 100%, respectively); low-level laser therapy for pain and mood (80% and 70%, respectively); and repetitive transcranial magnetic stimulation for improving functional status and mood (80% and 70%, respectively).
CONCLUSION: This review found low to moderate quality evidence that microcurrent, laser therapy, and repetitive transcranial magnetic stimulation are the most effective electrophysical agents for improving at least one outcome in fibromyalgia.
Assefi NP, Sherman KJ, Jacobsen C, Goldberg J, Smith WR, Buchwald D.
A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia.
Ann Intern Med. 2005 Jul 5;143(1):10-9. doi: 10.7326/0003-4819-143-1-200507050-00005.
Abstract/Text
BACKGROUND: Fibromyalgia is a common chronic pain condition for which patients frequently use acupuncture.
OBJECTIVE: To determine whether acupuncture relieves pain in fibromyalgia.
DESIGN: Randomized, sham-controlled trial in which participants, data collection staff, and data analysts were blinded to treatment group.
SETTING: Private acupuncture offices in the greater Seattle, Washington, metropolitan area.
PATIENTS: 100 adults with fibromyalgia.
INTERVENTION: Twice-weekly treatment for 12 weeks with an acupuncture program that was specifically designed to treat fibromyalgia, or 1 of 3 sham acupuncture treatments: acupuncture for an unrelated condition, needle insertion at nonacupoint locations, or noninsertive simulated acupuncture.
MEASUREMENTS: The primary outcome was subjective pain as measured by a 10-cm visual analogue scale ranging from 0 (no pain) to 10 (worst pain ever). Measurements were obtained at baseline; 1, 4, 8, and 12 weeks of treatment; and 3 and 6 months after completion of treatment. Participant blinding and adverse effects were ascertained by self-report. The primary outcomes were evaluated by pooling the 3 sham-control groups and comparing them with the group that received acupuncture to treat fibromyalgia.
RESULTS: The mean subjective pain rating among patients who received acupuncture for fibromyalgia did not differ from that in the pooled sham acupuncture group (mean between-group difference, 0.5 cm [95% CI, -0.3 cm to 1.2 cm]). Participant blinding was adequate throughout the trial, and no serious adverse effects were noted.
LIMITATIONS: A prescription of acupuncture at fixed points may differ from acupuncture administered in clinical settings, in which therapy is individualized and often combined with herbal supplementation and other adjunctive measures. A usual-care comparison group was not studied.
CONCLUSION: Acupuncture was no better than sham acupuncture at relieving pain in fibromyalgia.
Harris RE, Tian X, Williams DA, Tian TX, Cupps TR, Petzke F, Groner KH, Biswas P, Gracely RH, Clauw DJ.
Treatment of fibromyalgia with formula acupuncture: investigation of needle placement, needle stimulation, and treatment frequency.
J Altern Complement Med. 2005 Aug;11(4):663-71. doi: 10.1089/acm.2005.11.663.
Abstract/Text
OBJECTIVES: The objective of this study was to investigate whether typical acupuncture methods such as needle placement, needle stimulation, and treatment frequency were important factors in fibromyalgia symptom improvement. DESIGN/SETTINGS/SUBJECTS: A single-site, single-blind, randomized trial of 114 participants diagnosed with fibromyalgia for at least 1 year was performed.
INTERVENTION: Participants were randomized to one of four treatment groups: (1) T/S needles placed in traditional sites with manual needle stimulation (n = 29): (2) T/0 traditional needle location without stimulation (n = 30); (3) N/S needles inserted in nontraditional locations that were not thought to be acupuncture sites, with stimulation (n = 28); and (4) N/0 nontraditional needle location without stimulation (n = 2 7). All groups received treatment once weekly, followed by twice weekly, and finally three times weekly, for a total of 18 treatments. Each increase in frequency was separated by a 2-week washout period.
OUTCOME MEASURES: Pain was assessed by a numerical rating scale, fatigue by the Multi-dimensional Fatigue Inventory, and physical function by the Short Form-36.
RESULTS: Overall pain improvement was noted with 25%-35% of subjects having a clinically significant decrease in pain; however this was not dependent upon "correct" needle stimulation (t = 1.03; p = 0.307) or location (t = 0.76; p = 0.450). An overall dose effect of treatment was observed, with three sessions weekly providing more analgesia than sessions once weekly (t = 2.10; p = 0.039). Among treatment responders, improvements in pain, fatigue, and physical function were highly codependent (all p < or = 0.002).
CONCLUSIONS: Although needle insertion led to analgesia and improvement in other somatic symptoms, correct needle location and stimulation were not crucial.
Martin DP, Sletten CD, Williams BA, Berger IH.
Improvement in fibromyalgia symptoms with acupuncture: results of a randomized controlled trial.
Mayo Clin Proc. 2006 Jun;81(6):749-57. doi: 10.4065/81.6.749.
Abstract/Text
OBJECTIVE: To test the hypothesis that acupuncture improves symptoms of fibromyalgia.
PATIENTS AND METHODS: We conducted a prospective, partially blinded, controlled, randomized clinical trial of patients receiving true acupuncture compared with a control group of patients who received simulated acupuncture. All patients met American College of Rheumatology criteria for fibromyalgia and had tried conservative symptomatic treatments other than acupuncture. We measured symptoms with the Fibromyalgia Impact Questionnaire (FIQ) and the Multidimensional Pain Inventory at baseline, immediately after treatment, and at 1 month and 7 months after treatment. The trial was conducted from May 28, 2002, to August 18, 2003.
RESULTS: Fifty patients participated in the study: 25 in the acupuncture group and 25 in the control group. Total fibromyalgia symptoms, as measured by the FIQ, were significantly improved in the acupuncture group compared with the control group during the study period (P = .01). The largest difference in mean FIQ total scores was observed at 1 month (42.2 vs 34.8 in the control and acupuncture groups, respectively; P = .007). Fatigue and anxiety were the most significantly improved symptoms during the follow-up period. However, activity and physical function levels did not change. Acupuncture was well tolerated, with minimal adverse effects.
CONCLUSION: This study paradigm allows for controlled and blinded clinical trials of acupuncture. We found that acupuncture significantly improved symptoms of fibromyalgia. Symptomatic improvement was not restricted to pain relief and was most significant for fatigue and anxiety.
Deluze C, Bosia L, Zirbs A, Chantraine A, Vischer TL.
Electroacupuncture in fibromyalgia: results of a controlled trial.
BMJ. 1992 Nov 21;305(6864):1249-52. doi: 10.1136/bmj.305.6864.1249.
Abstract/Text
OBJECTIVE: To determine the efficacy of electroacupuncture in patients with fibromyalgia, a syndrome of unknown origin causing diffuse musculoskeletal pain.
DESIGN: Three weeks' randomised study with blinded patients and evaluating physician.
SETTING: University divisions of physical medicine and rehabilitation and rheumatology, Geneva.
PATIENTS: 70 patients (54 women) referred to the division for fibromyalgia as defined by the American College of Rheumatology.
INTERVENTIONS: Patients were randomised to electroacupuncture (n = 36) or a sham procedure (n = 34) by means of an electronic numbers generator.
MAIN OUTCOME MEASURES: Pain threshold, number of analgesic tablets used, regional pain score, pain recorded on visual analogue scale, sleep quality, morning stiffness, and patient's and evaluating physician's appreciation.
RESULTS: Seven of the eight outcome parameters showed a significant improvement in the active treatment group whereas none were improved in the sham treatment group. Differences between the groups were significant for five of the eight outcome measures after treatment.
CONCLUSIONS: Electroacupuncture is effective in relieving symptoms of fibromyalgia. Its potential in long term management should now be studied.
Cao H, Liu J, Lewith GT.
Traditional Chinese Medicine for treatment of fibromyalgia: a systematic review of randomized controlled trials.
J Altern Complement Med. 2010 Apr;16(4):397-409. doi: 10.1089/acm.2009.0599.
Abstract/Text
BACKGROUND: Traditional Chinese Medicine (TCM) is popular for treatment of fibromyalgia (FM) although there is a lack of comprehensive evaluation of current clinical evidence for TCM's therapeutic effect and safety.
OBJECTIVE: To review systematically the beneficial and harmful effects of TCM therapies for FM.
METHODS: We searched six English and Chinese electronic databases for randomized clinical trials (RCTs) on TCM for treatment of FM. Two authors extracted data and assessed the trial quality independently. RevMan 5 software was used for data analyses with an effect estimate presented as mean difference (MD) with a 95% confidence interval (CI).
RESULTS: Twenty-five RCTs were identified with 1516 participants for this review. Seven trials (28%) were evaluated as having a low risk of bias and the remaining trials were identified as being as unclear or having a high risk of bias. Overall, ten trials were eligible for the meta-analysis, and data from remaining 15 trials were synthesized qualitatively. Acupuncture reduced the number of tender points (MD, -3.21; 95% CI -4.23 to -2.11; p < 0.00001, I(2) = 0%), and pain scores compared with conventional medications (MD, -1.78; 95% CI, -2.24 to -1.32; p < 0.00001; I(2) = 0%). Acupuncture showed no significant effect, with a random-effect model, compared with sham acupuncture (MD, -0.55; 95% CI, -1.35-0.24; p = 0.17; I(2) = 69%), on pain reduction. A combination of acupuncture and cupping therapy was better than conventional medications for reducing pain (MD, -1.66; 95% CI, -2.14 to -1.19; p < 0.00001; I(2) = 0%), and for improving depression scores with related to FM (MD, -4.92; 95% CI, -6.49 to -3.34; p < 0.00001; I(2) = 32%). Other individual trials demonstrated positive effects of Chinese herbal medicine on pain reduction compared with conventional medications. There were no serious adverse effects reported that were related to TCM therapies in these trials.
CONCLUSIONS: TCM therapies appear to be effective for treating FM. However, further large, rigorously designed trials are warranted because of insufficient methodological rigor in the included trials.
Zheng C, Zhou T.
Effect of Acupuncture on Pain, Fatigue, Sleep, Physical Function, Stiffness, Well-Being, and Safety in Fibromyalgia: A Systematic Review and Meta-Analysis.
J Pain Res. 2022;15:315-329. doi: 10.2147/JPR.S351320. Epub 2022 Feb 3.
Abstract/Text
PURPOSE: Fibromyalgia (FM) is a syndrome characterized by widespread pain, which caused huge economic and social burden. Acupuncture is often used to manage chronic pain. However, the efficacy of acupuncture in FM is still controversial. This study aimed to systematically review the effects of acupuncture on pain, fatigue, sleep quality, physical function, stiffness, well-being, and safety in FM.
METHODS: We searched databases including PubMed, Embase, the Cochrane Library, Wanfang Database, Chongqing Weipu, and the China National Knowledge Infrastructure from inception to September 2021. Eligible studies included randomized or quasi-randomized controlled studies of acupuncture in patients with FM. Quantitative analysis was conducted using RevMan 5.3 software, and risk assessment was performed according to the Cochrane collaboration tool. Safety was quantitatively analyzed.
RESULTS: A total of 13 articles were searched, of which 12 were analyzed quantitatively. Our meta-analysis found that acupuncture could alleviate pain (SMD: -0.42, 95% CI, -0.66, -0.17, P<0.001, I2=58%) and improve well-being (SMD: -0.86, 95% CI, -1.49, 0.24, P=0.007, I2=85%) at post-treatment. In addition, acupuncture showed long-term effects on reducing pain (P=0.03) and improving well-being (P<0.001). No evidence that acupuncture works on fatigue, sleep quality, physical function, or stiffness was found. No serious adverse events were detected in acupuncture treatment.
CONCLUSION: Moderate quality of evidence supports acupuncture in reducing pain in patients with FM. Therefore, acupuncture is recommended as a treatment for FM.
© 2022 Zheng and Zhou.
Cao CF, Ma KL, Li QL, Luan FJ, Wang QB, Zhang MH, Viswanath O, Myrcik D, Varrassi G, Wang HQ.
Balneotherapy for Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis.
J Clin Med. 2021 Apr 3;10(7). doi: 10.3390/jcm10071493. Epub 2021 Apr 3.
Abstract/Text
(1) Background: The efficiency of balneotherapy (BT) for fibromyalgia syndrome (FMS) remains elusive. (2) Methods: Cochrane Library, EMBASE, MEDLINE, PubMed, Clinicaltrials.gov, and PsycINFO were searched from inception to 31 May 2020. Randomized controlled trials (RCTs) with at least one indicator were included, i.e., pain, Fibromyalgia Impact Questionnaire (FIQ), Tender Points Count (TPC), and Beck's Depression Index (BDI). The outcome was reported as a standardized mean difference (SMD), 95% confidence intervals (CIs), and I2 for heterogeneity at three observational time points. GRADE was used to evaluate the strength of evidence. (3) Results: Amongst 884 citations, 11 RCTs were included (n = 672). Various BT regimens were reported (water types, duration, temperature, and ingredients). BT can benefit FMS with statistically significant improvement at different time points (pain of two weeks, three and six months: SMD = -0.92, -0.45, -0.70; 95% CI (-1.31 to -0.53, -0.73 to -0.16, -1.34 to -0.05); I2 = 54%, 51%, 87%; GRADE: very low, moderate, low; FIQ: SMD = -1.04, -0.64, -0.94; 95% CI (-1.51 to -0.57, -0.95 to -0.33, -1.55 to -0.34); I2 = 76%, 62%, 85%; GRADE: low, low, very low; TPC at two weeks and three months: SMD = -0.94, -0.47; 95% CI (-1.69 to -0.18, -0.71 to -0.22); I2 = 81%, 0; GRADE: very low, moderate; BDI at six months: SMD = -0.45; 95% CI (-0.73 to -0.17); I2 = 0; GRADE: moderate). There was no statistically significant effect for the TPC and BDI at the remaining time points (TPC at six months: SMD = -0.89; 95% CI (-1.85 to 0.07); I2 = 91%; GRADE: very low; BDI at two weeks and three months: SMD = -0.35, -0.23; 95% CI (-0.73 to 0.04, -0.64 to 0.17); I2 = 24%, 60%; GRADE: moderate, low). (4) Conclusions: Very low to moderate evidence indicates that BT can benefit FMS in pain and quality-of-life improvement, whereas tenderness and depression improvement varies at time phases. Established BT regimens with a large sample size and longer observation are needed.
Matsushita K, Masuda A, Tei C.
Efficacy of Waon therapy for fibromyalgia.
Intern Med. 2008;47(16):1473-6. doi: 10.2169/internalmedicine.47.1054. Epub 2008 Aug 15.
Abstract/Text
OBJECTIVE: Fibromyalgia syndrome (FMS) is a chronic syndrome characterized by widespread pain with tenderness in specific areas. We examined the applicability of Waon therapy (soothing warmth therapy) as a new method of pain treatment in patients with FMS.
METHODS: Thirteen female FMS patients (mean age, 45.2+/-15.5 years old; range, 25-75) who fulfilled the criteria of the American College of Rheumatology participated in this study. Patients received Waon therapy once per day for 2 or 5 days/week. The patients were placed in the supine or sitting position in a far infrared-ray dry sauna maintained at an even temperature of 60 degrees C for 15 minutes, and then transferred to a room maintained at 26-27 degrees C where they were covered with a blanket from the neck down to keep them warm for 30 minutes. Reductions in subjective pain and symptoms were determined using the pain visual analog scale (VAS) and fibromyalgia impact questionnaire (FIQ).
RESULTS: All patients experienced a significant reduction in pain by about half after the first session of Waon therapy (11-70%), and the effect of Waon therapy became stable (20-78%) after 10 treatments. Pain VAS and FIQ symptom scores were significantly (p<0.01) decreased after Waon therapy and remained low throughout the observation period.
CONCLUSION: Waon therapy is effective for the treatment of fibromyalgia syndrome.
Azad KA, Alam MN, Haq SA, Nahar S, Chowdhury MA, Ali SM, Ullah AK.
Vegetarian diet in the treatment of fibromyalgia.
Bangladesh Med Res Counc Bull. 2000 Aug;26(2):41-7.
Abstract/Text
Brain tryptophan is low in fibromyalgia. Intake of protein rich in large neutral amino acids is reported to lower brain tryptophan. This study was undertaken to assess whether any reduction of such proteins by exclusion of animal protein from the diet reduced pain and morbidity in fibromyalgia patients. It was an open, randomized controlled trial. 37 subjects with fibromyalgia were enrolled in the vegetarian diet and 41 in the amitriptyline groups. The outcome was assessed with the help of frequencies of fatigue, insomnia & non-restorative sleep, pain score on a 10-point VAS and tender point count. Fatigue, insomnia and non-restorative sleep were present in 41, 26 and 32 subjects before and in 3, 0 and 0 subjects respectively at six weeks of treatment in the amitriptyline group. The pain score and tender point count were 6.2 +/- 1.9 & 16.1 +/- 2.3 before and 2.3 +/- 1.3 & 6.4 +/- 3.0 after treatment. All these differences were significant (P < 0.001). In the vegetarian diet group, fatigue, insomnia and non-restorative sleep were present in 36, 24 and 27 subjects before and in 34, 29 and 29 subjects at six weeks of treatment. The pain score and tender point count were 5.7 +/- 1.8 and 15.7 +/- 2.4 before and 5.0 +/- 1.8 & 14.7 +/- 3.6 after treatment. All these differences were insignificant except that in the pain score. The decrease in the pain score, though significant, was much smaller than that in the amitriptyline group. So, it may be concluded that vegetarian diet is a poor option in the treatment of fibromyalgia.
Lowry E, Marley J, McVeigh JG, McSorley E, Allsopp P, Kerr D.
Dietary Interventions in the Management of Fibromyalgia: A Systematic Review and Best-Evidence Synthesis.
Nutrients. 2020 Aug 31;12(9). doi: 10.3390/nu12092664. Epub 2020 Aug 31.
Abstract/Text
Fibromyalgia syndrome (FMS) is characterised by chronic widespread pain alongside fatigue, poor sleep quality and numerous comorbidities. It is estimated to have a worldwide prevalence of 1.78%, with a predominance in females. Treatment interventions for fibromyalgia have limited success, leading to many patients seeking alternative forms of treatment, including modifications to their diet and lifestyle. The effectiveness of dietary changes in fibromyalgia has not been widely researched or evaluated. This systematic review identified twenty-two studies, including 18 randomised control trials (RCTs) and four cohort studies which were eligible for inclusion. In total these studies investigated 17 different nutritional interventions. Significant improvements in reported pain were observed for those following a vegan diet, as well as with the low fermentable oligo di-mono-saccharides and polyols (FODMAP) diets. Supplementation with Chlorella green algae, coenzyme Q10, acetyl-l-carnitine or a combination of vitamin C and E significantly improved measures of pain. Interpretation of these studies was limited due to the frequent poor quality of the study design, the wide heterogeneity between studies, the small sample size and a high degree of bias. Therefore, there is insufficient evidence to recommend any one particular nutritional intervention for the management of fibromyalgia and further research is needed.
Michalsen A, Li C, Kaiser K, Lüdtke R, Meier L, Stange R, Kessler C.
In-Patient Treatment of Fibromyalgia: A Controlled Nonrandomized Comparison of Conventional Medicine versus Integrative Medicine including Fasting Therapy.
Evid Based Complement Alternat Med. 2013;2013:908610. doi: 10.1155/2013/908610. Epub 2013 Jan 23.
Abstract/Text
Fibromyalgia poses a challenge for therapy. Recent guidelines suggest that fibromyalgia should be treated within a multidisciplinary therapy approach. No data are available that evaluated multimodal treatment strategies of Integrative Medicine (IM). We conducted a controlled, nonrandomized pilot study that compared two inpatient treatment strategies, an IM approach that included fasting therapy and a conventional rheumatology (CM) approach. IM used fasting cure and Mind-Body-Medicine as specific methods. Of 48 included consecutive patients, 28 were treated with IM, 20 with CM. Primary outcome was change in the Fibromyalgia Impact Questionnaire (FIQ) score after the 2-week hospital stay. Secondary outcomes included scores of pain, depression, anxiety, and well being. Assessments were repeated after 12 weeks. At 2 weeks, there were significant improvements in the FIQ (P < 0.014) and for most of secondary outcomes for the IM group compared to the CM group. The beneficial effects for the IM approach were reduced after 12 weeks and no longer statistically significant with the exception of anxiety. Findings indicate that a multimodal IM treatment with fasting therapy might be superior to CM in the short term and not inferior in the mid term. Longer-term studies are warranted to assess the clinical impact of integrative multimodal treatment in fibromyalgia.
Nüesch E, Häuser W, Bernardy K, Barth J, Jüni P.
Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis.
Ann Rheum Dis. 2013 Jun;72(6):955-62. doi: 10.1136/annrheumdis-2011-201249. Epub 2012 Jun 27.
Abstract/Text
OBJECTIVES: To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS).
METHODS: Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms.
RESULTS: 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT.
CONCLUSIONS: Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.
Bernardy K, Klose P, Busch AJ, Choy EH, Häuser W.
Cognitive behavioural therapies for fibromyalgia.
Cochrane Database Syst Rev. 2013 Sep 10;2013(9):CD009796. doi: 10.1002/14651858.CD009796.pub2. Epub 2013 Sep 10.
Abstract/Text
BACKGROUND: Fibromyalgia (FM) is a clinically well-defined chronic condition of unknown aetiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. Patients often report high disability levels and negative mood. Psychotherapies focus on reducing key symptoms, improving daily functioning, mood and sense of personal control over pain.
OBJECTIVES: To assess the benefits and harms of cognitive behavioural therapies (CBTs) for treating FM at end of treatment and at long-term (at least six months) follow-up.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE (1966 to 28 August 2013), PsycINFO (1966 to 28 August 2013) and SCOPUS (1980 to 28 August 2013). We searched http://www.clinicaltrials.gov (web site of the US National Institutes of Health) and the World Health Organization Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/) for ongoing trials (last search 28 August,2013), and the reference lists of reviewed articles.
SELECTION CRITERIA: We selected randomised controlled trials of CBTs with children, adolescents and adults diagnosed with FM.
DATA COLLECTION AND ANALYSIS: The data of all included studies were extracted and the risks of bias of the studies were assessed independently by two review authors. Discrepancies were resolved by discussion.
MAIN RESULTS: Twenty-three studies with 24 study arms with CBTs were included. A total of 2031 patients were included; 1073 patients in CBT groups and 958 patients in control groups. Only two studies were without any risk of bias. The GRADE quality of evidence of the studies was low. CBTs were superior to controls in reducing pain at end of treatment by 0.5 points on a scale of 0 to 10 (standardised mean difference (SMD) - 0.29; 95% confidence interval (CI) -0.49 to -0.17) and by 0.6 points at long-term follow-up (median 6 months) (SMD -0.40; 95% CI -0.62 to -0.17); in reducing negative mood at end of treatment by 0.7 points on a scale of 0 to 10 (SMD - 0.33; 95% CI -0.49 to -0.17) and by 1.3 points at long-term follow-up (median 6 months) (SMD -0.43; 95% CI -0.75 to -0.11); and in reducing disability at end of treatment by 0.7 points on a scale of 0 to 10 (SMD - 0.30; 95% CI -0.51 to -0.08) and at long-term follow-up (median 6 months) by 1.2 points (SMD -0.52; 95% CI -0.86 to -0.18). There was no statistically significant difference in dropout rates for any reasons between CBTs and controls (risk ratio (RR) 0.94; 95% CI 0.65 to 1.35).
AUTHORS' CONCLUSIONS: CBTs provided a small incremental benefit over control interventions in reducing pain, negative mood and disability at the end of treatment and at long-term follow-up. The dropout rates due to any reason did not differ between CBTs and controls.
Busch AJ, Barber KA, Overend TJ, Peloso PM, Schachter CL.
Exercise for treating fibromyalgia syndrome.
Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003786. doi: 10.1002/14651858.CD003786.pub2. Epub 2007 Oct 17.
Abstract/Text
BACKGROUND: Fibromyalgia (FMS) is a syndrome expressed by chronic widespread body pain which leads to reduced physical function and frequent use of health care services. Exercise training is commonly recommended as a treatment. This is an update of a review published in Issue 2, 2002.
OBJECTIVES: The primary objective of this systematic review was to evaluate the effects of exercise training including cardiorespiratory (aerobic), muscle strengthening, and/or flexibility exercise on global well-being, selected signs and symptoms, and physical function in individuals with FMS.
SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, SportDiscus, PubMed, PEDro, and the Cochrane Central Register for Controlled Trials (CENTRAL, Issue 3, 2005) up to and including July 2005. We also reviewed reference lists from reviews and meta-analyses of treatment studies.
SELECTION CRITERIA: Randomized trials focused on cardiorespiratory endurance, muscle strength and/or flexibility as treatment for FMS were selected.
DATA COLLECTION AND ANALYSIS: Two of four reviewers independently extracted data for each study. All discrepancies were rechecked and consensus achieved by discussion. Methodological quality was assessed by two instruments: the van Tulder and the Jadad methodological quality criteria. We used the American College of Sport Medicine (ACSM) guidelines to evaluate whether interventions had provided a training stimulus that would effect changes in physical fitness. Due to significant clinical heterogeneity among the studies we were only able to meta-analyze six aerobic-only studies and two strength-only studies.
MAIN RESULTS: There were a total of 2276 subjects across the 34 included studies; 1264 subjects were assigned to exercise interventions. The 34 studies comprised 47 interventions that included exercise. Effects of several disparate interventions on global well-being, selected signs and symptoms, and physical function in individuals with FMS were summarized using standardized mean differences (SMD). There is moderate quality evidence that aerobic-only exercise training at recommended intensity levels has positive effects global well-being (SMD 0.44, 95% confidence interval (CI 0.13 to 0.75) and physical function (SMD 0.68, 95% CI 0.41 to 0.95) and possibly on pain (SMD 0.94, 95% CI -0.15 to 2.03) and tender points (SMD 0.26, 95% CI -0.28 to 0.79). Strength and flexibility remain under-evaluated.
AUTHORS' CONCLUSIONS: There is 'gold' level evidence (www.cochranemsk.org) that supervised aerobic exercise training has beneficial effects on physical capacity and FMS symptoms. Strength training may also have benefits on some FMS symptoms. Further studies on muscle strengthening and flexibility are needed. Research on the long-term benefit of exercise for FMS is needed.
Fraioli A, Grassi M, Mennuni G, Geraci A, Petraccia L, Fontana M, Conte S, Serio A.
Clinical researches on the efficacy of spa therapy in fibromyalgia. A systematic review.
Ann Ist Super Sanita. 2013;49(2):219-29. doi: 10.4415/ANN_13_02_13.
Abstract/Text
BACKGROUND: Fibromyalgia is characterized by chronic widespread pain, tenderness at muscle and tendon insertions point when digital pressure is applied, sleep disorders, chronic fatigue, depressive episodes, anxiety, and other functional somatic syndromes.
OBJECTIVE: The aim of this study was to determine whether balneotherapy with mineral waters and mineral-water containing mud is effective in the management of fibromyalgia.
METHODS: We conducted a systematic review of the literature regarding spa therapy in the treatment of the fibromyalgia. We searched many databases for articles published between 2000 and 2012 and we selected 7 studies among 65 articles retrieved. A total of 142 patients received balneotherapy and 129 were controls.
CONCLUSION: Study data confirms that spa therapy could improve the symptoms of fibromyalgia including pain, depression and minor symptoms.
Deare JC, Zheng Z, Xue CC, Liu JP, Shang J, Scott SW, Littlejohn G.
Acupuncture for treating fibromyalgia.
Cochrane Database Syst Rev. 2013 May 31;2013(5):CD007070. doi: 10.1002/14651858.CD007070.pub2. Epub 2013 May 31.
Abstract/Text
BACKGROUND: One in five fibromyalgia sufferers use acupuncture treatment within two years of diagnosis.
OBJECTIVES: To examine the benefits and safety of acupuncture treatment for fibromyalgia.
SEARCH METHODS: We searched CENTRAL, PubMed, EMBASE, CINAHL, National Research Register, HSR Project and Current Contents, as well as the Chinese databases VIP and Wangfang to January 2012 with no language restrictions.
SELECTION CRITERIA: Randomised and quasi-randomised studies evaluating any type of invasive acupuncture for fibromyalgia diagnosed according to the American College of Rheumatology (ACR) criteria, and reporting any main outcome: pain, physical function, fatigue, sleep, total well-being, stiffness and adverse events.
DATA COLLECTION AND ANALYSIS: Two author pairs selected trials, extracted data and assessed risk of bias. Treatment effects were reported as standardised mean differences (SMD) and 95% confidence intervals (CI) for continuous outcomes using different measurement tools (pain, physical function, fatigue, sleep, total well-being and stiffness) and risk ratio (RR) and 95% CI for dichotomous outcomes (adverse events). We pooled data using the random-effects model.
MAIN RESULTS: Nine trials (395 participants) were included. All studies except one were at low risk of selection bias; five were at risk of selective reporting bias (favouring either treatment group); two were subject to attrition bias (favouring acupuncture); three were subject to performance bias (favouring acupuncture) and one to detection bias (favouring acupuncture). Three studies utilised electro-acupuncture (EA) with the remainder using manual acupuncture (MA) without electrical stimulation. All studies used 'formula acupuncture' except for one, which used trigger points.Low quality evidence from one study (13 participants) showed EA improved symptoms with no adverse events at one month following treatment. Mean pain in the non-treatment control group was 70 points on a 100 point scale; EA reduced pain by a mean of 22 points (95% confidence interval (CI) 4 to 41), or 22% absolute improvement. Control group global well-being was 66.5 points on a 100 point scale; EA improved well-being by a mean of 15 points (95% CI 5 to 26 points). Control group stiffness was 4.8 points on a 0 to 10 point; EA reduced stiffness by a mean of 0.9 points (95% CI 0.1 to 2 points; absolute reduction 9%, 95% CI 4% to 16%). Fatigue was 4.5 points (10 point scale) without treatment; EA reduced fatigue by a mean of 1 point (95% CI 0.22 to 2 points), absolute reduction 11% (2% to 20%). There was no difference in sleep quality (MD 0.4 points, 95% CI -1 to 0.21 points, 10 point scale), and physical function was not reported.Moderate quality evidence from six studies (286 participants) indicated that acupuncture (EA or MA) was no better than sham acupuncture, except for less stiffness at one month. Subgroup analysis of two studies (104 participants) indicated benefits of EA. Mean pain was 70 points on 0 to 100 point scale with sham treatment; EA reduced pain by 13% (5% to 22%); (SMD -0.63, 95% CI -1.02 to -0.23). Global well-being was 5.2 points on a 10 point scale with sham treatment; EA improved well-being: SMD 0.65, 95% CI 0.26 to 1.05; absolute improvement 11% (4% to 17%). EA improved sleep, from 3 points on a 0 to 10 point scale in the sham group: SMD 0.40 (95% CI 0.01 to 0.79); absolute improvement 8% (0.2% to 16%). Low-quality evidence from one study suggested that MA group resulted in poorer physical function: mean function in the sham group was 28 points (100 point scale); treatment worsened function by a mean of 6 points (95% CI -10.9 to -0.7). Low-quality evidence from three trials (289 participants) suggested no difference in adverse events between real (9%) and sham acupuncture (35%); RR 0.44 (95% CI 0.12 to 1.63).Moderate quality evidence from one study (58 participants) found that compared with standard therapy alone (antidepressants and exercise), adjunct acupuncture therapy reduced pain at one month after treatment: mean pain was 8 points on a 0 to 10 point scale in the standard therapy group; treatment reduced pain by 3 points (95% CI -3.9 to -2.1), an absolute reduction of 30% (21% to 39%). Two people treated with acupuncture reported adverse events; there were none in the control group (RR 3.57; 95% CI 0.18 to 71.21). Global well-being, sleep, fatigue and stiffness were not reported. Physical function data were not usable.Low quality evidence from one study (38 participants) showed a short-term benefit of acupuncture over antidepressants in pain relief: mean pain was 29 points (0 to 100 point scale) in the antidepressant group; acupuncture reduced pain by 17 points (95% CI -24.1 to -10.5). Other outcomes or adverse events were not reported.Moderate-quality evidence from one study (41 participants) indicated that deep needling with or without deqi did not differ in pain, fatigue, function or adverse events. Other outcomes were not reported.Four studies reported no differences between acupuncture and control or other treatments described at six to seven months follow-up.No serious adverse events were reported, but there were insufficient adverse events to be certain of the risks.
AUTHORS' CONCLUSIONS: There is low to moderate-level evidence that compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with fibromyalgia. There is moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture in reducing pain or fatigue, or improving sleep or global well-being. EA is probably better than MA for pain and stiffness reduction and improvement of global well-being, sleep and fatigue. The effect lasts up to one month, but is not maintained at six months follow-up. MA probably does not improve pain or physical functioning. Acupuncture appears safe. People with fibromyalgia may consider using EA alone or with exercise and medication. The small sample size, scarcity of studies for each comparison, lack of an ideal sham acupuncture weaken the level of evidence and its clinical implications. Larger studies are warranted.
Senna MK, Sallam RA, Ashour HS, Elarman M.
Effect of weight reduction on the quality of life in obese patients with fibromyalgia syndrome: a randomized controlled trial.
Clin Rheumatol. 2012 Nov;31(11):1591-7. doi: 10.1007/s10067-012-2053-x. Epub 2012 Sep 5.
Abstract/Text
The aim of the study was to examine whether weight reduction can result in improvement of fibromyalgia impact questionnaire (FIQ) in the patients with fibromyalgia syndrome (FMS). This study was a randomized controlled trial. Obese patients with fibromyalgia were randomly assigned to 6-month dietary weight loss (n = 41) and no weight loss (n = 42) groups. Patients were assessed at baseline and at 6 months. The primary outcome measure was FIQ. Secondary measures included the tender point (TP) examination, Beck Depression Inventory-II, and Pittsburg Sleep Quality Index. Compared to the control group, patients who underwent weight reduction obtained significantly better FIQ (p = 0.007), lower mean TP count (p = 0.015), and lower mean TP pain rating in the lower body (p < 0.001). Patients who lost weight had less depression and better sleep quality than the controls. Patients who lost weight had significantly lower interleukin 6 and C-reactive protein levels than those in the control group (p = 0.034 and p = 0.007, respectively). Weight loss in obese patients with FMS leads to significant improvement in the quality of life as shown by the decrease in the FIQ score. Depression, sleep quality, and tender point count are also significantly improved by weight loss in obese patients with fibromyalgia. Our results suggest that weight reduction should be a part of fibromyalgia treatment.
Alvarez Lario B, Alonso Valdivielso JL, Alegre López J, Martel Soteres C, Viejo Bañuelos JL, Marañón Cabello A.
Fibromyalgia syndrome: overnight falls in arterial oxygen saturation.
Am J Med. 1996 Jul;101(1):54-60. doi: 10.1016/s0002-9343(96)00067-8.
Abstract/Text
PURPOSE: Sleep alterations and muscular changes suggesting hypoxia have been reported in fibromyalgia syndrome (FS) pathophysiology. We tested the hypothesis that patients with FS show falls in the oxygen saturation of hemoglobin in arterial blood (SaO2%) during sleep.
PATIENTS AND METHODS: Overnight SaO2% was measured by digital pulse oximetry in 28 randomly selected women who met 1990 American College of Rheumatology criteria for the diagnosis of FS and 15 similar controls. Considering the results of pulse oximetry and in order to evaluate the possible presence of a sleep apnea syndrome (SAS) as the reason for the nocturnal desaturations, the Epworth Sleepiness Scale (ESS) was mailed to the patients and controls. Patients and controls who had a score higher than 10 on the ESS underwent a polysomnographic study.
RESULTS: Patients with FS showed lower overnight minimum SaO2% (86.8 +/- 1.3 versus 90.7 +/- 0.9 in controls, P < 0.05), greater number of desaturations (8.3 +/- 1.8 versus 2.7 +/- 0.8 in controls, P < 0.05) and more desaturations/hour (1.3 +/- versus 0.4 +/- 0.1 in controls, P < 0.05), more night minutes in SaO2% < 92% (56.3 +/- 12.9 versus 9.1 +/- 3.8 in controls, P < 0.01) and more minutes in SaO2% < 90% (14.7 +/- 3.7 versus 2.4 +/- 1.0 in controls, P < 0.05). There were no differences between patients with FS and controls in ESS scores. Five patients (19.2%) in the FS group and 2 (15.4%) in the control group had ESS scores higher than 10. One patient had 1 control subject showed on apnea-plus-hypopnea index higher than 5 (13 and 9, respectively) in polysomnographic study.
CONCLUSIONS: Patients with FS showed small overnight falls in SaO2% and spent more time during the night in SaO2% below 92% and 90% than did the control group. These alterations that, as a whole, are not due to the presence of an associated SAS could be important in FS musculoskeletal pathophysiology.
Pamuk ON, Dönmez S, Cakir N.
The frequency of smoking in fibromyalgia patients and its association with symptoms.
Rheumatol Int. 2009 Sep;29(11):1311-4. doi: 10.1007/s00296-009-0851-5. Epub 2009 Jan 20.
Abstract/Text
The objective of the study was to determine the frequency of smoking in fibromyalgia (FM) and rheumatoid arthritis (RA) patients and investigate its association with the symptoms of FM. We included age-matched 302 FM (289 F, 13 M), and 115 (105 F, 10 M) RA patients. All patients were questioned about smoking and the severity of their chronic widespread pain (CWP) and symptoms of FM by using a visual analog scale (VAS, 0-10) and FM impact questionnaire. In addition, patients were asked questions about depression and anxiety. The frequency of smoking in FM patients (77 subjects, 25.5%) tended to be higher than in RA patients (19 subjects, 16.5%) (P = 0.05). When the features of smoker FM patients were compared to others, it was observed that the frequencies of subjects with an education duration >9 years (P < 0.001) and subjects with an history of psychiatric therapy (P = 0.01) and alcohol consumption (P = 0.013) were higher. The mean age of FM patients with smoking (P = 0.002) was lower; the duration of FM (P = 0.024) was shorter; and the scores of CWP severity (P = 0.05), unrestorative sleepiness (P = 0.017), paresthesia (P = 0.038) and anxiety-depression (P = 0.007) were higher. An important proportion of FM patients, nearly one-fourth, were re-smokers. Smoker FM patients had higher education level, and the severity of their FM-related symptoms like CWP and their anxiety-depression scores were higher.
C薬物療法．厚労省慢性の痛み政策研究事業研究班監修、国内慢性疼痛関連10学会合同編集：慢性疼痛診療ガイドライン．真興交易（株）医書出版部、東京、2021、p67-68.
Deeks ED.
Mirogabalin: First Global Approval.
Drugs. 2019 Mar;79(4):463-468. doi: 10.1007/s40265-019-01070-8.
Abstract/Text
Mirogabalin besylate (hereafter mirogabalin) [Tarlige®] is an orally administered gabapentinoid developed by Daiichi Sankyo for the treatment of peripheral neuropathic pain (PNP), including diabetic PNP and post-herpetic neuralgia. The drug binds to and modulates the α2δ-1 subunit of the voltage-gated calcium channels widely found in the nervous system in areas that mediate pain transmission and processing. Mirogabalin has a unique binding profile and long duration of action. The drug is approved in Japan for the treatment of PNP and is in clinical development for this indication elsewhere in Asia. Clinical development of the drug for fibromyalgia pain was discontinued in the USA and EU after the primary endpoint was not met in phase 3 trials. No recent reports of development have been identified for PNP in the USA or India or for fibromyalgia pain in Australia, India, New Zealand, Russia, Argentina, Belarus, Chile, Colombia, Israel, Mexico, Switzerland, Canada, Serbia or South Africa. This article summarizes the milestones in the development of mirogabalin leading to this first approval for PNP.
